BRI 7-8/14 STI-March-Quark4

PREMIER NEWS SOURCE FOR LIFE SCIENCE RESEARCHERS WORLDWIDE ISSN 1939-4470 Vol.19 No.4 • 7-8/2014

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Nanoparticle Created Mass Spectrometry Technology Maps Graphene Could Reshape For Cancer Therapy Chemicals as They Migrate into Skin Neurological Treatment physicist working to create a lu- mass spectrometry technique The study’s findings were pub- raphene, a two-dimensional AAminescent nanoparticle to use AAgaining acceptance for medical lished April 28, 2014, in the Journal GG(2D) crystalline allotrope of in security-related radiation detec- applications such as imaging tumor of the American Chemical Society. carbon, may lead to new advances tion may have instead developed a surfaces can also be used to analyze Stanford University (Stanford, CA, in several areas of neurosurgery, ac- new tool for photodynamic cancer the migration of small-molecule com- USA; www.stanford.edu) chemistry cording to a new topic review. Re- therapy. Wei Chen, professor of pounds applied to the skin. Because Professors Richard N. Zare and searchers at the University of Illinois physics and co-director of University skin is such a complicated organ, the Justin Du Bois, postdoc Livia S. College of Medicine (Peoria, USA; of Texas (UT) at Arlington (USA; technology could be a helpful for de- Eberlin, graduate student John V. www.peoria.medicine.uic.edu) and www.uta.edu) Center for Security veloping transdermal drugs. Mulcahy, and colleagues revealed Invision Health Brain and Spine Cont’d on page 5 Cont’d on page 6 Cont’d on page 7 Light-Activated Neurons Nature Bank Technique Restore Paralyzed Muscles Expands Horizons of new approach has been devel- AAoped to synthetically control Drug Discovery muscles using light, with the hope of restoring function to muscles par- ustralian researchers have de- alyzed by disorders such as spinal Aveloped an NMR screening cord injury and motor neuron dis- process for identifying natural ease. The technique involves trans- compounds that could lead to planting specially designed motor widespread development of innovative therapeutic agents. The neurons created from stem cells into process is based on investigating Cont’d on page 3 an extensive Nature Bank incorpo- rating over 45,000 samples of plants and marine invertebrates, INSIDE Latest Advances & Applications in: 200,000 semipurified fractions, 3,250 pure compounds and 600 Genomics naturally occurring fragments. Image: Prof. Ronald Quinn asserts the new technique could be used to treat Proteomics See article on page 2 a variety of conditions in the future

Image: Courtesy of Griffith University Drug Discovery

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Identify LinkXpress ® codes of 1 Restoring Effectiveness Genetic Brain Disorder DAILY BIO RESEARCH NEWS interest as you read magazine Of Older Antibiotics Found in Humans Click on LinkXpress.com GLOBETECH MEDIA 2 to reach reader service portal ethicillin-resistant Staphylococ- newly identified genetic disorder MMcus aureus (MRSA), a complex of AAlinked to the degeneration of the Mark code(s) of interest on multidrug-resistant Gram-positive bacte- central and peripheral nervous sys- 3 ® Scan with LinkXpress inquiry matrix rial strains, has proven especially prob- tems in humans, in addition to its the lematic in both hospital and community genetic cause, has been reported by re- Smartphone If your subscription settings. These bacteria have become searchers. By performing DNA se- to Access is not renewed every 12 months drug resistant by deactivating conven- quencing of more than 4,000 families your Free Subscription may be Latest News automatically discontinued tional beta-lactam antibiotics, including affected by neurologic difficulties, the Cont’d on page 6 Cont’d on page 4 Bio Research International for latest news updates visit www.BiotechDaily.com Nature Bank Technique Expands Horizons of Drug Discovery ustralian researchers have developed a new we discovered through this process has demonstrated cility and using the NMR technique trying to visu- AAtool for finding natural compounds that could a response in Parkinson’s disease cells.” alize all the small molecules which could meet the form the foundation of innovative therapeutic The findings were published online April 15, requirements for a potential new drug. “The idea agents. 2014, in the chemistry journal Angewandte was to look at patterns of data and identify unusual The corresponding author, Prof. Ronald Quinn Chemie. The first author Dr. Tanja Grkovic said the or unique sets. We followed one such pattern and AM from Griffith University’s Eskitis Institute for screening process involves nuclear magnetic reso- isolated a natural product with a novel skeleton Drug Discovery (Brisbane, Australia; www.griffith. nance (NMR) spectroscopy; a highly sensitive in- which has turned out to be a molecule which was edu.au/science-aviation/eskitis-institute), reported strument through which it is possible to see natural completely unknown previously.” that testing the new process on a marine sponge had products weighing as little as 20 micrograms. The Griffith Nature Bank is a novel drug discov- delivered not only validation that the system is suc- “When you are searching for nature-derived mole- ery resource based on natural products found in cessful, but also a potential lead in the fight against cules, the jackpot is finding something that nobody China, Australia, and Papua New Guinea. It com- Parkinson’s disease. “We have found a new screening has ever seen before and rather than just a variation prises more than 45,000 samples of plants and ma- method which allows us to identify novel molecules on a known theme,” Dr. Grkovic said. “We began rine invertebrates, 200,000 semipurified fractions, drawn from nature to test for biological activity,” Prof. the project by selecting 20 marine sponge samples 3,250 pure compounds and over 600 naturally oc- Quinn said. “As it happens, the first new compound randomly from Griffith University's Nature Bank fa- curring fragments. This NMR screening process provides a new way of searching all those natural samples stored in the Griffith Na- ture Bank and uncovering the potential biological activity of the compounds within them. Deputy director of the Eskitis Institute and coauthor of the paper, Assoc. Prof. George Mellick, is a specialist researcher in neurodegenerative diseases such as Parkin- son’s disease. He is excited by the research prospects this new molecule may provide. “What is very intriguing about this novel natural product is that, while we have found it has an effect on cells sourced from a Parkinson’s patient, it showed a different biological activity on cells from healthy individuals,” Assoc. Prof. Mellick said. “This provides us with a new tool to study the fundamental biology of Parkinson’s and to get a better understanding of the cellular processes involved in the development of this disease.” The Parkinson’s response is only the beginning, according to the scientists. “This new research technique opens the door to unlimited opportunities, both in terms of chemistry and biology research at Eskitis, as we continue the search for new therapies against disease,” Prof. Quinn said.

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Bio Research International LINKXPRESS COM BRI-08-14 102 July-August/2014 2 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International Light-Activated Neurons Restore Paralyzed Muscles cont’d from cover created from stem cells by Dr. Ivo Lieberam of the damaged nerve branches. These motor neurons MRC Center for Developmental Neurobiology, are devised to react to pulses of blue light, allow- King’s College London. “We custom-tailored em- ing researches to customize muscle control by ad- bryonic stem cells so that motor neurons derived justing the duration, intensity, and frequency of from them can function as part of the muscle the light pulses. pacemaker device,” said Dr. Lieberam, who co-led In the study published April 2014 in Science, the study. “First, we equipped the cells with a mo- scientists from University College London lecular light sensor. This enables us to control mo- (UCL; UK; www.ucl.ac.uk) and King’s College tor neurons with blue light flashes. We then built London (UK; www.kcl.ac.uk) demonstrated the a survival gene into them, which helps the stem- Image: A new technique using light on stem cell-de- technology in lab mice in which the nerves that cell motor neurons to stay alive when they are rived motor neurons could potentially restore function to paralyzed muscles (Photo courtesy of Dr. Bar- supply muscles in the hind legs were injured. transplanted inside the injured nerve and allows ney Bryson / University College London Institute of They showed that the transplanted stem cell-de- them to grow to connect to muscle.” Neurology). rived motor neurons grew along the injured nerves to connect effectively with the paralyzed muscles, which could then be controlled by pulses of blue light. “Following the new procedure, we saw previously paralyzed leg muscles start to function,” noted Prof. Linda Greensmith of the MRC Center for Neuromuscular Diseases at UCL’s Insti- tute of Neurology, who co-led the study. “This strategy has significant advantages over existing techniques that use electricity to stimulate nerves, which can be painful and often results in rapid muscle fatigue. Moreover, if the existing motor neurons are lost due to injury or disease, electrical stimula- tion of nerves is rendered useless as these too are lost.” Muscles are typically controlled by motor neurons, which are specialized nerve cells within the brain and spinal cord. These neurons relay signals from the brain to muscles to initiate motor functions such as walking, standing and even breathing. Howev- er, motor neurons can become damaged in motor neuron disease or following spinal cord injuries, causing permanent loss of muscle function resulting in paralysis. “This new technique represents a means to restore the function of specific muscles following paralyzing neurological injuries or disease,” clarified Prof. Greensmith. “Within the next five years or so, we hope to un- dertake the steps that are necessary to take this ground-breaking approach into human trials, potentially to develop treatments for patients with motor neuron disease, many of whom eventually lose the ability to breathe, as their diaphragm muscles gradually become paralyzed. We eventually hope to use our method to create a sort of optical pacemaker for the diaphragm to keep these patients breathing.” The light-responsive motor neurons that made the technique possible were

Bio Research International 3 July-August/2014 LINKXPRESS COM BRI-08-14 103 Bio Research International Genetic Brain Disorder Found in Humans www.BiotechDaily.com cont’d from cover A GLOBETECH PUBLICATION™ two teams of investigators in- HospiMedica International • HospiMedica en Español • HospiMedica China dependently discovered that a LabMedica International • LabMedica en Español • LabMedica China Medical Imaging International • Bio Research International • Medimaging.net disease marked by reduced HospiMedica.com • LabMedica.com • BiotechDaily.com • TradeMed.com brain size and sensory and motor defects is caused by a muta- Dan Gueron Publisher tion in a gene called CLP1 Jill Roberge Editorial Director (cleavage and polyadenylation Jerry Slutzky, PhD News Editor factor I), which is known to Joseph Ciprut Assistant Editor regulate tRNA metabolism in Brenda Silva New Products Editor cells. Doris Mendieta Regional Director The news findings were re- Renata Castro Regional Director ported in the April 24, 2014 is- Paul Mills Regional Director sue of the journal Cell. The Dr. Jutta Ciolek Regional Director findings were made by two in- Christina Chang Regional Director dependent but collaborative Carolyn Moody Business Development Director scientific teams, one based pri- Arda Turac Production Director marily at Baylor College of Elif Erkan Reader Service Manager Medicine (Houston, TX, USA; HOW TO CONTACT US www.bcm.edu) and the Austri- an Academy of Sciences (Vien- Subscriptions: www.LinkXpress.com na, Austria; www.oeaw.ac.at), Send Press Releases to: [email protected] the other at the University of Advertising & Ad Material: [email protected] California (UC), San Diego Other Contacts: [email protected] School of Medicine (USA; http://ucsd.edu), the might help us to protect motor neurons from dy- Academic Medical Center (AMC; Amsterdam, ing, such as in Lou Gehrig’s disease,” said Dr. ADVERTISING SALES OFFICES The Netherlands; www.amc.nl), and Yale Univer- Penninger, scientific director of the Institute of USA 450 N Park Rd, Suite 503, Hollywood, FL 33021 sity School of Medicine (New Haven, CT, USA; Molecular Biotechnology of the Austrian Acade- [email protected] Tel: (1) 954-893-0003 http://medicine.yale.edu). my of Sciences. GERMANY, AUSTRIA, EASTERN EUR. Bad Neustadt, Germany Clues into this rare disorder, according to the The CLP1 protein plays an important role in [email protected] Tel: (49) 9771-3528 researchers, may have important implications generating mature, functional molecules called UK, BENELUX, FRANCE, NORDIC REG. Gerrards Cross, UK for the future treatment of more common neu- transfer RNAs (tRNAs), which shuttle amino [email protected] Tel: (44) 1753-892-791 rologic disorders. “What we found particularly acids to cellular subunits called ribosomes for as- striking, when considering the two studies to- sembly into proteins. Mutations affecting mole- ITALY Genoa, Italy gether, is that this is not a condition that we cules involved in producing tRNAs have been im- [email protected] Tel: (39) 10-570-4948 would have been able to separate from other plicated in human neurological disorders, such as JAPAN Tokyo, Japan similar disorders based purely on patient symp- pontocerebellar hypoplasia (PCH), a currently in- [email protected] Tel: (81) 3-5691-3335 toms or clinical features,” said Joseph G. Glee- curable neurodegenerative disease affecting chil- CHINA Shenzen, Guangdong, China son, MD, Howard Hughes Medical Institute in- dren. Although CLP1 mutations have been linked [email protected] Tel: (86) 755-8375-3877 vestigator, professor in the UC San Diego depart- to neuronal death and motor defects in mice, the ALL OTHER COUNTRIES Contact USA Office ments of neurosciences and pediatrics and at role of CLP1 in human disease was not known [email protected] Tel: (1) 954-893-0003 Rady Children’s Hospital-San Diego, a research until now. SUBSCRIPTION INFORMATION affiliate of UC San Diego. “Once we had the These scientists performed DNA sequencing gene spotted in these total of seven families, on children with neurologic difficulties. Seven Bio Research International is published six times a year and circuIated worldwide (outside the USA and Canada) then we could see the common features. It is out of the more than 4,000 families studied without charge and by written request, to qualified re- the opposite way that doctors have defined dis- shared an identical CLP1 mutation, which was searchers, scientists, administrators in research and eases, but represents a transformation in the associated with seizures, motor defects, speech industrial laboratories connected with life sciences, biotechnology, genetics, or medical investigation; and way that medicine is practiced.” impairments, brain atrophy, and neuronal death. others allied to these fields. Each child assessed was affected by undiag- Dr. Bass, from the AMC, noted that the neuro- To all others: Paid Subscription is available for an annual nosed neurological problems. All of the children logical condition represents a new form of PCH. subscription charge of USD 100. Single copy price is USD 20. Mail your paid subscription order accompanied with were discovered to carry a mutation in the CLP1 “Identification of yet another genetic cause for payment to Globetech Media, P.O.Box 802214, Miami, FL gene and displayed the same symptoms, such as this neurodegenerative disorder will allow for 33280-2214. brain malformations, intellectual disabilities, better genetic testing and counseling to families For change of address or questions on your subscrip- seizures and sensory and motor defects. A similar with an affected child,” he said. tion, write to: Bio Research lnternational, Circulation Servic- es at above address, or visit: www.LinkXpress.com pattern emerged in both studies, one led by Glee- In a published paper in 2013, Dr. Gleeson and son, with Murat Gunel, MD, of the Yale Univer- colleagues identified a different gene mutation for ISSN 1939-4470 sity School of Medicine and Frank Baas, PhD, of a particularly severe form of PCH, and reported Vol.19 No.4. Published, under license, by Globe tech Media LLC. early evidence that a nutritional supplement Copyright © 2014. All rights reserved. Reproduction in any form is the Academic Medical Center in the Nether- forbidden without express permission. Opinions expressed are lands, and the other by Josef Penninger and Javier might one day be able to prevent or reverse the solely those of the authors, and do not represent an endorsement, Martinez of the Austrian Academy of Sciences, condition. or lack thereof, by the Publisher of any products or services.

collaborated with James R. Lupski, MD, PhD, of Teknopress Yayıncılık ve Ticaret Ltd. S¸ti. adına the Baylor College of Medicine. Image: Brain MRI slide. A newly identified genetic ˙Imtiyaz Sahibi: M. Geren • Yazı is¸leri Müdürü: Ersin Köklü disorder associated with degeneration of the central Müs¸ir Dervis¸ ˙Ibrahim Sok. 5/4, Esentepe, 34394 S¸is¸li, ˙Istanbul, Türkiye “Knowing fundamental pathways that regu- and peripheral nervous systems in humans, along Faks: (212) 216-6997 • P. K. 1, AVPIM, 34001 ˙Istanbul late the degeneration of neurons should allow us Baskı: Promat Web Ofset Tesisi • Sanayi Mahallesi 1673. Sokak with the genetic cause, has been discovered by re- No: 34 • 34510 Esenyurt, B. Çekmece • ˙Istanbul, Türkiye to define new pathways that, when modulated, searchers (Photo courtesy of Fotolia). Yerel süreli yayındır, iki ayda bir yayınlanır, ücretsiz dag˘ıtılır.

Bio Research International July-August/2014 4 for latest news updates visit www.BiotechDaily.com Bio Research International Nanoparticle Created For Cancer Therapy cont’d from cover low toxicity to healthy cells. Fur- Advances Via Applied Nanotechnology, was test- thermore, Cu-Cy’s intense photo- ing a copper-cysteamine (Cu-Cy) complex created luminescence and X-ray lumines- in his lab when he discovered mysterious decreas- cence can be employed for cell im- es in its luminescence, or light emitting power, aging, according to the scientists. over a time-lapse exposure to X-rays. Researching Details of the crystal structure and further, he discovered that the nanoparticles, optical characteristics of the new called Cu-Cy, were losing energy as they emitted complex are slated for publication singlet oxygen – a toxic byproduct used to dam- in the Journal of Materials Chem- age cancer cells in photodynamic therapy. istry. Prof. Chen reported that ad- Because Prof. Chen also is leading federally ditional research would include re- funded cancer research, he knew he had found ducing the size of the Cu-Cy something unique. Testing revealed that the Cu- nanoparticle to make it more easi- Cy nanoparticles, combined with X-ray exposure, ly absorbed in the tumor tissue. significantly slowed tumor growth in lab studies. “For cancer, there is still no good solution yet. Image: The X-ray destruction of human breast cancer “This new idea is simpler and better than previous Hopefully this nanoparticle can provide some pos- cells using Cu-Cy particles. The images show the live cancer cells stained green and the dead cells stained photodynamic therapy methods. You don’t need sibilities,” he said. red (Photo courtesy of Wei Chen / UT Arlington). as many steps. This material alone can do the job,” Prof. Chen said. “It is the most promising thing we have found in these cancer studies and we’ve been looking at this for a long time.” Prof. Chen’s research will be published in the August 2014 edition of the Journal of Biomed- ical Nanotechnology. The article was published online April 2014. The University has also filed a provisional patent application on the new complex. Photodynamic therapy (PDT) harms cancer cells when a photosensitizer introduced into tumor tissue produces toxic singlet oxygen after being exposed to light. In some studies, this light exposure is done through use of visible or near-infrared lasers. Others have found more success by also introducing luminescent nanoparticles into the tumor. Researchers activate the luminescent nanoparticle with near-infrared light or X-rays, which in turn activates the photosensitizer. Both techniques have limitations for treating deep tissue cancers. They are either ineffective or the light source needed to activate them does not penetrate deep enough. Prof. Chen reported that X-ray-inducible Cu-Cy particles surpass current photosensitizers because the X-rays can penetrate deep into tissue. Furthermore, Cu-Cy nanoparticles do not need other photosensitizes to be effective so the treatment is more convenient, efficient and cost-effective. “Dr. Chen’s commitment to his work in cancer-related therapy, as well as his work in the area of homeland security, demonstrates the wide- ranging applications and great value of basic science research,” said Carolyn Cason, vice president for research at UT Arlington. “These advances have the potential to change the way some cancers are treated and make therapy more effective – a benefit that would be boundless.” Prof, Chen’s team assessed the Cu-Cy on human breast and prostate cancer cells in the lab and found it to be an effective treatment when combined with X-ray exposure. In one esperi- ment, for example, a tumor treated with Cu-Cy injection and X-ray exposure stayed virtually the same size over a 13-day period while a tumor without the full treatment grew by three times. Another benefit of the new nanoparticle is a

Bio Research International 5 July-August/2014 LINKXPRESS COM BRI-08-14 105 Bio Research International for latest news updates visit www.BiotechDaily.com Restoring Effectiveness of Older Antibiotics cont’d from cover penicillins, cephalosporins, and carbapenems, through various mechanisms, resulting in increased mortality rates and hospitalization costs. Microbiol- ogists at the University of South Carolina (Colum- bia, SC, USA; www.sc.edu) introduced a class of charged metallopolymers that exhibit synergistic effects against MRSA by efficiently inhibiting activity of beta-lactamase and effectively lysing bacterial cells. The metallopolymer by itself even demonstrated antimicrobial properties, lysing bacterial cells while leaving human red blood cells unaffected. By a variety of measures, the polymer was found to be nontoxic to human cells in laboratory tests. The beta-lactam structure in a molecule is Image: Conjugates of a beta-lactam antibiotic with the team’s metallopolymer had enhanced antimicrobial properties compared with the antibiotic alone. The effect was particularly striking with hospital-associated MR- something that many bacteria are adverse to. It SA (left) (Photo courtesy of the University of South Carolina). greatly hinders their ability to reproduce by cell division, and so chemists have for years spent time tams studied in detail was enhanced by the poly- Chuanbing Tang, PhD, the lead author of the making molecules that all contain the beta-lactam mer. They prepared a cobaltocenium metallopoly- study said, “Instead of developing new antibiotics, structural motif. One of the most effective bacter- mer that greatly slowed the destructiveness of be- here we ask the question, can we recycle the old an- ial defenses is an enzyme called beta-lactamase, ta-lactamase on a model beta-lactam molecule (ni- tibiotics? With traditional antibiotics like penicillin which chews up the beta-lactam structure. Some trocefin). The enhancement was modest against G, amoxicillin, and ampicillin and so on, can we bacteria, such as MRSA, have developed the abil- two strains, but very pronounced with the hospi- give them new life? In the USA every year, around ity to biosynthesize and release beta-lactamase tal-associated strain of MRSA (HA-MRSA). The 100,000 patients die of bacteria-induced infections, when needed. It is a devastating defense because four antibiotics penicillin-G, amoxicillin, ampi- and the problem is increasing because bacteria are it is so general, targeting the common structural cillin, and cefazolin, were protected from beta-lac- building resistance. It’s a really, really big problem, motif in all of the many beta-lactam antibiotics. tamase hydrolysis via the formation of unique ion- not only for individual patients, but also for society.” The interdisciplinary team also showed that pairs between their carboxylate anions and cation- The study was published on March 17, 2014, in the the antimicrobial effectiveness of the four beta-lac- ic cobaltocenium moieties. Journal of the American Chemical Society. Mass Spectrometry Technology Maps Chemicals as They Migrate into Skin cont’d from cover biomolecular engineering professor who heads the applied them to the surface of skin samples and that desorption electrospray ionization-mass spec- Laboratory for Drug Delivery at Georgia Institute of were able to track the compounds’ migration to a trometry (DESI-MS) imaging has many advantages Technology (Atlanta, GA, USA). depth of 1.2 mm. over other approaches that require complicated DESI-MS was developed 10 years ago and in- Such studies of drug migration are required to preparation of skin samples. volves spraying charged solvent droplets at a sur- enlarge the limited selection of transdermal drugs, Moreover, DESI-MS imaging can be performed face. Backsplash droplets containing dissolved mol- according to Prof. Prausnitz. Only approximately under ambient settings, instead of in a vacuum con- ecules are then captured and examined using a 30 agents, such as nicotine, have transdermal ver- dition, as other MS methods require. Furthermore, mass spectrometer. The technology has been used sions. The drugs must be small, lipophilic, and ef- test compounds do not have to be radioactively la- for medical applications such as imaging drugs in fective at a low dose. With this newly adapted tool, beled or tagged with unwieldy dye molecules that tissue samples. however, scientists could more readily study meth- could affect the compounds’ normal migration The Stanford scientists chose a number of small ods to enhance skin permeation, Prof. Prausnitz re- through skin. “That’s why this method is very ap- molecules that change sodium channels in skin ported. “We’re very interested in the pathway – pealing,” said Mark R. Prausnitz, a chemical and cells, including lidocaine and a shellfish toxin. They which part of the skin did the drug go through?”

Benchtop Line Provides Automated Sample Decapping, Recapping and Identification cont’d from cover When sample tracking is not required, the next- This device decodes multiple types of labware in- The LabElite line from Hamilton Storage Tech- generation LabElite DeCapper is available for de- cluding 2D barcoded tubes in all common 12-, 24- nologies (Franklin, MA, USA; www.hamilton-storage. capping and recapping tubes in 48-cryovial or 96- , 48-, 96- and 384-tube racks including honeycomb- com) offers laboratories an easy and efficient way to microtube racks. A new feature can automatically shaped racks, providing complete sample tracking automatically process and track samples while en- move the racks from portrait to landscape formats during processing. In addition, the reader can iden- suring sample integrity. LabElite devices quickly for processing. Additionally, an innovative “secure tify racks that are labeled with a 2D barcode on the process all common labware types, providing a flex- mode” provides sample security by decapping and bottom. The technology uses high-speed decoding ible solution for optimizing workflows. Three mod- recapping only one row at a time, minimizing the algorithms and parallel processing, which provides els are available to meet a user’s application, time a tube is open and eliminating the risk of cross the fastest run times currently available. A 96-tube throughput, and sample tracking needs. contamination. This feature also enables the rows rack runs in less than 3 seconds and a 384-tube The all-in-one LabElite I.D. Capper enables labs to be paused for “point-of-use” pipetting between rack in less than 5 seconds. Optional 1D barcode to combine decapping/recapping and high-speed capping and recapping, which is very useful for reading of the rack label is also available. The I.D. barcode reading within one device without addi- manual workflows. The DeCapper can process all Reader supports all common tubes, including Ma- tional user interaction. The I.D. Capper is specifical- common tubes, including Matrix, FluidX, Greiner trix, FluidX, Greiner Bio-One, Micronic, Nunc, ly designed to reduce sample contamination and as- Bio-One, Micronic, Nunc, and Corning, with inter- Corning, Matrical, WHEATON, ABgene, and sist with sample tracking during end-to-end auto- nal and external thread caps. REMP. mated liquid-handling processing. The I.D. Capper For labs with manual workflows that need an ef- The LabElite I.D. Capper, DeCapper and I.D. includes all the new features and benefits standard ficient, high-speed 2D barcode reader for tube Reader are for research only, not for use in clinical to the other LabElite devices. racks, the LabElite I.D. Reader is an ideal choice. diagnostic procedures.

Bio Research International July-August/2014 6 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International Graphene Could Reshape Neurological Treatment cont’d from cover lished in the May 2014 issue of Neu- Center (Williamsville, NY, USA; www.invisionhealth. rosurgery. com) argue that neurosurgeons could use gra- “While graphene has been shown phene-based metamaterials, which possess unique to be biocompatible, more basic re- optical, thermal, mechanical, electronic, and quan- search is needed to examine the long- tum properties, to encourage the development of term biological effects of graphene im- high-performance, lightweight, and malleable elec- plants and to answer other important tronic devices, ultracapacitors, optical modulators, clinical questions,” concluded study molecular biodevices, organic photovoltaic cells, authors Tobias Mattei, MD, and lithium-ion microbatteries, frequency multipliers, Azeem Rehman, BSc. “Increased quantum dots, and integrated circuits. awareness of the ongoing frontline re- According to the review, these potential break- search on graphene may enable the throughs in graphene biomedical technology over neurosurgical community to properly the next few decades could significantly impact take advantage of the technological several areas of neurosurgery, including neuro-on- applications such a new metamaterial cology, neurointensive care, neuroregeneration may offer.” research, peripheral nerve surgery, functional neu- Graphene is a monolayer atomic-scale honey- ductivity. The high surface area allows bioconju- rosurgery, and spine surgery. The review also pro- comb lattice of carbon atoms which combines the gation with common biomolecules. Andre Geim vides an introduction to the main properties of greatest mechanical strength ever measured in and Kostya Novoselov of the University of Man- graphene and discusses future perspectives of on- any material (natural or artificial) with very light chester (United Kingdom) were awarded the No- going frontline investigations of graphene, with weight and high elasticity. Graphene has unique bel Prize in Physics in 2010 for its development. special emphasis on research fields that are ex- optical and photothermal properties which allow Image: A close-up view of graphene oxide fiber pected to substantially impact experimental and it to release energy in the form of heat in response structure, which may lead to advances in neuro- clinical neurosurgery. The topic review was pub- to light input; it also has very high electrical con- surgery (Photo courtesy of John Hewitt). Transforming Methylated Nucleic Acids into Prostate Tumor Biomarkers igh quality oligonucleoside reagents and de- supplied by Integrated DNA Technologies (IDT) facil- nucleic acids and exosomes – that can be quantified HHtection kits are facilitating research on methy- itated her research team’s study of prostate cancer. by simple, liquid biopsy. Ultimately, they hope to lated DNA and its relation to the molecular mecha- Research in Dr. Perry’s laboratory is directed at use these biomarkers to develop a noninvasive test nisms that drive development of prostate cancer. understanding how changes in DNA methylation of that will distinguish high-risk from lower-risk In the March 31, 2014, online edition of the In- coding and non-coding RNA genes are involved in prostate tumors. tegrated DNA Technologies (Coralville, IA, USA; driving prostate carcinogenesis. The investigators Integrated DNA Technologies is one of the www.idtdna.com) newsletter DECODED, Dr. An- exploit specific epigenetic changes for early, nonin- largest suppliers of custom nucleic acids in the Unit- toinette Perry, senior research fellow at the Insti- vasive detection of aggressive prostate cancer. In ed States, serving academic, government, and com- tute of Molecular Medicine (Dublin, Ireland; the process, they hope to develop predictive epige- mercial researchers in biotechnology, clinical diag- www.tcd.ie/IMM), described how use of materials netic biomarkers – focusing both on circulating free nostics, and pharmaceutical development.

Bio Research International LINKXPRESS COM BRI-08-14 107 7 July-August/2014 to view this issue in interactive digital magazine format visit www.LinkX- Bio Research International to view this issue in interactivefor digital latest magazine news updates format visit visit www.BiotechDaily.com www.LinkXpress.compress.com Aspirin Use for Heart Disease Prevention May Benefit Those with Coronary Artery Calcium Deposits recent study found that taking aspirin to pre- score = zero) were two to four AAvent heart disease benefits individuals with times more likely to be harmed by high coronary artery calcium (CAC) scores but aspirin use than to benefit. can actually cause damage from bleeding in indi- “We estimate that individuals viduals with low levels of coronary artery calci- with significant plaque buildup in um. the arteries of the heart are much An individual’s CAC score is determined by more likely to prevent a heart at- using computerized tomography (CT) to scan the tack with aspirin use than to suffer coronary blood vessels. Calcium deposits show a significant bleed,” said first au- up as bright white spots on the scan. thor Dr. Michael D. Miedema, a Investigators at the Minneapolis Heart Insti- preventative cardiologist at the tute (MN, USA; www.mplsheart.com) monitored Minneapolis Heart Institute. “On 4,229 individuals participating in the Multi-Eth- the opposite end of the spectrum, if nic Study of Atherosclerosis (MESA) at six cen- you do not have any calcified plaque, our estima- a potential for this test to personalize the ap- ters in the USA. Participants had no known CVD tions indicate that use of aspirin would result in proach to prevention and allow a significant num- (cardiovascular disease) or diabetes, were not on more harm than good, even if you have risk fac- ber of patients to avoid preventive medications, aspirin therapy, and were followed for approxi- tors for heart disease such as high cholesterol or but we need further research to verify that rou- mately seven years. a family history of the disease.” tine use of this test is the best option for our pa- Results revealed that participants with elevat- “A CAC score of zero is associated with a very tients.” ed CAC scores (greater than 100) were two to low risk of having a heart attack. That means in- The study was published in the May 6, 2014, four times more likely to benefit from aspirin dividuals with a score of zero may not benefit online edition of the journal Circulation: Cardio- therapy than to be harmed, even if they did not from preventive medications, such as aspirin as vascular Quality and Outcomes. qualify for aspirin use according to current Amer- well as the cholesterol-lowering statin medica- Image: A computed tomography (CT) scan showing ican Heart Association guidelines. Conversely, tions. Approximately 50% of middle-aged men calcium that has built up in the heart (Photo cour- MESA participants with no calcified plaque (CAC and women have a CAC score of zero, so there is tesy of the Minneapolis Heart Institute).

Monoclonal Antibody Blocks B-Cell Receptor and Eases Leukemia Burden in Mouse Model locking the B-cell-activating factor receptor mally high levels of BAFF may contribute to the the antibodies significantly stimulated natural killer BB(BAFF-R) on leukemia cells has been suggested pathogenesis of autoimmune diseases by enhancing cell-mediated killing of different human patient-de- as a new approach for treating an acute, the survival of autoreactive B cells. The protein en- rived ALL cells. Moreover, incubation of such ALL chemotherapy-resistant form of childhood coded by the TNFRSF13C gene is a receptor for cells with these antibodies stimulated phagocytosis by leukemia. BAFF and is a type III transmembrane protein con- macrophages. When this was tested in the immunod- Acute lymphoblastic leukemia (ALL) is charac- taining a single extracellular cysteine-rich domain. eficient transplant model, mice that were treated terized by an excessive amount of white blood cell It is thought that BAFF-R is the principal recep- with the antibody had a significantly decreased precursors (B-cell lymphoblasts) in the blood and tor required for BAFF-mediated mature B-cell sur- leukemia burden in bone marrow and spleen. bone marrow. B-cell lineage ALL (pre-B ALL) ac- vival. Since BAFF-R is expressed on precursor pre-B “We have now demonstrated that BAFF-R is a counts for 80% to 85% of childhood ALL. ALL cells but not on their pre-B normal counter- strong potential therapeutic target for treating BAFF-R is encoded in humans by the TN- parts, selective killing of ALL cells is possible by tar- chemotherapy-resistant leukemia cells, without FRSF13C (tumor necrosis factor receptor superfam- geting this receptor. damaging healthy cells,” said senior author Dr. No- ily member 13C) gene. BAFF enhances B-cell sur- Investigators at the University of Southern Cali- ra Heisterkamp, professor of research, pediatrics, vival in vitro and is a regulator of the peripheral B- fornia (USA; www.usc.edu) tested a novel human- and pathology at the University of Southern Califor- cell population. Overexpression of BAFF in mice re- ized anti–BAFF-R monoclonal antibody in a study nia. “We found that human pre-B ALL cells could sults in mature B-cell hyperplasia and symptoms of carried out on leukemia cell cultures and in an im- be even further reduced when the anti-BAFF-R an- systemic lupus erythematosus (SLE). Also, some munodeficient mouse transplant model. tibody was combined with chemotherapy or anoth- SLE patients have increased levels of BAFF in their They reported in the May 13, 2014, online edition er therapeutic agent. We are looking at a potential serum. Therefore, it has been proposed that abnor- of the journal Molecular Cancer Therapeutics that one, two punch.” Novel Approach Simplifies Complex Sugars on Protein-Based Biotech Medicines team of biotech medicine developers has es- which used a fungal enzyme to shorten the Golgi tent performance of therapeutic proteins and mod- AAtablished a cell-based production method that N-glycosylation pathway in mammalian cells. ulation of biopharmaceutical functions. reduces the complexity of the sugars (glycans) ex- They wrote in the April 20, 2014, online edition Senior author Dr. Nico Callewaert, professor of pressed on protein-based drugs. of the journal Nature Biotechnology that this short- medical biotechnology at Ghent University, said, Heterogeneity in the N-glycans on therapeutic ening resulted in the expression of proteins with “This technology has allowed us to solve an old proteins causes difficulties for protein purification small, sialylated trisaccharide N-glycans and re- biotech problem. Since the 1990s, nearly everyone and process reproducibility and can lead to variable duced complexity compared to native mammalian has been working to make the sugar synthesis in therapeutic efficacy. This heterogeneity arises from cell glycoproteins. GlycoDelete engineering did not biotech production cells as similar to human cells as the multistep process of mammalian complex-type interfere with the functioning of N-glycans in pro- possible. This is a very difficult task, because there N-glycan synthesis. tein folding, and the physiology of cells modified by are so many steps in this synthesis pathway. We Investigators at, Ghent University (Belgium; GlycoDelete was similar to that of wild-type cells. have been able to create a detour in this synthesis www.ugent.be) recently described a novel glyco- This strategy for reducing N-glycan heterogeneity pathway in a fairly simple manner, making the path- engineering strategy that they called GlycoDelete, on mammalian proteins could lead to more consis- way much shorter and simpler.”

Bio Research International July-August/2014 8 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International Melanoma Triggered by Deficit of Retinoid-X-Receptors in Melanocytes ancer researchers have linked the develop- tually help promote it. When there is not CCment of the deadly skin cancer melanoma enough RXR, the melanocytes that exist to help to depressed expression in melanocytes of the shield against cancer ultimately become part of type II nuclear receptors Retinoid-X-Receptor al- the problem. It is routine to have genetic dam- pha (RXRalpha) and Retinoid-X-Receptor beta age from sunlight, because normally those cells (RXRbeta). can be repaired or killed if necessary. It is the Melanoma is the deadliest form of skin can- breakdown of these control processes that result cer. It derives from melanocytes, the melanin- in cancer, and that happens when RXR levels get producing cells of the skin, which give the skin too low. It is quite possible that a new and effec- its tone in addition to protecting it from harmful tive therapy can now be developed, based on in- effects of ultraviolet radiation (UVR). Changes creasing levels of RXR.” in the skin microenvironment, such as signaling from other cell types, can influence melanoma progression. While several key genes in Image: Arup and Gitali Indra are urgently seeking, melanoma development have been identified, and beginning to find, clues to predicting, prevent- the underlying mechanisms are complex; differing and stopping melanoma before it spreads (Photo courtesy of Karl Maasdam / Oregon State ent combinations of mutations can result in University College of Pharmacy). melanoma formation and genetic profiles of tumors can vary greatly among patients. Retinoid X receptors (RXRs) are nuclear receptors that mediate the biological effects of retinoids (vitamin A derivatives) by their in- volvement in retinoic acid-mediated gene activation. These receptors function as transcription factors by binding as homodimers or het- erodimers to specific sequences in the promot- ers of target genes. The protein encoded by this gene is a member of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. Since expression of RXRalpha disappears during melanoma progression in humans, investigators at Oregon State University (Corval- lis, USA; www.oregonstate.edu) developed a tissue-specific gene ablation strategy to characterize the role of these type II nuclear receptors in melanocytes to control UVR-induced skin immune responses and cell survival. They reported in the May 8, 2014, online edition of the journal PLoS Genetics that melanocytes in mice with melanocyte-specific ablation of RXRalpha and RXRbeta attracted fewer IFN-gamma (interferon-gamma) secret- ing immune cells than in wild-type mice following acute UVR exposure, via altered expression of several chemoattractive and chemore- pulsive chemokines/cytokines. Reduced IFN- gamma in the microenvironment altered UVR- induced apoptosis, and due to this, the survival of surrounding dermal fibroblasts was significantly decreased in mice lacking RXRalpha/beta. These results emphasized a novel im- munomodulatory role for melanocytes in controlling survival of neighboring cell types be- sides controlling their own, and identified RXRs as potential targets for therapy against UV induced melanoma. “We believe this is a breakthrough in understanding exactly what leads to cancer formation in melanoma,” said senior author Dr. Arup Indra, associate professor of pharmacology at Oregon State University. “We have found that some of the mechanisms which ordinarily prevent cancer are being switched around and ac-

Bio Research International 9 July-August/2014 LINKXPRESS COM BRI-08-14 109 to view this issue in interactive digital magazine format visit www.LinkX- Bio Research International to view this issue in interactivefor digital latest magazine news updates format visit visit www.BiotechDaily.com www.LinkXpress.compress.com Genomic Studies Reveal Links Between Prostate Cancer and Cardiovascular Disease large-scale statistical evaluation of genomic edition of the International Jour- AAstudies linked to either prostate cancer (PCA) nal of Epidemiology revealed or cardiovascular disease (CVD) risk identified 17 that the strongest association be- genetic loci that link prostate cancer to risk of de- tween PCA and CVD risk was veloping CVD. conditional on LDL and TG. In Investigators at Oslo University (Norway; contrast, the investigators found www.uio.no) and their colleagues at the Universi- only weak enrichment condi- ty of California, San Diego (USA; www.ucsd.edu) tional on HDL or conditional on applied a genetic epidemiology method based on the other traits investigated. conjunction false discovery rate (FDR) that com- Conjunction FDR identified alto- bined summary statistics from different genome- gether 17 loci; 10 loci were as- wide association studies (GWAS), and allowed sociated with PCA and LDL, identification of genetic overlap between two phe- three loci were associated with notypes. FDR is a statistical method used in mul- PCA and TG and additionally tiple hypotheses testing to correct for multiple four loci were associated with comparisons. In a list of findings, FDR procedures PCA, LDL, and TG jointly. are designed to control the expected proportion of “It is fair to say that risk rela- incorrectly rejected null hypotheses. tionships of various sorts have The investigators evaluated summary statistics been proposed between prostate from large, multicenter GWA studies of PCA (n = cancer and cardiovascular disease, although not tion with LDL cholesterol and triglycerides versus 50,000) and CVD risk factors (n = 200,000). CVD comorbidity per se,” said contributing author Dr. the other traits at a genetic level was novel and risk factors included triglycerides (TG), low-densi- Ian G. Mills, researcher in the prostate cancer unexpected.” ty lipoprotein (LDL) and high-density lipoprotein group at the University of Oslo. “There is a lack of (HDL) cholesterol, systolic blood pressure, body consistency across cohorts, however, in size and Image: Micrograph of normal prostatic glands and those with prostate adenocarcinoma (upper right mass index, waist-hip ratio, and type II diabetes. direction of effects, depending on cardiovascular portion of image) (Photo courtesy of Wikimedia Results published in the April 30, 2014, online risk factor considered. The significant risk associa- Commons). Barth Syndrome Stem Cells Reveal Details of a Rare Heart Defect kin cells taken from Barth syndrome patients from two Barth syndrome patients. The skin cells lished in the May 11, 2014, online edition of the SSwere used to generate stem cells that differenti- were induced to become stem cells carrying the pa- journal Nature Medicine showed that inducing ated into defective heart tissue in culture. tients’ TAZ mutations. The stem cells were cultured TAZ mutation in normal cardiomyocytes weakened Barth syndrome (type II 3-Methylglutaconic on chips lined with human extracellular matrix contractions while addition of normal TAZ to the aciduria) is caused by mutation of the tafazzin gene. (ECM) proteins that mimicked their natural envi- Barth syndrome cardiomyocytes corrected the con- Tafazzin is responsible for remodeling of a phospho- ronment. Under these conditions the stem cells ma- tractile defect. lipid cardiolipin (CL), the signature lipid of the mi- tured into a conglomerate of cardiomyocytes that “The TAZ mutation makes Barth syndrome cells tochondrial inner membrane. As a result, Barth syn- mimicked heart tissue. Due to the presence of the produce an excess amount of reactive oxygen drome patients exhibit defects in CL metabolism, TAZ mutations the heart tissue demonstrated very species, or ROS – a normal byproduct of cellular including aberrant CL fatty acyl composition, accu- weak contractions, similar to a diseased human metabolism released by mitochondria – which had mulation of monolysocardiolipin (MLCL), and re- heart. not been recognized as an important part of this dis- duced total CL levels. About 120 cases of Barth syn- The investigators used this novel model system ease,” said senior author Dr. William Pu, associate drome, which is found exclusively in males, have to define metabolic, structural, and functional ab- professor of cardiology at Harvard University. “We been documented to date, but the syndrome is be- normalities associated with TAZ mutation. They showed that, at least in the laboratory, if you lieved to be severely under-diagnosed and has been found that excess levels of reactive oxygen species quench the excessive ROS production then you can estimated to occur in one out of approximately (ROS) mechanistically linked TAZ mutation to im- restore contractile function. “Now, whether that 300,000 births. paired cardiomyocyte function. In addition, they can be achieved in an animal model or a patient is Investigators at Harvard University (Cambridge, used a gene therapy technique to provide the nor- a different story, but if that could be done, it would MA, USA; www.harvard.edu) obtained skin cells mal TAZ protein to the diseased tissue. Results pub- suggest a new therapeutic angle.”

A Pair of Gene Splice Isoforms Has Opposite Effects on Cancer Development wo distinct splice isoforms of the MAP kinase Jerusalem (Israel; www.huji.ac.il) reported in the These results suggested that Mnk2 alternative TTinteracting serine/threonine kinase 2 April 10, 2014, online edition of the journal Cell splicing served as a switch in several cancers to (MKNK2) gene have dramatically different roles in Reports that the Mnk2a isoform was a tumor sup- downregulate a tumor suppressor isoform (Mnk2a) cancer development and growth. pressor that was downregulated in human cancers. that activates the p38-MAPK stress pathway and to It is known that the protein products of MKNK2 This isoform interacted with, phosphorylated, and induce an isoform (Mnk2b) that does not activate phosphorylate the eukaryotic initiation factor 4E activated p38-MAPK, leading to activation of its tar- this pathway and is pro-oncogenic. (eIF4E), thus playing important roles in the initia- get genes and to p38alpha-mediated cell death. “The mechanism we discovered explains how tion of mRNA translation, oncogenic transforma- Thus, Mnk2a downregulation by alternative splic- cancer cells eliminate the anticancer form of Mnk2 tion, and malignant cell proliferation. However, it ing was a tumor suppressor mechanism that was without changing their DNA, and how they be- has come to light that MKNK2 is alternatively lost in some breast, lung, and colon tumors. come resistant to anticancer treatments – a prob- spliced with the two splicing isoforms having differ- On the other hand, the Mnk2b isoform was lem which exists for almost every cancer treatment ent last exons: Mnk2a, which contains a MAPK- found to be pro-oncogenic and did not activate p38- today,” said senior author Dr. Rotem Karni, senior binding domain, and Mnk2b, which lacks it. MAPK, while still enhancing eIF4E phosphoryla- lecturer of biochemistry and molecular biology at Investigators at the Hebrew University of tion. the Hebrew University of Jerusalem.

Bio Research International July-August/2014 10 for latest news updates visit www.BiotechDaily.com Bio Research International Loss of Ron Signaling Linked to Development of Inflammatory Bowel Disease ancer researchers have found that decreased molecular signaling by the CCRon receptor tyrosine kinase (macrophage-stimulating protein receptor) is linked to the development of inflammatory bowel disease (IBD), a group of chronic inflammatory disorders of the intestine that result in painful and debil- itating complications. The Ron receptor tyrosine kinase, a member of the MET proto-oncogene family, is a pathogenic factor implicated in tumor malignancy. Specifically, aberrations in Ron signaling result in increased cancer cell growth, survival, invasion, angiogenesis, and drug resistance. Biochemical events such as ligand binding, receptor overexpression, generation of structure-defected variants, and point mutations in the kinase domain contribute to Ron signaling activation. Investigators at the University of Cincinnati (Ohio, USA; www.uc.edu) have now found that decreased Ron signaling is linked to the development of IBD. This data was obtained from experiments conducted with a line of mice that had been genetically engineered to lack the tyrosine kinase signaling domain of Ron (TK-/- mice). These animals and wild-type controls were utilized as a well-characterized model of chronic colitis induced by cyclic exposure to dextran sulfate sodium. Results reported in the April 17, 2014, online edition of the American Journal of Physiology- Gastrointestinal and Liver Physiology revealed that TK-/- mice were more susceptible to injury as PREMIER MULTIMEDIA PLATFORM judged by increased mortality compared to control mice and developed more severe colitis. In addi- SERVING THE WORLD'S tion, loss of Ron led to significantly reduced body LIFE SCIENCE RESEARCHERS weights and more aggressive clinical histopatholo- gies. Ron loss also resulted in a dramatic reduction in colonic epithelial cell proliferation and in- Anytime, Anywhere, On the Go... creased proinflammatory cytokine production, which was associated with alterations in impor- PRINT MAGAZINE tant signaling pathways known to regulate IBD. “Genome-wide linkage studies have identified the Ron receptor tyrosine kinase and its hepato- cyte growth factor-like protein (HGFL) as genes highly associated with IBD,” said senior author Dr. Susan Waltz, professor in of cancer biology at the University of Cincinnati. “However, only scant information exists on the role of Ron or HGFL in IBD. Based on the linkage of Ron to IBD, INTERACTIVE we examined the biological role of Ron in colitis.” DIGITAL EDITION “We found that genetic loss of Ron led to aggressive inflammation and damage to the colon of WEB PORTAL models with IBD,” said Dr. Waltz. “In addition, there are a number of small changes called single nucleotide polymorphisms (SNP) in humans which map to both the Ron and HGFL gene and have been identified to strongly associate IBD disease in humans. Our studies suggest that these SNPs may reduce the function of Ron and HGFL leading to chronic intestinal inflammation and damage. With the knowledge that we have gained in studying these proteins in cancer biology, we hope this information may be translated to help patients with Crohn’s disease and ulcerative colitis. Further studies on the Ron signaling pathway are needed and could reveal an important new target for these conditions.”

Image: Researcher Susan Waltz, PhD, and scientists in her lab have done what is believed to be the first direct genetic study to document the important function for the Ron receptor, a cell surface protein often found in certain cancers, and its genetic growth factor, responsible for stimulating cell growth, in the development and progression of IBD (Photo biotechdaily.com courtesy of Cincinnati Cancer Center / University of Cincinnati Cancer Institute).

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MICRO BIOREACTOR HPLC RADIOACTIVITY DETECTOR MICRO-VOLUME PROBES Applikon Biotechnology Berthold Technologies Bibby Scientific The micro-Matrix offers an integrated, easy-to-use The FlowStar LB 513 features a user-friendly The micro-volume probes from Jenway are de- technology platform for the rapid handling and touch screen, an automatic measuring cell identi- signed for the accurate measurement of solutions growth of large numbers of microbial strains, fication system, and two integrated bipolar analog in volumes as low as 150 µl. The probes are suit- clone libraries, mutant banks, and cells. The sys- inputs. The GLP/GMP functionality has been able for test tubes/small vessels and are available tem features 24 independent bioreactors in a added so users can continuously supervise all rel- in two variants, a 4-mm probe with a 120-mm cost-effective microtiter plate footprint. evant parameters simply by pushing a button. reach, and a 6-mm probe with a 180-mm reach.

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Next-Generation Bio-Safety Cabinet Provides Flexible Animal Handling Solutions iotech and other life science laboratories that filter loading without a significant reduction in air BBwork with animals will benefit from a new delivery. The technician is protected from air- line of next-generation biological safety cabinets. borne contaminants by an aerodynamic air foil The new LabGard ES NU-677 Animal Class II, that returns air into the front grill. The advanced Type A2 Animal Handling Biological Safety Cabi- motor system reduces operating costs by 40%, as net and Cage Changing Station is manufactured it generates less heat and reduces stress while op- and marketed by NuAire (Plymouth, MN, USA; erating at lower decibel levels. www.nuaire.com), an industry leader in laborato- The NU-677 has been certified by the Nation- ry equipment manufacturing for more than 40 al Sanitation Foundation (Ann Arbor, MI, USA; years. www.nsf.org) according to ANSI 49. The Nation- The NU-677 is remarkably flexible, being both al Sanitation Foundation was founded in 1944 mobile and height adjustable. These features help with the mission to protect and improve global to reduce strains that develop from repeated human health. As an independent, accredited or- design, construction, and performance of bio-safe- movements in the arm, neck, and shoulder of lab- ganization, it develops standards and tests and ty cabinets to NSF/ANSI Standard 49 and runs oratory workers. A pre-filter built into the back certifies products and systems. In addition, it pro- the Bio-safety Cabinet Field Certifier Accredita- wall of the cabinet extends the working life of the vides auditing, education, and risk management tion Program. HEPA filters by trapping animal hair and dander. solutions for public health and the environment. Image: The LabGard model NU-677 animal handling Thus, the cabinet can handle a 300% increase in The National Sanitation Foundation certifies the biological safety cabinet (Photo courtesy of NuAire).

AFM-Enabled Scanning Electrochemical Microscopy Launched new atomic force microscopy (AFM)-enabled ies of corrosion processes. special sample plates designed specifically for EC ap- AAScanning Electrochemical Microscopy (SECM) At the technological core of Agilent’s SECM plications, as well as a new dual-chamber glove box mode includes an integrated technology package mode is the novel EC SmartCart, an easy-to-handle that fits within an acoustic isolation chamber, en- that enables scientists to perform scanning electro- cartridge that combines a nanoelectrode with a pre- hance experimental control. In addition, a built-in chemical microscopy on conductive and insulating mounted AFM tip. EC SmartCart probes come potentiostat affords scientists a series of different samples. pretested and ready-to-scan for Agilent atomic force sensitivity settings covering four orders of magni- The system uses an Agilent (Santa Clara, CA, microscopes. A customized nose cone for the scan- tude of currents. Full-featured Agilent PicoView USA; www.agilent.com) atomic force microscope, ner accepts the cartridge. software further extends experimental flexibility which can be used in a timesaving manner, with Produced via microfabrication techniques, the bi- and control plus functions for Chronoamperometry nanoscale resolution. Agilent designed the SECM functional probes ensure a constant and controlled and Differential Pulse Voltammetry experiments, mode to deliver both good performance and ease of distance between the tip-integrated electrode and among others. Agilent’s new SECM mode can im- use. Hours of setup time are eliminated, so data can the sample surface, significantly improving perform- prove the vision of electrochemistry science at the be collected immediately. ance. Agilent’s EC SmartCart probes enable high- nanoscale. The new SECM mode provides great utility for a resolution topographical imaging while simultane- An environmental chamber and special sample broad range of applications. These include investiga- ously mapping electrochemical information via the plates designed specifically for EC applications, as tions of homogeneous and heterogeneous electron AFM probe-integrated electrode. well as a new dual-chamber glove box that fits with- transfer reactions, imaging of biologically active The probes provide scientists with inherently in an acoustic isolation chamber, enhance experi- processes, surface modification, analysis of thin films synchronized structure-activity information. SECM mental control. In addition, a built-in potentiostat af- (e.g., pinhole detection, conformality), screening of mode also offers scientists industry-leading in situ re- fords scientists a series of different sensitivity set- catalytic material (e.g., fuel cell catalysts), and stud- search capabilities. An environmental chamber and tings covering four orders of magnitude of currents.

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MICROPLATES MICROPLATE SPECTROPHOTOMETER DIGITAL MICROSCOPE Biotage BioTek Instruments Carl Zeiss Microscopy The ISOLUTE SLE+ 48-well microplates are de- The Epoch 2 combines touch screen and onboard The ZEISS Smartzoom 5 features an optical en- signed to enable extraction of larger sample vol- data analysis software for efficient operation and gine that combines three functions in a single umes (1 mL total load volume). The plates are ide- reporting of absorbance-based detection work- component: zoom, overview camera, and coaxial al for extraction of small molecule drugs, metabo- flows. The system offers a spectral range of 200- illumination. The system is ideal for QC/QA appli- lites, and endogenous biomarkers from biological 999 nm, selectable in 1 nm increments, for single-, cations, delivering repeatable results, enhanced fluid samples prior to LC-MS/MS and GC-MS. dual-, and multi-wavelength measurements. images, and easy documentation.

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Electronic Pipetting System Boasts Adjustable Tip Distances recently introduced electronic pipetting sys- spacing allows users to transfer multiple samples AAtem – now available for biotech and life sci- between different labware formats using one ence researchers – boasts the ability to adjust the pipette, resulting in fewer repetitions and 90% distance between tips while maintaining precise less time compared to single channel manual sample volumes on every channel. pipettes. The Thermo Fisher Scientific (Milford, MA, “Scientists working in liquid handling and sam- USA; www.thermofisher.com) E1-ClipTip elec- ple preparation need pipettes they can trust,” said tronic pipettes combine the security of the propri- Raymond Mercier, business director, liquid trans- etary “Cliptip” tip locking mechanism with the fer at Thermo Fisher Scientific. “The Thermo Sci- freedom of adjustable tip spacing. entific E1-ClipTip electronic pipette’s interlocking Cliptip enables secure tip attachment with low technology provides outstanding sample security tip attachment and ejection forces. The system and makes pipetting more efficient with the abili- guarantees an airtight seal on every channel, ty to transfer samples quickly between different which ensures consistent and accurate liquid labware formats using the same pipette through- Image: The E1 ClipTip multichannel pipette (Photo transfer for higher quality results. Adjustable tip out the protocol.” courtesy of Thermo Fisher Scientific). Brain Buffer System Overcomes Molecular Disturbances in Circadian Clock ew evidence has been found for neuronal net- 60%) or strongly (90%). To the best of their knowl- not sufficient to drive outputs of peripheral oscilla- NNwork communication that helps create a be- edge, this is the first time CTOs have been partially tors, while circadian rhythms in locomotor activity havioral buffer in the brain to overcome certain dis- damped in a living organism and their role assessed were resistant to these partial reductions. This re- turbances in the molecular level circadian clock comprehensively. silience of the brain oscillator was found to depend rhythms. The researchers postulated that in the brain, on communication among circadian neurons in the Circadian clocks time the sleep/wake cycles as communication among the circadian neuronal brain. Indeed, the capacity of the brain oscillator to well as many other physiological and cellular path- groups can compensate for the dampened CTOs. overcome the low amplitude CTOs depends on the ways to daily 24 hour rhythms. In Drosophila, This is not surprising, as results from studies on lo- action of the neuropeptide PDF and on the pdf-ex- CLOCK (CLK) and CYCLE (CYC) proteins initiate comotor activity patterns in mammals with core pressing cells having equal or higher amplitude of the circadian system by promoting rhythmic tran- clock protein mutations are among the same lines. CTOs than the rest of the circadian neuronal scription of hundreds of genes. Abolishment of cir- However, in mammals the molecular machinery groups in the brain. cadian transcriptional oscillations (CTOs) has been that drives circadian rhythms in the central versus These findings support the idea of network shown to abolish circadian function. However, pre- the peripheral oscillators differs, whereas this does buffering mechanisms that allows the brain to drive vious studies used manipulations in which the abol- not seem to be the case in flies. Yet, in this study, robust behavioral circadian rhythms even with low ishment of the CTOs was very dramatic and in- the partial decrease in the amplitude of CTOs led to amplitude molecular oscillations. Therefore, in ad- volved strong up- or down-regulation of circadian impaired function of circadian outputs in peripher- dition to revealing the importance of high ampli- genes. al functions but did not significantly affect circadian tude CTOs for cell-autonomous circadian timekeep- In this study, a research team led by Sebastian locomotor behavior. This suggests that the clock in ing, this work demonstrates that the brain’s circadi- Kadener, assistant professor at the Hebrew Univer- the brain has a specific compensatory mechanism. an neuronal network has an essential system that sity of Jerusalem (Israel; www.huji.ac.il), used an Moreover, flies with reduced CTOs that also had protects against disturbances in circadian transcrip- innovative genetic approach that enabled them to impaired circadian neuronal communication dis- tion in the brain. generate Drosophila melanogaster fruit flies in played aberrant circadian behavior rhythms. The study, by Weiss R. et al., was described in which the amplitude of CLK-driven CTOs was re- The partially reduced CTOs led to low ampli- the journal PLOS Genetics, published April 3, duced in a controlled way, either partially (approx. tude circadian protein oscillations (CPOs) that were 2014.

Bio Research International July-August/2014 14 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International Nanodelivery System Securely Targets Cancer Cells cientists have devised a tunable virus that works “these viruses unlock, bind to the cells and deliver SSsimilar to a safe deposit box. It takes two keys to payloads that will either kill the cells for cancer ther- open it and release its therapeutic payload. apy or deliver genes that can fix them for other dis- The Rice University (Houston, TX, USA; www. ease applications.” rice.edu) laboratory of bioengineer Dr. Junghae Suh Dr. Suh’s lab genetically inserts peptides into the has developed an adeno-associated virus (AAV) that self-assembling AAVs to lock the capsids, the hard unlocks only in the presence of two selected pro- shells that protect genes positioned within. The tar- teases, enzymes that cut up other proteins for dis- get proteases spot the peptides “and chew off the posal. Because specific proteases are elevated at tu- locks,” effectively unlocking the virus and allowing mor sites, the viruses can be designed to target and it to attach to the diseased cells. “If we were just destroy the cancer cells. looking for one protease, it might be at the cancer The research was published online May 5, 2014, site, but it could also be somewhere else in your in the American Chemical Society (ACS) journal body where you have inflammation. This could lead ACS Nano. AAVs are comparatively benign and to undesirable side effects,” she said. “By requiring Alzheimer’s diseases, and heart diseases, including have been intensely studied as delivery vehicles for two different proteases – let’s say protease A and myocardial infarction and congestive heart failure. gene therapies. Researchers frequently try to target protease B – to open the locked virus, we may The eventual outcome of this technology is to AAVs to cellular receptors that may be somewhat achieve higher delivery specificity since the chance design viruses that can carry out a combination of overexpressed on diseased cells. of having both proteases elevated at a site becomes steps for targeting. “To increase the specificity of The Rice lab takes a different tactic. “We were smaller.” virus unlocking, you can imagine creating viruses looking for other types of biomarkers beyond cellu- Molecular-imaging techniques in the future will that require many more keys to open,” Dr. Suh stat- lar receptors present at disease sites,” Dr. Suh said. be used to detect both the identity and concentra- ed. “For example, you may need both proteases A “In breast cancer, for example, it’s known the tumor tion of elevated proteases. “With that information, and B as well as a cellular receptor to unlock the cells oversecrete extracellular proteases, but per- we would be able to pick a virus device from our virus. The work reported here is a good first step to- haps more important are the infiltrating immune panel of engineered variants that has the right prop- ward this goal.” cells that migrate into the tumor microenvironment erties to target that disease site. That’s where we Image: An adeno-associated virus capsid (blue) and start dumping out a whole bunch of proteases want to go,” Dr. Suh said. modified by peptides (red) inserted to lock the virus as well. So that’s what we’re going after to do target- Dr. Suh reported that elevated proteases are is the result of research into a new way to target can- ed delivery. Our basic idea is to create viruses that, found around many diseased tissues. She suggested cerous and other diseased cells. The peptides are in the locked configuration, can’t do anything. these protease-activatable viruses may be useful for keyed to proteases overexpressed at the site of diseased tissues; they unlock the capsid and allow it to They’re inert,” she said. When programmed AAVs the treatment of not only cancers but also neurolog- deliver its therapeutic cargo (Photo courtesy of Jung- encounter the right protease keys at sites of disease, ic diseases, such as stroke, Parkinson’s and hae Suh / Rice University).

Molecules Engineered to Fight Alzheimer’s And Other Neurodegenerative Disorders esearchers have engineered a set ized by misfolded proteins. GAIM has RRof molecules with the potential the potential to provide a more robust to treat most neurodegenerative dis- response than previous therapies be- eases that are characterized by mis- cause it enables the simultaneous tar- folded proteins, such as Alzheimer’s, geting of multiple pathologies within a Parkinson’s, and Huntington’s dis- single disease,” said Dr. Richard Fisher, eases. These molecules are based on chief scientific officer at NeuroPhage. what NeuroPhage Pharmaceuticals, The findings of this technology were Inc. (Cambridge, MA, USA; www. published online April 22, 2014, in neurophage.com), the developer of the Journal of Molecular Biology. the technology, calls a general amy- Researchers used a range of tech- loid interaction motif (GAIM), which niques, including X-ray fiber diffrac- recognizes a characteristic that is tion and nuclear magnetic reso- typical to many toxic, misfolded pro- nance spectroscopy (NMRS), to teins, not only one type of misfolded demonstrate the activities of GAIM. protein. This approach provides a They found that GAIM effectively range of therapeutic targets, so that a binds to multiple types of misfolded number of pathologies, such as amy- proteins during their formation in loid beta plaques, tau tangles and al- such a way that prevents new toxic pha-synuclein Lewy bodies, can all protein aggregates from forming. be tackled simultaneously with a sin- Furthermore, upon incubating gle drug candidate. GAIM with various misfolded pro- Moreover, GAIM molecules have teins, the researchers observed that been shown to not only prevent the GAIM disrupted these assemblies of formation of new toxic protein aggre- misfolded proteins by causing a con- gates but can also dissipate existing formational alteration in their struc- aggregates in the form of both solu- tures. This structural change could ble oligomers and insoluble fibers, enable the body’s natural disposal such as plaques and tangles. processes to recognize and clear the “The research published […] de- misfolded proteins, which in princi- scribes GAIM, NeuroPhage’s unique ple, would enable the brain to re- approach to treat diseases character- turn to a more normal state.

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LIQUID HANDLING PLATFORM PURIFICATION PROTOCOL SERUM REPLACEMENT CyBio EMD Millipore Essential Pharmaceuticals The CyBi-FeliX flexible system is designed for sin- The new recombinant protein purification protocol The Cell-Ess is a replacement for the FBS com- gle to multichannel pipetting on a small footprint of combines lysis and protein purification in one monly used in cell culture. It is chemically defined 650 mm x 450 mm. The deck offers 12 positions step. The condensed workflow reduces process- and animal component-free, enables researchers for microplates, tube racks, reservoirs, and tips, ing time by 75% compared to traditional methods, to eliminate FBS use in basic research and bio- with optional accessories available such as tip while delivering high purity, greater consistency, production of proteins or cells, and delivers critical wash station and microplate heating/cooling. and more reproducible yields. components that are needed for cell growth.

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RNA Interference Mechanism May Be Used to Treat Cancer NA carried by new nanoparticles can silence strands of RNA called siRNA attach to the RRgenes in many organs, and researchers be- messenger RNA that carries this genetic in- lieve that it could be utilized to treat cancer. formation, preventing it from reaching the RNA interference (RNAi), a technique that can ribosome. inactivate specific genes inside living cells, holds Drs. Anderson and Langer have earlier great potential for treating many disorders caused developed nanoparticles, now in clinical by malfunctioning genes. However, it has been dif- development, that can deliver siRNA to liv- ficult for scientists to find safe and effective ways to er cells called hepatocytes by coating the deliver gene-blocking RNA to the correct targets. nucleic acids in fatty compounds called Up to now, researchers have received the best lipidoids. Hepatocytes clutch onto these results with RNAi targeted to diseases of the liver, particles because they resemble the fatty partly because it is a normal endpoint for nanopar- droplets that circulate in the blood after a ticles. But now, in a study appearing in the May high-fat meal is consumed. “The liver is a 11, 2014, issue of the journal Nature Nanotech- natural destination for nanoparticles,” Dr. nology, a Massachusetts Institute of Technology Anderson stated. (MIT; Cambridge, MA, USA; www.mit.edu)-led Scientists have had some success deliver- team reported achieving the most effective RNAi ing RNA to nonliver organs, but the MIT sci- gene silencing to date in nonliver tissues. entists wanted to formulate an approach that could To demonstrate the potential for treating lung Using nanoparticles designed and screened for achieve RNAi with lower doses of RNA, which disease, the researchers used the nanoparticles to endothelial delivery of short strands of RNA called could make the treatment more effective and safer. block two genes that have been implicated in lung siRNA, the researchers were able to target RNAi The new MIT particles consist of three or more cancer – vascular endothelial growth factor to endothelial cells, which form the linings of concentric spheres made of short chains of a (VEGF) receptor 1 and Dll4, which encourage the most organs. This raises the possibility of using chemically modified polymer. RNA is packaged growth of blood vessels that feed tumors. By RNAi to treat many types of disease, including within each sphere and released once the particles blocking these in lung endothelial cells, the re- cancer and cardiovascular disease, according to enter a target cell. A major aspect of the MIT sys- searchers were able to slow lung tumor growth in the researchers. tem is that the scientists were able to create a “li- mice and also reduce the spread of metastatic tu- “There’s been a growing amount of excitement brary” of many different substances and rapidly mors. about delivery to the liver in particular, but in or- evaluate their potential as delivery agents. They Dr. Masanori Aikawa, an associate professor of der to achieve the broad potential of RNAi thera- evaluated about 2,400 variants of their particles in medicine at Harvard Medical School (Boston, peutics, it’s important that we be able to reach cervical cancer cells by measuring whether they MA, USA; http://hms.harvard.edu), described other parts of the body as well,” remarked Dr. could turn off a gene coding for a fluorescent pro- the new technology as “a monumental contribu- Daniel Anderson, an associate professor of chemi- tein that had been added to the cells. They then tion” that should help researchers develop new cal engineering, a member of MIT’s Koch Institute tested the most promising of those in endothelial treatments and learn more about diseases of en- for Integrative Cancer Research and Institute for cells to see if they could interfere with a gene dothelial tissue such as atherosclerosis and diabet- Medical Engineering and Science, and one of the called TIE2, which is expressed almost exclusive- ic retinopathy, which can cause blindness. study’s senior authors. The article’s other senior ly in endothelial cells. The researchers next plan to explore addition- author is Dr. Robert Langer, a professor at MIT With the best-performing particles, the real potential targets in hopes that these particles and a member of the Koch Institute. searchers reduced gene expression by more than could eventually be deployed to treat cancer, ath- Discovered in 1998, RNAi is a naturally occur- 50%, for a dose of only 0.20 mg/kg of solution – erosclerosis, and other diseases. ring process that allows cells to control their ge- about one-hundredth of the amount required with netic expression. Genetic data are typically car- existing endothelial RNAi delivery vehicles. They Image: Lipid nanoparticles (carrying siRNA) are shown as they are transported inside cells using en- ried from DNA in the nucleus to ribosomes, cellu- also showed that they could block up to five genes docytic vesicles (Photo courtesy of Daria Alakhova lar structures where proteins are produced. Short at once by delivering different RNA sequences. and Gaurav Sahay).

Bio Research International July-August/2014 16 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International Possible Target for Gene Therapy May Correct Cardiac Hypertrophy deficit in the expression of the ings of the National Academy of AAprotein Erbin (ErbB2 interact- Sciences of the United States of ing protein) has been linked to the America (PNAS) that there was development of cardiac hypertrophy down-regulation of Erbin expression and heart failure. in biopsies derived from human fail- The gene that encodes the Erbin ing hearts. protein is a member of the leucine- In mouse models cardiac hyper- rich repeat and PDZ domain (LAP) trophy was induced either by isopro- family. The encoded Erbin protein terenol administration or by aortic contains 17 leucine-rich repeats and constriction. In both models the lev- one PDZ domain. It binds to the un- el of Erbin was significantly de- phosphorylated form of the ERBB2 creased. The genetically engineered protein and regulates ERBB2 func- Erbin knockout mice rapidly devel- tion and localization. Erbin’s C-ter- oped decompensated cardiac hyper- minal PDZ domain is able to bind to trophy and following severe pres- ErbB2, a protein tyrosine kinase, sure overload, all of these mice died which is often associated with poor from heart failure (compared to only prognosis during the development about 30% mortality observed in the of skin cancer. Its N-terminal region control group). has been shown to affect the Ras sig- It is known that Erbin inhibited naling pathway by disrupting Ras- Ras-mediated activation of the extra- Raf interaction. cellular signal-regulated kinase Investigators at the Hebrew Uni- (ERK) by binding to the protein Soc- versity of Jerusalem (Israel; www. 2 suppressor of clear homolog huji.ac.il) looked at Erbin levels in (Shoc2). The data obtained during the absence of Erbin, Raf was phos- modulating ERK signaling. We de- humans and animals with and with- this study showed that ERK phosphorylated and bound to Shoc2, re- scribe a cardioprotective role for out cardiac hypertrophy. In addi- phorylation was enhanced in the sulting in ERK phosphorylation. Erbin, which suggests it is a poten- tion, they genetically engineered a heart tissues of the Erbin knockout The investigators concluded that, tial target for cardiac gene therapy.” line of mice to lack the Erbin gene. mice. Furthermore, Erbin associated “Erbin is an inhibitor of pathological Image: Left ventricular cardiac hyper- They reported in the April 22, with Shoc2 in both whole hearts cardiac hypertrophy, and this inhibi- trophy in short axis view (Photo cour- 2014, issue of the journal Proceed- and in cardiomyocytes, and that in tion is mediated, at least in part, by tesy of Patrick Lynch). Bioinformatics Application Designed to Look for New Uses for Old Drug y tying together cancer gene expression pat- drug gene signatures can indeed help us identify After identifying drugs that may reverse the BBterns with drug activity, scientists have found new candidate cancer therapeutics.” gene expression alterations linked with renal cell a possible cancer therapy concealed within an an- Renal cell cancer consists of multiple subtypes cancer, the investigators employed assays to timicrobial agent. that are likely caused by different genetic muta- measure the effect of the selected drugs on cells. Developing and evaluating a new anticancer tions. Over the years, Dr. Libermann has been This led to the identification of a small number of drug can cost a huge amount of money and take working to identify new disease markers and US Food and Drug Administration (FDA)-ap- many years of research. Finding an effective anti- therapeutic targets through gene expression sig- proved drugs that induced cell death in multiple cancer medication from the pool of drugs already natures of renal cell cancer that distinguish these kidney cancer cell lines. The researchers then as- approved for the treatment of other medical dis- diverse cancer subtypes from each other, as well sessed three of these drugs in an animal model of orders could slash a substantial amount of time as from healthy individuals. In this new study, he renal cell cancer and showed that the antimicro- and money from the process. and his colleagues were searching for agents that bial agent pentamidine (principally used for the Now, using a cutting-edge bioinformatics ap- might be effective against clear cell renal cancer, treatment of pneumonia) decreased tumor proach, a team led by investigators from Beth Is- the most common and highly malignant subtype growth and enhanced survival. Gene expression rael Deaconess Medical Center (BIDMC; Boston, of kidney cancer. Even though patients with early research using microarrays also identified the MA, USA; www.bidmc.org) has found that the stage disease can frequently be effectively treated genes in renal cell cancer that were counteracted approved antimicrobial drug pentamidine may through surgery, up to 30% of patients with renal by pentamidine. help in the treatment of patients with advanced cell cancer present with advanced stages of dis- “One of the main challenges in treating cancer kidney cancer. Described online May 1, 2014, in ease at the time of their diagnosis. is the identification of the right drug for the right the journal Molecular Cancer Therapeutics, To pursue this search, the investigators are us- individual,” clarified first author Luiz Fernando these new findings reveal how connecting cancer ing the Connectivity Map (C-MAP) database Zerbini, PhD, of the International Center for Ge- gene expression patterns with drug activity might (www.broadinstitute.org/cmap), a compendium netic Engineering and Biotechnology (Cape help advance cancer care. of gene expression data from human cancer cells Town, South Africa), adding that this bioinformat- “The strategy of repurposing drugs that are treated with hundreds of small molecule drugs. ics application could be an especially valuable currently being used for other indications is of sig- “C-MAP uses pattern-matching algorithms to en- lower-cost model in developing countries. nificant interest to the medical community as able investigators to make connections between The authors reported that their next phase of well as the pharmaceutical and biotech indus- drugs, genes and diseases through common, but the research will be to assess the potential of pen- tries,” said senior author Towia Libermann, PhD, inverse, changes in gene expression,” stated Dr. tamidine used in combination with the existing director of the Genomics, Proteomics, Bioinfor- Libermann. “It provided us with an exciting op- standard-of-care therapies to treat kidney cancer. matics and Systems Biology Center at BIDMC portunity to use our renal cell cancer gene signa- “Since the drugs we are evaluating are already and associate professor of medicine at Harvard tures and a new bioinformatics strategy to match FDA-approved, successful studies in preclinical Medical School (Boston, MA, USA). “Our results kidney cancer gene expression profiles from indi- animal models may enable us to rapidly move demonstrate that bioinformatics approaches in- vidual patients with gene expression changes in- these drugs into clinical trials,” added Dr. Liber- volving the analysis and matching of cancer and ducted by various commonly used drugs.” mann.

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CELL IMAGING SYSTEM FUME HOOD OPTICAL OXYGEN SENSOR GE Healthcare Hamilton Scientific ibidi The Cytell system is an intuitive benchtop instru- The Mistral features an increased sight line for im- The OPAL Optical O2 measurement system is de- ment equipped with onboard data analysis and vi- proved safety, a low profile, ergonomic airfoil for signed to measure the exact oxygen content di- sualization tools. It streamlines and simplifies rou- ease of use, and chain and sprocket drive mech- rectly in cells and tissues. The OPAL measure- tine assays such as cell cycle and cell viability, anism for improved performance and reliability. ment is noninvasive and occurs in real time, mak- and efficiently delivers accurate, high-quality, The line is available in a wide variety of sizes and ing it ideal for in vitro hypoxia conditions such as quantitative results. options to meet every laboratory need. 3-D cultures, spheroid models, and tissues.

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Metallopolymers Protect Penicillin-Like Antibiotics from Bacterial Beta-Lactamase ovel drug combinations that unite classical To correct this problem, investiga- NNpenicillin-like antibiotics with metallopoly- tors at the University of South Caroli- mers effectively kill bacteria, including “super- na (Columbia, USA; www.sc.edu) de- bugs” such as MRSA (methicillin-resistant Staphy- veloped an improved class of beta-lac- lococcus aureus) that had developed beta-lacta- tam antibiotics by conjugating classi- mase enzyme-based resistance to the antibiotics. cal penicillin-like antibiotics to cobal- Metallopolymers are a class of polymers with tocenium metallopolymers. metal atoms either in the backbone or at the side They reported in the March 17, chain. These polymers exhibit many unprecedent- 2014, online edition of the Journal of ed properties and functions that conventional or- the American Chemical Society that ganic polymers usually lack. Among metallopoly- these combinations exhibited a syner- mers, metallocene-containing polymers have at- gistic effect against MRSA by effi- tracted significant attention due to their unique ciently inhibiting activity of beta-lac- electrochemical, catalytic, and optical properties. tamase and effectively lysing bacterial year, around 100,000 patients die of bacteria-in- Metallocene-containing polymers are widely used cells. Various conventional beta-lactam antibi- duced infections,” said senior author Dr. Chuan- for redox active systems as recognition of ions and otics, including penicillin-G, amoxicillin, ampi- bing Tang, professor of chemistry and biochem- sugars and modification of electrodes. cillin, and cefazolin, were protected from beta-lac- istry at the University of South Carolina. “And the MRSA, a complex of multi-drug-resistant tamase hydrolysis via the formation of unique ion- problem is increasing because bacteria are build- Gram-positive bacterial strains, has proven espe- pairs between their carboxylate anions and cation- ing resistance. It is a really, really big problem, not cially problematic in both hospital and communi- ic cobaltocenium moieties. only for individual patients, but also for society.” ty settings by deactivating conventional beta-lac- “Instead of developing new antibiotics, here tam antibiotics, including penicillins, cephalo- we ask the question, “Can we recycle the old an- Image: The MRSA superbug (in yellow), often found sporins, and carbapenems, through various mech- tibiotics?” With traditional antibiotics like peni- in hospitals, is resistant to antibiotics and can lead to death, but a new polymer-antibiotic combo to deal anisms, resulting in increased mortality rates and cillin G, amoxicillin, ampicillin, and so on, can we with MRSA is in the works (Photo courtesy of the Na- hospitalization costs. give them new life?” In the United States every tional Institute of Allergy and Infectious Diseases). Melanoma Development Depends on the Activity of the RUNX2 Transcription Factor he transcription factor RUNX2 (runt-related ined the role of the RUNX2 transcription factor in tional activity and decreased migration of TTtranscription factor 2) has been found to play melanomagenesis. They reported in the March 31, melanoma cells, further suggesting a role of a critical role in melanomagenesis, the processes 2014, online edition of the journal Cancer Letters RUNX2 in melanoma cell migration. leading to development of the skin cancer, that the expression of transcriptionally active “Successful efforts to render transcription fac- melanoma. RUNX2 was increased in melanoma cell lines as tors “drugable” by interfering with different as- The RUNX2 gene is a member of the RUNX compared with normal human melanocytes. Using pects of their transcriptional activity make this family of transcription factors and encodes a nu- a melanoma tissue microarray, they showed that class of proteins attractive targets for therapy,” said clear protein with a Runt DNA-binding domain. RUNX2 levels were higher in melanoma cells as senior author Dr. Karine Cohen-Solal, assistant pro- This protein is essential for osteoblastic differentia- compared with nevic melanocytes. fessor of medicine at the Rutgers Cancer Institute. tion and skeletal morphogenesis and acts as a scaf- Genetic silencing of RUNX2 in melanoma cell “Exploring the role of RUNX2 in the development fold for nucleic acids and regulatory factors in- lines significantly decreased Focal Adhesion Kinase of melanoma is likely to reveal new mechanisms volved in skeletal gene expression. expression and inhibited cell growth, migration, driving melanoma progression and identify a target Investigators at the Rutgers Cancer Institute and invasion ability. Furthermore, the pro-hor- for novel antimelanoma agents, thereby opening (New Brunswick, NJ, USA; www.cinj.org) exam- mone cholecalciferol reduced RUNX2 transcrip- new avenues for the treatment of this disease.”

Bio Research International July-August/2014 18 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International Bioprinting 3D Technology Mimics Liver to Detoxify Blood anoengineers have developed a California, San Diego’s (UCSD; USA; NNthree-dimensional (3D)-printed www.ucsd.edu) nanoengineering device to act like the liver to remove Prof. Shaochen Chen devised a 3D- harmful toxins from the blood. The printed hydrogel matrix to hold device, which is designed to be used nanoparticles, forming a device that outside the body, similar to dialysis, mimics the function of the liver by utilizes nanoparticles to trap pore- sensing, attracting, and capturing forming toxins that can injure cellu- toxins channeled from the blood. lar membranes and are a major factor The device, which is in the proof- in disorders that result from stings, of-concept phase, replicates the struc- animal bites, and bacterial infections. ture of the liver but has a larger sur- The study’s findings were pub- face area designed to effectively lure lished May 8, 2014, in the journal and trap toxins within the device. In Nature Communications. Nanoparti- an in vitro study, the device totally cles have already been shown to be neutralized pore-forming toxins. effective at neutralizing pore-forming “One unique feature of this device is toxins in the blood, but if those that it turns red when the toxins are “This will inspire many new designs sels, in only seconds out of soft bio- nanoparticles cannot be effectively captured,” said the co-first author, for detoxification techniques since compatible hydrogels that contain digested, they can accumulate in the Xin Qu, who is a postdoctoral re- 3D printing allows user-specific or living cells. liver creating a risk of secondary poi- searcher working in Prof. Chen’s lab- site-specific manufacturing of highly soning, particularly among patients oratory. “The concept of using 3D functional products.” Image: A team led by nanoengineering who are already at risk of liver fail- printing to encapsulate functional professor Shaochen Chen has devel- Prof. Chen’s lab has already vali- oped a 3D device that, like a human liv- ure. To resolve this problem, a team nanoparticles in a biocompatible hy- dated the ability to print complex 3D er, removes toxins from the blood- of investigators, led by University of drogel is novel,” said Prof. Chen. microstructures, such as blood ves- stream (Photo courtesy of UCSD). Canada to Establish “Big Data” Cloud-Computing Facility for Cancer Research he Government of Canada announced CAD include Genome Canada, the Canada Foundation “Canada and many other nations around the TT7.3 million in funding for a collaboration – for Innovation (CFI), and the Canadian Institutes of world have already invested tremendous resources both in Canada and internationally – to develop Health Research (CIHR). in sequencing of thousands of cancer genomes, but tools that can effectively manipulate huge amounts The University of Chicago (IL, USA) is also pro- until now there has been no viable long-term plan for of data to help find cures for cancer. viding critical computing resources for the project. storing the raw sequencing data in a form that can be Recently developed technologies for genetic Furthermore, a large initial donation of genomic da- easily accessed by the research community. The Can- analysis have created almost unimaginable amounts ta will come from the International Cancer cer Genome ‘Collaboratory’ will open this incredibly of data, measured in petabytes. Genomic re- Genome Consortium, and brings together re- important data set to researchers from laboratories searchers are eager to analyze these data and iden- searchers from some 16 jurisdictions worldwide. large and small, enabling them to achieve new in- tify genetic clues that could point to new ways to The International Cancer Genome Consortium is sights into the causes of cancer and to develop inno- prevent or cure cancer. Such an effort, however, re- the largest worldwide coordinated effort to produce vative new ways to diagnose and manage the dis- quires thousands of high-performance computers a catalog of genetic structure of cancer organisms. ease,” noted Lincoln Stein, director, Informatics and working in tandem, along with the yet-unavailable Its 10-year goal is to characterize the genetic mate- Biocomputing Program, Ontario Institute for Cancer software tools that can coordinate such an intimi- rials from tumors in 500 patients for each of the Research, and professor, department of molecular ge- dating and complex task. major cancer types. netics, University of Toronto (Canada). Funded through Canada’s Natural Sciences and Engineering Research Council of Canada’s (NSERC; Ottawa, ON, Canada; www.nserc-crsng.gc.ca) Dis- covery Frontiers, the new project will develop effective new computing tools, so that researchers can study genetic data from thousands of cancers to learn more about how tumors develop, and which treatments work best. At the center of the project will be a new cloud- computing facility, the Cancer Genome Collaborato- ry (Ottawa, ON, Canada), capable of processing genetic profiles gathered by the International Cancer Genome Consortium (ICGC; www.icgc.org) from tumors in some 25,000 patients worldwide. The powerful new data-mining tools are expected to be available in 2015 for beta testing by selected cancer genomics and privacy researchers. The facility is planned to be opened to the wider research community in 2016. Researchers will be able to formulate questions about cancer risk, tumor growth, and drug treatments, and extract an analysis against the data. The NSERC initiated the project with a partner- ship among federal granting organizations that also

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PROTEIN ANALYSIS SYSTEM WEIGH MODULES WELL PLATE SHAKER Malvern Instruments Mettler Toledo MO BIO Laboratories The Zetasizer Helix is designed to enable the de- The SWB605 PowerMount weigh modules contin- The 96-well plate shaker features an adjustable tailed study of mechanisms or protein aggrega- uously monitor load cell performance, discovering parameter lock, memory keys for three standard tion. The system combines DLS technology with variances before they impact productivity. De- working programs, and automatic centering of Raman spectroscopy, and allows the accurate signed to be easy to install, the modules offer plates for easier, quicker, and safer handling. The measurement of protein size and structure from a rugged construction, built-in safety features, and shaker holds two 96-well plates, and lyses all cell single small volume sample. enable easier operation and maintenance. types when used with bead beating.

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Silly Putty Component Used to Help in Stem Cell Therapies he sponginess of the setting the researchers can adjust the stiff- TTwhere human embryonic stem ness of the surface they grow cells cells are growing, affects the type of on. Shorter posts are more rigid – specialized cells they will ultimately similar to an industrial carpet. Taller become, new research shows. Sci- ones are softer – more plush. entists persuaded human embryonic The scientists found that stem stem cells to convert into working cells they grew on the tall, softer mi- spinal cord cells more effectively by cropost carpets turned into nerve growing the cells on a soft, ultrafine cells much faster and more fre- carpet made of a key ingredient in quently than those they grew on the Silly Putty [a substance with unusu- stiffer surfaces. After 23 days, the al properties based on silicone poly- colonies of spinal cord cells – motor mers, used as a toy]. neurons that regulate how muscles The study’s findings were pub- move – that grew on the softer mi- lished online April 13, 2014, in the cropost carpets were four times journal Nature Materials. This re- more pure and 10 times larger than search is the first to directly link those growing on either traditional physical, instead of chemical, signals plates or rigid carpets. neurons from patients’ own cells. teins ferry chemical messages from to human embryonic stem cell dif- “This is extremely exciting,” At this point, they are examining the cell’s borders to deep inside it. ferentiation. Differentiation is the Prof. Fu said. “To realize promising how and whether the process could The pathway they narrowed in on, process of the source cells morphing clinical applications of human em- work, and they hope to try it in hu- called Hippo/YAP, is also involved into the body’s more than 200 cell bryonic stem cells, we need a better mans in the future. “Prof. Fu and in controlling organ size and both types that become bone, muscle, culture system that can reliably pro- colleagues have developed an inno- causing and preventing tumor nerves, and organs. duce more target cells that function vative method of generating high- growth. Jianping Fu, a University of well. Our approach is a big step in yield and high-purity motor neu- Prof. Fu reported that his find- Michigan (U-M; Ann Arbor, USA; that direction, by using synthetic rons from stem cells,” Prof. Feld- ings could also provide clues into www.umich.edu) assistant professor microengineered surfaces to control man said. “For ALS, discoveries like how embryonic stem cells differen- of mechanical engineering, noted mechanical environmental signals.” this provide tools for modeling dis- tiate in the body. “Our work sug- that the findings offer the potential Prof. Fu is collaborating with ease in the laboratory and for devel- gests that physical signals in the cell of a more effective way to guide physicians at the U-M Medical oping cell-replacement therapies.” environment are important in neu- stem cells to differentiate and poten- School. Eva Feldman, a professor of Prof. Fu’s findings go deeper ral patterning, a process where tially provide therapies for diseases neurology, studies amyotrophic lat- than cell counts. The researchers nerve cells become specialized for such as amyotrophic lateral sclerosis eral sclerosis (ALS), which para- verified that the new motor neu- their specific functions based on (also known as Lou Gehrig’s dis- lyzes patients as it kills motor neurons they obtained on soft microp- their physical location in the body,” ease), Huntington’s, or Alzheimer’s. rons in the brain and spinal cord. ost carpets showed electrical behav- he said. In the specially modified growth Researchers such as Prof. Feld- iors comparable to those of neurons system, the “carpets,” Prof. Fu and man believe stem cell therapies – in the human body. They also iden- Image: Researchers cultured stem his colleagues designed microscopic both from embryonic and adult va- cells on ultrafine carpets made of mi- tified a signaling pathway involved croscopic posts of a key ingredient in posts of the Silly Putty component rieties – might help patients grow in regulating the mechanically sen- Silly Putty (Photo courtesy of Ye Tao, polydimethylsiloxane to serve as the new nerve cells. The researchers sitive behaviors. A signaling path- Rose Anderson, Yubing Sun, and threads. By varying the post height, technique to try to generate fresh way is a route through which pro- Jianping Fu / University of Michigan).

Bio Research International July-August/2014 20 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International Novel Apparatus Mimics Human Digestive System for Oral Drug Studies team of British drug developers the control unit that monitored AAhas created an instrument that changes in pH of the solvent medi- mimics the human digestive system, um and, as appropriate, fed pH in- which will allow them to accurately creasing and/or pH reducing gas determine how orally administered from the tanks into the chamber. medications are dissolved and then The control unit was able to main- absorbed. Investigators at the Uni- tain a uniform pH during testing or versity of Huddersfield (United King- could be set to provide a dynamical- dom; www.hud.ac.uk) sought a way ly adjustable pH range, for example to study the behavior of oral drugs in to three or more different pH levels the digestive tract that would avoid in order to test the performance of a the differences between the diges- drug carrier at different levels of tive systems of humans and laborato- acidity or alkalinity. ry animals. “By minimizing human trials we To this end, they developed an would reduce the cost of develop- apparatus for testing drug solubility ment, which is then charged to pa- that included a chamber for holding tients when the drug comes to the Image: The testing device includes a chamber for holding a solvent medium plus a solvent medium – often a bicar- market – if the development costs are a pH probe and a control unit. This monitors changes in the pH of the solvent bonate based buffer system – as well lower, then we can make new drugs medium in order to test the performance of a drug carrier at different levels of acid- as a pH probe connected to tanks of more affordable,” said Dr. Hamid Mer- ity or alkalinity, mimicking the conditions of the gastrointestinal tract. The device is particularly suitable for testing and developing dosage forms for oral delivery of carbon dioxide and helium. chant, senior lecturer of pharmaceu- drugs and can also simulate the variability between individuals (Photo courtesy of The heart of the apparatus was tics at the University of Huddersfield. Dr. Hamid Merchant / University of Huddersfield). Simulation Gives Clues About Forces Underlying Fundamental Cellular Processes esearchers have developed a simulation model slide over one another exerting a force that we can RRresulting in clues to physical conditions that control.” The force exerted by the filaments is the help drive cell division and motility. The results variable that competes with another force, the sur- may also hint at conditions that helped facilitate the face tension that prevents the membrane surround- original transition from inanimate to living matter. ing the droplet from collapsing. This “competition” Active droplets of filamentous material enclosed generates a flow in the fluid surrounding the in a lipid membrane are the main cell-like charac- droplet, and the droplet is in turn propelled by this teristics modeled in a program, developed by physi- self-generated hydrodynamic flow. When the flow cists Luca Giomi and Antonio DeSimone of the In- becomes very strong, the droplet deforms to the laws governing these phenomena could be very ternational School for Advanced Studies (SISSA; point of dividing: “When the force of the flow pre- simple. Observations like ours can prepare the way Scuola Internazionale Superiore di Studi Avanzati; vails over the force that keeps the membrane to- for the creation of functioning artificial cells, and Trieste, Italy; www.sissa.it), for numerical simula- gether we have ‘cellular’ division,” said Dr. DeSi- not only,” said Dr. Giomi. “Our work is also useful tions to investigate the mechanics of “simplified” mone, director of the SISSA mathLab, SISSA’s math- for understanding the transition from non-living to pre-cell structures. The simulations indicated a ematical modeling and scientific computing labora- living matter on our planet.” Chemists and biolo- spontaneous emergence of features reminiscent of tory. gists who study the origin of life lack access to cells living material – of cell-like motility and division. The study, described in the April 10, 2014, on- that are sufficiently simple. “Even the simplest or- The model mimics some of the physical proper- line issue of the journal Physical Review Letters, is ganism existing today has undergone billions of ties of cells: “Our ‘cells’ are a bare bones represen- a step forward toward creating functional artificial years of evolution, and will always contain fairly tation of a biological cell, which normally contains cells and toward a better understanding of the first complex structures,” noted Dr. Giomi. microtubules, elongated proteins, enclosed in an es- passages from which life has developed: “Acquiring sentially lipid cell membrane,” said Dr. Giomi; “The motility and the ability to divide is a fundamental Image: Cell-like features in computer-simulated active filaments contained in the ‘cytoplasm’ of our cells step for life and, according to our simulations, the droplets (Photo courtesy of SISSA).

Resveratrol Interacts with Estrogen Receptor to Modulate Inflammation molecular mechanism has been identified that whereas white wine is fermented after the skin has estrogen receptor-alpha (ERalpha) ligand to modu- AAexplains how the wine and grape product been removed. Resveratrol came to scientific atten- late the inflammatory response but not cell prolif- resveratrol modulates the inflammatory response tion during the mid-1990s as a possible explanation eration. A crystal structure of the ERalpha ligand- by interacting with estrogen receptor-alpha. for the “French Paradox” – the low incidence of binding domain (LBD) as a complex with resvera- Resveratrol (trans-3,5,4’-trihydroxystilbene), a heart disease among the French, who eat a relative- trol revealed a unique perturbation of the coactiva- compound found largely in the skins of red grapes, ly high-fat diet. Since then, it has been promoted by tor-binding surface, consistent with an altered is a component of Ko-jo-kon, a form of oriental manufacturers and examined by scientific re- coregulator recruitment profile. Gene expression medicine used to treat diseases of the blood vessels, searchers as an antioxidant, an anticancer agent, analyses revealed significant overlap of TNFalpha heart, and liver. Red wine contains between 0.2 and a phytoestrogen. (tumor necrosis factor alpha) genes modulated by and 5.8 mg/L of resveratrol, depending on the Investigators at The Scripps Research Institute resveratrol and estradiol. In addition, the ability of grape variety, while white wine has much less – the (Jupiter, FL, USA; www.scripps.edu) reported in resveratrol to suppress interleukin-6 transcription reason being that red wine is fermented with the the April 25, 2014, online edition of the journal was shown to require ERalpha and several ERalpha skins, allowing the wine to absorb the resveratrol, eLife that resveratrol acted as a pathway-selective coregulators.

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DUCTLESS FUME HOOD SPECTROMETER DATA ANALYSIS SOFTWARE Mystaire Ocean Optics Oxford Gene Technology The Aura Elite includes the latest in microproces- The Maya LSL is a combination of a back-thinned The latest version (4.5.3) of CytoSure Interpret sor-based controls, and monitors fume hood per- CCD array detector and low stray light optical de- software is a powerful and easy-to-use package formance constantly while logging the energy sign resulting in high-sensitivity, high-throughput for the analysis of aCGH data. The software offers consumed for display to the end user. This feature performance. The Maya LSL is considered ideal a combination of advanced features, and allows allows lab staff more visibility to monitor and confor life science applications ranging from chemical users the choice of standardized or customized serve energy when the hood is not in use. catalysis to Raman analysis. user-defined data analysis.

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Big Data’s Direct Coupling Analysis Reveals Clues About Molecular Protease Machines esearchers have merged genetic and structur- Morcos and Onuchic with colleagues at the Uni- RRal data in a Big Data attempt to solve one of versity of California, San Diego (UCSD; USA; the most fascinating mysteries in biology: how www.ucsd.edu), and the Pierre and Marie Curie proteins perform the regulatory processes in cells University (Paris, France; www.upmc.fr). DCA upon which all life depends. looks at the genetic roots of proteins to see how The daily life of a motor molecule involves eat- amino acids – the “beads” in the unfolded protein ing and excreting damaged proteins and convert- strands – co-evolved to influence the way a pro- ing them into harmless peptides ready for dispos- tein folds. Each bead carries an inherent energy al. Without these garbage bins, the Escherichia that contributes to the strand’s unique energy to- coli bacteria they attend to would die. Biophysi- pography, which decrees how it folds into its func- cists from Rice University (Atlanta, GA, USA; tional state. www.rice.edu) used a protease called an FtsH- Proteins, even after they fold, are in constant AAA hexameric peptidase as a model to examine motion, acting as catalysts for countless bodily calculations that combine genetic and structural functions. They can combine into larger molecu- data. lar machines that grab other molecules, “walk” Dr. José Onuchic, a biologic physicist, and post- their payloads within a cell or cause muscles to doctoral researchers Drs. Biman Jana and Faruck contract. One such biomachine is FtsH (filamen- Morcos published their new findings March 2014 tous temperature-sensitive H), a membrane- in the Royal Society of Chemistry journal, Physi- bound molecule in E. coli made of six protein cal Chemistry Chemical Physics. The study is the copies that form two connected hexagonal rings. first successful attempt to feed data through their The molecule attracts and degrades misfolded year-old skill of crystallography are making better computational technique to describe the complex proteins and other cellular waste pulling them in structure-based models available as well. “Even if activity of a large molecular machine formed by through one ring, which closes similar to a shut- the mathematical framework was ready and we proteins. Ultimately, understanding these ma- ter of a camera and traps the proteins. They are had crystallographic data for this motor protein in chines will help researchers design drugs to treat sliced apart as they leave through the other ring. the 1990s, there weren’t enough sequences avail- diseases including cancer, the focus of Rice’s Cen- Through molecular simulations using struc- able until the 2000s,” Dr. Morcos said. “Now we ter for Theoretical Biological Physics. ture-based models and the discovery using DCA have all the pieces converging.” “Structural techniques like X-ray crystallogra- of probable couplings in the genetic source of the Dr. Morcos noted that by better determining phy and nuclear magnetic resonance have proteins, the researchers found evidence to sup- essential motor proteins in bacteria will be impor- worked quite well to help us understand how port the hypothesis of a “paddling” process in the tant as researchers begin to apply DCA to opti- smaller proteins function,” Dr. Onuchic stated. X- molecule that Dr. Morcos described as a collapse mize human healthcare. “For us, the most excit- rays only take snapshots of constantly moving proof the two rings once waste found its way inside. ing part is that we’re now able to tackle really big teins, he said, “but functional proteins, big protein “First the ring pore closes to grab the protein; systems,” he said. complexes and molecular machines have multiple then the molecule flattens,” he said. “Then when conformations. Computational models are also the motor is flat, the rings open to release the pep- Image: Co-evolved mutations in genetic sequences that code proteins show researchers how a protein is useful, but to understand the full dynamics of tides and the molecule expands again to restart likely to fold and what forms it may take as it carries these large proteins, where a lot of the interesting the cycle.” out its function. Scientists used the technique called biology takes place, we have to supplement them DCA would do little without the deluge of da- direct coupling analysis in combination with struc- with more information.” ta available since the ability to scan entire ture-based models to find a previously hidden con- formation of a molecular motor responsible for de- That information comes from direct coupling genomes became possible, and even routine, in grading misfolded proteins in bacteria (Photo cour- analysis (DCA), a statistical tool developed by Drs. recent years. Recent developments in the 100- tesy of Faruck Morcos / Rice University).

Bio Research International July-August/2014 22 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International Reduced Elafin Levels Associated with Celiac Disease Bowel Inflammation evels of the enzyme elafin, an tissues taken from human small in- LLendogenous serine protease in- testines. The degree of deamidation hibitor, were lower in the small in- of the 33-mer gliadin peptide was testinal epithelium of patients with analyzed by liquid chromatogra- active celiac disease (CD) as com- phy-mass spectrometry. To study pared to similar tissue from control the effects of elafin on a mouse patients. model of celiac disease, the protein Celiac disease is an immune dis- was delivered to the intestine of order that occurs in susceptible in- gluten-sensitive mice using a re- dividuals when foods that contain combinant Lactococcus lactis vec- gluten and its derivative, the highly tor. immunogenic gliadin peptide, trig- Results published in the April 8, ger an immune response that leads 2014, online edition of the Ameri- to destruction of the intestinal lin- can Journal of Gastroenterology re- ing, abdominal pain, changes in vealed that elafin expression in the bowel habits, malnutrition and oth- small intestinal epithelium was low- by the L. lactis vector normalized that will protect patients with celiac er symptoms that include anemia er in patients with active CD com- inflammation and improved perme- disease from these accidental con- and neurological problems. pared with control patients. In vit- ability. taminations. The possibility of elafin Investigators at McMaster Uni- ro, elafin significantly slowed the ki- Maintaining a gluten-free diet is administration or replacement as a versity (Hamilton, ON, Canada; netics of the deamidation of the 33- far from simple, as gluten is found new adjuvant therapy to the gluten www.mcmaster.ca) used immuno- mer peptide to its more immuno- not only in foods but as low cost free diet would add flexibility to a fluorescence techniques to exam- genic form. Treatment of gluten- filler in the cosmetic and pharma- restrictive lifelong diet, and in- ine the role of elafin in CD using sensitive mice with elafin delivered ceutical industries as well. crease patients’ quality of life and “People who have to strictly potentially accelerate the healing of Retinoic Acid Prevents Precancerous Breast avoid gluten for life often find this celiac lesions.” very difficult due to these hidden Cells from Progressing to Full-Blown Cancer sources,” said senior author Dr. Ele- Image: A biopsy of small bowel showing celiac disease manifested by etinoic acid, a derivative of vita- of one micromolar ATRA, the trMCF na Verdu, associate professor of blunting of villi, crypt hyperplasia, and RRmin A, was found to prevent pre- clone 11 cells showed tubules in col- medicine at McMaster University. lymphocyte infiltration of crypts (Pho- cancerous breast cells from progress- lagen. Gene expression studies “There is a great need for a therapy to courtesy of Wikimedia Commons). ing to full-blown cancer but did not showed that 207 genes upregulated have any effect on breast tumor cells. in transformed trMCF clone 11 cells Investigators at Thomas Jefferson were downregulated after one micro- University (Philadelphia, PA, USA; molar ATRA treatment to levels com- www.jefferson.edu) worked with a parable to those found in the normal novel breast cancer model that had breast epithelial cells MCF-10F. Fur- been developed by treating MCF-10F thermore, 236 genes that were down- human normal breast epithelial cells regulated in trMCF clone 11 were up- with a high dose of estradiol. The regulated after one micromolar ATRA model system consisted of four dis- treatment to similar levels shown in tinct cell lines which demonstrated a normal epithelial cells. These 443 progressive neoplastic transforma- genes defined a signature of the ATRA tion: MCF-10F, normal stage; trMCF, reprogramming effect. transformed MCF-10F; bsMCF, inva- Results published in the March sive stage; and caMCF, tumorigenic 21, 2014, edition of the Internation- stage. In three-dimensional cultures, al Journal of Oncology showed that MCF-10F cells formed tubules resem- one micromolar ATRA was able to re- bling the structures in the normal differentiate transformed cells at ear- mammary gland. After treatment ly stages of the neoplastic process and with estradiol, these cells formed antagonistically regulate breast can- tubules and spherical masses, which cer associated genes. On the other were indicative of transformation. hand, the invasive and tumorigenic In the current study the investiga- cells did not show any changes in tors evaluated the effect of all trans- morphology after ATRA treatment. retinoic acid (ATRA) at different “It looks like retinoic acid exerts ef- stages of neoplastic transformation. fects on cancer cells in part via the Retinoids have been used as potential modulation of the epigenome,” said chemotherapeutic or chemopreven- senior author Dr. Sandra V. Fernandez, tive agents because of their differen- assistant research professor of medical tiative, antiproliferative, proapoptot- oncology at Thomas Jefferson Univer- ic, and antioxidant properties. sity. “We were able to see this effect of Cells that only formed spherical retinoic acid because we were looking masses in collagen were isolated (trM- at four distinct stages of breast cancer. CF clone 11) and treated with ATRA. It will be interesting to see if these re- After treatment with a concentration sults can be applied to patients.”

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MULTIPHOTON EXCITATION SYSTEM MASS SPECTROMETRY PRODUCTS ELECTROPHORESIS SYSTEM Olympus Owlstone PerkinElmer The FluoView FVMPE-RS is designed to enable The UltraFAIMS series of products was devel- The LabChip GX Touch features exact sizing and high-precision, ultra-fast scanning and excitation. oped to enhance mass spectrometry by quickly quantitation of DNA fragments, along with com- The system allows researchers to see deep with- simplifying complex mass spectra, separating iso- plete assessment of RNA quality for better gene in specimens, take measurements at the highest baric ions, and reducing background. The Ultra- expression data. The flexible system offers 96- speeds, and capture images, even when working FAIMS miniaturized chip-based FAIMS platform is and 384-well compatibility, and accuracy with res- under the most demanding conditions. considered ideal for a wide range of applications. olution down to 5 bp and sensitivity of 0.1 ng/µL.

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Penny Contact Lenses Created from Clear Liquid ne droplet of clear liquid can gel-like material – a simple and in- OObend light, acting as a lens. expensive approach that avoids Now, by utilizing this well-known costly or complicated machinery. phenomenon, researchers have de- “What I did was to systematically veloped a new process to create in- fine-tune the curvature that’s expensive, high quality lenses that formed by a simple droplet with should cost less than USD 0.01 the help of gravity, and without apiece. any molds,” he explained. Because the lenses being so in- Although scientists have long expensive, they can be used in a known that a droplet can act as a variety of applications, including lens, no one tried to see how good tools to detect diseases in the field, a lens it could be. Now, the team scientific research in the lab and has developed a process that push- optical lenses and microscopes for es this idea to its limits, according education in classrooms. to the researchers. All that is re- “What I’m really excited about quired is an oven, a microscope is that it opens up lens fabrication glass slide, and a common, gel-like three orders of magnitude lower in lenses could be used in the lab as technology,” stated Dr. Steve Lee silicone polymer called polydi- cost. “We’re quite surprised at the implantable lenses that biologists from the Research School of Engi- methylsiloxane (PDMS). First, a magnification enhancement using can use to study cells in vivo. The neering at the Australian National small amount of PDMS is dropped such a simple process,” he noted. high cost of conventional lenses University (ANU; Canberra, Aus- onto the slide. Then, it is baked at Their low cost – low enough to usually dissuades scientists from tralia; www.anu.edu.au) of the 70 °C to harden it, creating a base. make them disposable – allows for implanting them into mice, he renew technique, which he and his Then, another squirt of PDMS is a variety of uses. In particular, the ported. The lenses would also be colleagues described in an article dropped onto the base and the researchers have constructed a lens suitable for hobbyists or as part of published April 24, 2014, in The slide is flipped over. Gravity pulls attachment that converts a smart- low cost mobile microscopes that Optical Society’s (OSA) open-access the new droplet down into a para- phone camera into a dermascope, a can be distributed to children and journal Biomedical Optics Express. bolic shape. The droplet is baked tool to diagnose skin diseases such others for educational or outreach Many conventional lenses are again to solidify the lens. More as melanoma. Whereas common purposes, he added. “Simple optics made the same way lenses have drops can then be added to hone dermascopes can cost USD 500 or can be very powerful.” been made since Isaac Newton’s the shape of the lens that also more, the phone version costs ap- So far, the researchers cannot day – by grinding and polishing a greatly increases the imaging qual- proximately USD 2. The new der- make lenses much bigger than 1.27 flat disk of glass into a specific ity of the lens. “It’s a low cost and mascope, which was made using a cm in diameter. But to expand the curved shape. Others are produced easy lens-making recipe,” Dr. Lee three-dimensional (3D) printer and range of applications, the investiga- with more sophisticated methods, said. is designed for use in rural areas or tors are now fine-tuning the such as pouring gel-like materials The researchers made lenses developing countries, is slated to be process to make lenses as large as molds. But both approaches can be about a few millimeters thick with commercially available in just a few 5.08 cm and increasing the lens’s costly and complicated, according a magnification power of 160 times months, according to Dr. Lee. A optical performance. to Dr. Lee. With the new technolo- and a resolution of about 4 mi- similar smartphone-based tool can gy, the researchers harvest solid crometers – two times lower in op- also help farmers identify pests out Image: A set of droplet lenses on a microscope coverslip held up by ANU lenses of differing focal lengths by tical resolution than many commer- in their fields. researcher Steve Lee (Photo cour- suspending and curing droplets of a cial microscopes, but more than Dr. Lee also foresees that the tesy of Stuart Hay).

Bio Research International July-August/2014 24 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International Bone Marrow-on-a-Chip Designed to Evaluate New Drugs, Radiation Toxicity ew organ-on-a-chip technology has been recognized internationally circulation the tissue would experi- NNis providing scientists with an for its potential to replace animal ence in the body. Marrow in the de- important new tool to assess the ef- testing of new drugs and environ- vice remained healthy for up to one fects of new drugs and toxic agents mental toxins, and as a new way for week – long enough, typically, to on whole bone marrow. The device, scientists to model human disease. test the toxicity and effectiveness of nicknamed “bone marrow-on-a- To build organ chips, the re- a new drug. chip,” was developed by scientists searchers have combined multiple Bone marrow-on-a-chip could al- from Harvard University’s Wyss In- types of cells from an organ on a mi- so generate blood cells, which could stitute for Biologically Inspired Engi- crofluidic chip, while gradually sup- circulate in an artificial circulatory neering (SEAS; Boston, MA, USA; plying nutrients, removing waste, system to supply a network of other http://wyss.harvard.edu), and re- and applying mechanical forces the organs-on-chips. The US Defense Image: Microscopic view of the engi- produces the functions, structure, tissues would face in the body. But Agency Advanced Research Projects neered bone with an opening expos- ing the internal trabecular bony net- and cellular composition of bone bone marrow is so complicated that Agency (DARPA) is also currently work, overlaid with colored images of marrow, a complicated tissue that they needed a new approach to providing funds to the Wyss Insti- blood cells and a supportive vascular until now could only be studied in- mimic organ function. tute to develop an interconnected network that fill the open spaces in the tact in living animals, institute re- This complexity arises because network of ten organs on chips to bone marrow-on-a-chip (Photo courtesy of James Weaver / Harvard Uni- searchers reported in the May 4, bone marrow has an essential rela- study complex human physiology versity, Wyss Institute for Biologically 2014, online issue of the journal Na- tionship with bone. Marrow sits in- outside the body. Inspired Engineering). ture Methods. side trabecular bone – a solid-look- Specifically, the device could be ing type of bone with a porous, hon- used to develop safe and effective eycombed interior. Some areas are approaches to prevent or treat radia- warmer, some cooler; some are oxy- DISTRIBUTORS INVITED TO APPLY tion’s deadly effects on bone mar- gen-rich, others oxygen-starved – row without resorting to animal and the dozen or so cell types each Your Source for Sterilization Accessories testing, a challenge that is being pur- have their own preferred sites. To sued at the Institute with funding add complexity, bone marrow cells THERMO support from the US Food & Drug communicate with each other by se- RESISTANT Administration (FDA). In an initial creting and sensing a range of bio- GLOVES test, the engineered bone marrow, molecules, which act locally to tell Up to 37 cm 2014 CATALOG similar to human marrow, shrunk in them whether to live, die, specialize in length AVAILABLE response to radiation unless a drug or multiply. known to prevent radiation poison- Specifically, the researchers STERILIZABLE INSTRUMENT ing was present. packed dried bone powder into an & WORK-SURFACE MATS TURBOTURBO WASHINGWASHING The bone marrow-on-a-chip in open, ring-shaped mold the size of MACHINES TRAYS the future could also be employed to a coin battery, and implanted the Thermo-Resistant (-60 °C to 300 °C) Fully Washable & Flexible maintain a cancer patient’s own mar- mold under the skin on the ani- Suitable for central sterilization services row temporarily while he or she un- mal’s back. After eight weeks, they Sterilizable derwent marrow-damaging treat- surgically removed the disk-shaped Heavy Silicone Cover & Transport Tablet

ments such as radiation therapy or bone that had formed in the mold SILICONSILICON INSTRUMENTINSTRUMENT MATMAT MICRO INSTRUMENT MAT high-dose chemotherapy. “Bone and examined it with a specialized marrow is an incredibly complex or- computed tomography (CT) imag- Front Back gan that is responsible for producing ing scanner. The scan revealed a all of the blood cell types of our body, honeycomb-like structure that and our bone marrow chips are able looked the same as natural trabecu- to recapitulate this complexity in its lar bone. WASHING TRAYS MAT WASHING TRAYS MAT entirety and maintain it in a func- When they stained the tissue and tional form in vitro,” said Don Ing- examined it under a microscope, ber, MD, PhD, founding director of the marrow was packed with blood

the Wyss Institute, a professor of vas- cells, similar to a marrow from a liv- Front Back Front Back cular biology at Harvard Medical ing mouse. Furthermore, when the School and Boston Children’s Hospi- researchers sorted the bone marrow NEW! NEW! tal, and a professor of bioengineering cells by type and checked their SILICONESILICONE WASHINGWASHING MA-MA- at the Harvard School of Engineering numbers, the combination of differ- CHINECHINE TRAYTRAY && TABLETTABLET and Applied Science (SEAS; http:// ent types of blood and immune cells SILICONESILICONE TABLETTABLET ANDAND seas.harvard.edu), and senior author in the modified bone marrow was Exchangable Net STEELSTEEL COVERCOVER NETSNETS of the study. identical to that in a mouse thigh- Dr. Ingber leads a large effort to bone. develop human organs-on-chips. Up To maintain the engineered bone STERILIZABLESTERILIZABLE to now, Wyss Institute investigators marrow outside of a living animal, WORK-SURFACE MATS have constructed lung, heart, kid- the researchers surgically removed Exchangable Nets 100% Silicone Size: 2400 x 1200 mm (3 mm thick) ney, and gut chips that reproduce the engineered bone from mice, basic characteristics of organ func- then placed it in a microfluidic de- tion, and they have more organs-on- vice that steadily supplied nutrients VICOTEX S.A. chips in the works. The technology and removed waste to mimic the Place de la Gare 1 • 1009 Pully • Switzerland Tel: (41) 21-728-4286 • Fax: (41) 21-729-6741 E-Mail: [email protected] Vicolab.TradeMed.com Bio Research International 25 July-August/2014 LINKXPRESS COM BRI-08-14 125 To receive prompt and free information on products, log on to PRODUCT NEWS www.LinkXpress.com or fill out reader service form located on last page

LIBRARY PREP KITS POLYETHYLENE BAGS BLENDER BAGS Rubicon Genomics Sartorius Stedim Biotech Seward The PicoPLEX DNA-seq kits are designed to am- The Flexsafe line of polyethylene bags enables The Stomacher bag range fulfills all applications plify DNA to yield a highly reproducible NGS- the implementation of single-use bioprocessing from sample blending, straining and storage, in- ready library from a single cell with input concen- throughout all steps of drug manufacture. The cluding bags intended for extensive blending, and trations of six picograms or less. The easy-to-use, bags are safe and easy to use, and offer users small samples for life science applications. The reliable single-cell prep kits are intended for use consistent cell growth, as well as enhanced ro- sterile bags are designed to withstand extensive with Illumina’s NGS platforms. bustness and flexibility. blending without tears or perforations.

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Unanticipated Link Found Between Cell Suicide and Long Life any health professionals believe that free the correct manner by free radicals, in reality MMradicals, the occasionally toxic molecules strengthens the cell’s defenses and increases its generated by the body as it processes oxygen, are longevity. Their findings were published online the cause behind aging. However, a number of May 8, 2014, in the journal Cell. “People believe studies recently have generated evidence that the that free radicals are damaging and cause aging, contrary may be true. but the so-called ‘free radical theory of aging’ is in- Researchers from McGill University (Montreal, correct,” said Siegfried Hekimi, a professor in QC, Canada; www.mcgill.ca) have taken this find- McGill’s department of biology, and senior author ing further by showing how free radicals promote of the study. “We have turned this theory on its longevity in a research model organism, the head by proving that free radical production in- roundworm Caenorhabditis elegans. Unexpect- creases during aging because free radicals actually apoptotic signaling. But that doesn’t mean it will edly, the scientists discovered that free radicals combat – not cause – aging. In fact, in our model be easy.” (i.e., oxidants) act on a molecular mechanism organism we can elevate free radical generation Triggering pro-longevity apoptotic signaling that, in other surroundings, instructs a cell to kill and thus induce a substantially longer life.” could be especially critical in neurodegenerative itself. The findings have significant ramifications. disorders, according to Prof. Hekimi. “In the brain Apoptosis is a process by which injured cells “Showing the actual molecular mechanisms by the apoptotic signaling might be particularly tilted commit suicide in a range of circumstances: to which free radicals can have a pro-longevity effect toward increasing the stress resistance of dam- avoid inducing autoimmune disease, to avoid be- provides strong new evidence of their beneficial aged cells rather than killing them. That’s because coming cancerous, or to kill off viruses that have effects as signaling molecules,” Prof. Hekimi said. it is harder to replace dead neurons than other invaded the cell. The key molecular mechanism “It also means that apoptosis signaling can be used kinds of cells, partly because of the complexity of by which this occurs is well conserved in all ani- to stimulate mechanisms that slow down aging. the connections between neurons.” mals, but was first discovered in C. elegans – a Since the mechanism of apoptosis has been exten- finding that earned a Nobel Prize. sively studied in people, because of its medical im- Image: The roundworm Caenorhabditis elegans, used as an experimental model organism for re- The McGill University researchers discovered portance in immunity and in cancer, a lot of phar- searchers who showed how free radicals promote that this same mechanism, when stimulated in macological tools already exist to manipulate longevity (Photo courtesy of McGill University). Experimental Drug Protects Animal Model from Measles-Like Virus orking with an animal model that mimics ate the experimental drug ERDRP-0519, which tar- had recovered from CDV infection demonstrated a WWmeasles in humans, a team of molecular virol- gets the viral RNA polymerase. This enzyme is re- robust immune response and were protected against ogists has verified that a novel antiviral drug may quired for replication of the virus, as it catalyzes the re-challenge with a lethal CDV dose. complement the currently used vaccine and lead to synthesis of a complementary strand of RNA from The investigators stated that the drug is not in- eradication of the disease. the original viral RNA template. tended as a substitute for vaccination, but as an addi- To better study the measles virus under laborato- Results reported in the April 16, 2014, issue of tional weapon in a concerted effort to eliminate the ry conditions investigators at Georgia State Universi- the journal Science Translational Medicine revealed disease. “The emergence of strong antiviral immunity (Atlanta, USA; www.uga.edu) and colleagues at that prophylactic oral drug treatment of the ferrets ty in treated animals is particularly encouraging, Emory University (Atlanta, GA, USA; www. protected them from a lethal dose of CDV adminis- since it suggests that the drug may not only save an emory.edu) and the Paul-Ehrlich Institute (Langen, tered intranasally. Ferrets that received the drug after infected individual from disease but contribute to Germany; www.pei.de) used zoonotic Canine dis- having been infected with the same dose of virus closing measles immunity gaps in a population,” said temper virus (CDV), which induces a disease in fer- showed low-grade viral loads, remained asympto- senior author Dr. Richard Plemper, professor in the rets with 100% lethality. matic, and recovered from infection, whereas con- center for inflammation, immunity, and infection at The investigators used the ferret model to evalu- trol animals succumbed to the disease. Animals that Georgia State University.

Bio Research International July-August/2014 26 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International Project to Move Engineered Tissue and Organs from Lab to the Bedside or Operating Room s developments in lab-created organs and tis- mass generation of precise parts that are specific AAsues continue to advance, the challenge be- to each individual recipient. The development en- comes how to translate the technology from the tails combining the cells and a scaffold, or a mod- laboratory to the operating room. Two US univer- el that forms the essential shape. The support sities are now exploring manufacturing platforms structure is designed to gradually dissolve after to mass produce customized engineered tissues implantation in the body. At the same time, the and organs. scaffolding material is being absorbed by the body, Developing a way to scale up personalized lab- and the cells lay down materials to form a perma- created organs and tissues would benefit patients nent support structure, progressively replacing the volving manufacturing engineers early on in the bi- around the world who must wait for donated or- engineered scaffold with a new organ. ological research phase is vital to achieving com- gans to receive transplants. North Carolina (NC) Leading corporate and education specialists in mercialization,” said Dr. Starly. “NC State ISE re- State University’s (Raleigh, NC, USA; www.ise.nc- medicine, engineering, and science gathered at views the scientific process for growing tissue su.edu) industrial and systems engineering depart- this year’s Regenerative Medicine Foundation cells, and then applies 3D technologies and algo- ment (NC State ISE) engineers are partnering Conference, May 5-7, 2014, held in San Francis- rithms to automate it, so a very sensitive biological with biomedical scientists at the Wake Forest In- co (CA, USA), to share firsthand accounts of their process can be replicated safely and effectively.” stitute for Regenerative Medicine (WFIRM; Win- visions and challenges of bio-tissue manufactur- Dr. Anthony Atala, director of WFIRM and NC ston-Salem, NC, USA; www.wakehealth.edu/ ing. Dr. Binil Starly, director of NC State ISE’s lab- State ISE advisory board member, moderated a WFIRM). Together, the institutions are creating oratory for engineering biological tissue systems, panel on the marketing of regenerative medicine advancements in 3D technology, computer-aided uses bioprinting to devise ways for mass produc- therapies at the conference. WFIRM scientists modeling and intelligent automation to print tis- ing engineered tissue and also shared data about have developed lab-grown organs, such as blad- sues and organs for patients. With their focus on these latest developments, including a patent- ders, vaginal organs, and urine tubes successfully precision, computer modeling and three-dimen- pending process, which is collaboration between used in patients. sional (3D) printing will help scientists scale up WFIRM and NCSU, for providing replacement the tissue engineering processes currently being skin for burn victims. Image: Laboratory-grown vaginas. The procedure offers hope to women with congenital conditions in done manually. “It is one thing to be able to grow an organ but which the vagina and uterus are underdeveloped The future of organs-on-demand requires the another to take that ability to the bedside, so in- (Photo courtesy of Francois Lenoir / Reuters). 3D Test Reduces Dependence Novel Technique Allows Genome On Lab Animals for Testing Sequencing of Single Malaria Cells Asthma and Allergy Agents recently developed technique for n a recent study, scientists report that they’ve de- AAanalyzing the genome of a malaria IIveloped a simple, three-dimensional (3D) laborato- parasite within a single red blood cell is ry technique to test asthma and allergy medications expected to aid in the understanding of that mimics what occurs in the body, which could the molecular cell biology of these or- help reduce the need for animal testing. ganisms and in the design of new drugs Dr. Amir Ghaemmaghami and colleagues from the to prevent their growth and spread. University of Nottingham (UK; www.nottingham. Investigators at the Texas Biomed- ac.uk) noted that respiratory disorders, such as asth- ical Research Institute (San Antonio, ma and allergies, are becoming more common. These USA; http://txbiomed.org) combined conditions affect the lungs and the airway leading to advanced cell sorting technology and the lungs, making it difficult to breathe. Respiratory whole-genome amplification (WGA) to symptoms lead to expensive hospital visits, as well as generate high-quality DNA samples absences from work and school. Improved agents from parasite-infected red blood cells could provide better relief, but before giving new (RBCs) for genotyping and next-gener- medicines to people, researchers must first test them ation sequencing. They optimized this in animals – an expensive and arduous process. approach through analysis of more limited our understanding of malaria parasite biolo- Sometimes, researchers will use 2D tests in which than 260 single-cell assays, and quantified accuracy gy” said senior author Dr. Ian Cheeseman, a post- they apply the drug to a layer of human cells in a lab by decomposing mixtures of known parasite geno- doctoral scientist in the genetics department of the dish instead, but this is not a satisfactory way to tell types and obtaining highly accurate (> 99%) single- Texas Biomedical Research Institute. “It is like try- how a pharmaceutical agent will perform in a whole cell genotypes. ing to understand human genetics by making DNA animal or a whole individual. Therefore, Dr. Ghaem- The investigators applied this validated ap- from everyone in a village at once. The data is all maghami’s team developed a new, 3D alternative. proach directly to infections of two major malaria jumbled up – what we really want is information Their test includes three types of human cells that species, Plasmodium falciparum, for which long from individuals. We are now able to look at malar- are typically in a person’s airway. In the body, these term culture is possible, and Plasmodium vivax, for ia infections with incredible detail. This will help cells are close together and are involved in the devel- which no long-term culture is feasible. They us understand how to best design drugs and vac- opment of respiratory conditions. The 3D model re- demonstrated that the single-cell genomics ap- cines to tackle this major global killer.” acted similar to an actual person’s airway when they proach could be used to generate parasite genome The study describing the novel single-cell ap- exposed it to allergens and bacterial extract. They say sequences directly from patient blood in order to proach for genome sequencing was published in that the model has the potential of reducing the need unravel the complexity of P. vivax and P. falciparum the May 8, 2014, online edition of the journal for some animal testing of new drugs for respiratory infections. Genome Research. conditions. Malaria parasite infections are complex and of- The study’s findings were published March 14, ten contain multiple different parasite genotypes Image: The malaria parasite invading a red blood cell 2014, in the ACS’ journal Molecular Pharmaceutics. and even different parasite species. “This has really (Photo courtesy of Shutterstock).

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AUTOMATED PURIFICATION SYSTEM CLINICAL CRYOSTAT SOFTWARE MODULE Shimadzu Scientific Instruments Thermo Fisher Scientific Titian Software The Crude2Pure automated purification/powder- The HM525 NX offers scientists improved func- The Mosaic Assay Requesting module is de- ization system eliminates time-consuming opera- tionality and ergonomics, ensuring efficient, high- signed to saving time, improve assay platform ef- tions, allowing researchers to focus on synthesiz- quality frozen sectioning. Key features include re- ficiency, and minimize waste of reagents and con- ing/isolating target compounds. The system is for liable and tested stepper motor technology that sumables. The new module offers a simple user use with preparative LC, and enables reliable delivers reproducible section thickness, and op- interface, and integrates fully with the existing Mo- large-scale, multi-sample processing. tional on-demand or scheduled UV disinfection. saic sample management software suite.

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Encapsulated Human-Insulin-Producing Progenitor Cells Cure Diabetes in Mouse Model breakthrough system that allows subcuta- molecules. The TheraCyte system is protected by AAneous implantation of encapsulated imma- 20 US patents and multiple foreign patent filings ture pancreatic cells (beta progenitor cells) was in Europe and Japan. shown to produce enough insulin to correct the The investigators monitored human insulin se- symptoms of diabetes in a mouse model. cretion and employed bioluminescent imaging to Investigators at the Sanford-Burnham Medical evaluate the maturation, growth, and contain- Research Institute (La Jolla, CA, USA; www. ment of the encapsulated islet progenitors. They sanfordburnham.org) and the University of Cali- reported in the March 24, 2014, online edition of fornia, San Diego (USA; www.ucsd.edu) placed the journal Stem Cell Research that human in- CyT49 pancreatic islets derived from human em- sulin was detectable by seven weeks post-trans- bryonic stem cells (hESCs) into TheraCyte (Lagu- plant and increased 17-fold over the course of na Hills, CA, USA; www.theracyte.com) encapsu- eight weeks, yet during this period the biomass of lation devices and transplanted the devices into a encapsulated cells remained constant. Remark- diabetic mouse model. ably, by 20 weeks post-transplant encapsulated The TheraCyte system for encapsulating and cells secreted sufficient levels of human insulin to transplanting cells is a thin membrane-bound ameliorate alloxan induced diabetes. Further- polymeric chamber. It is fabricated from biocom- more, bioluminescent imaging revealed that patible membranes, which protect allogeneic cells hESCs remained fully contained in the encapsula- from rejection by the recipient and, when im- tion device for up to 150 days, the longest period planted subcutaneously, induce the development tested. of blood capillaries close to the membranes. This vascularization feature provides a rich blood sup- Image: The TheraCyte system for encapsulating ply to nourish the tissues within the membranes, and transplanting cells is a thin membrane bound polymeric chamber. It is fabricated from biocompat- subcutaneously, induce the development of blood aids in the communication of implanted cells with ible membranes, which protect allogeneic cells capillaries close to the membranes (Photo courtesy the host, and assures rapid uptake of therapeutic from rejection by the recipient and, when implanted of TheraCyte). Vitamin D May Raise Survival Rates Among Cancer Patients ancer patients who have higher levels of vita- ceptor is present in nearly every cell in the body. dividual studies that measured vitamin D levels in CCmin D when they are diagnosed are inclined to “By reviewing studies that collectively examined cancer patients at the time of diagnosis and moni- have better survival rates and remain in remission vitamin D levels in 17,332 cancer patients, our tored survival rates. In most of the research, patients longer than patients who are vitamin D-deficient, analysis demonstrated that vitamin D levels are had their vitamin D levels tested before they under- according to new research. linked to better outcomes in several types of can- went any treatment for cancer. The study found a 10 The findings are scheduled for publication in the cer,” said one of the study’s authors, Hui Wang, nmol/L increase in vitamin D levels was tied to a 4% July 2014 issue of the Endocrine Society’s Journal MD, PhD, a professor of the Institute for Nutrition- increase in survival among cancer patients. of Clinical Endocrinology & Metabolism (JCEM). al Sciences at the Shanghai Institutes for Biological Researchers found the strongest association be- The body naturally produces vitamin D after expo- Sciences at the Chinese Academy of Sciences tween vitamin D levels and survival in breast can- sure to sunlight and absorbs it from specific foods. (Shanghai, China; http://sibs.cas.cn). “The results cer, lymphoma and colorectal cancer. There was Vitamin D affects a variety of biologic mechanisms suggest vitamin D may influence the prognosis for less evidence of a connection in people with Merkel by binding to a protein called a vitamin D receptor, people with breast cancer, colorectal cancer and cell carcinoma, lung cancer, gastric cancer, prostate in addition to helping the body absorb the calcium lymphoma, in particular.” cancer, leukemia, or melanoma but the available re- and phosphorus required for healthy bones. This re- The meta-analysis looked at the findings of 25 in- sults were positive.

Bio Research International July-August/2014 28 forto view latest this news issue updates in interactive visit www.BiotechDaily.com digital magazine format visit www.LinkXpress.com Bio Research International Chitosan Treatment Clears Way for Antibiotics To Eliminate Recurrent Urinary Tract Infections ecurrent urinary tract infection was success- eliminated. RRfully resolved in a mouse model by treat- “Effectively, there were no bacteria in the ment with the exfoliant chitosan followed by a bladder,” said Dr. Matthew Blango, a postdoc- round of antibiotics. toral researcher at the University of Utah. “An- Bacterial urinary tract infection (UTI), most tibiotics do not do a good job of getting rid of commonly caused by uropathogenic Escherichia reservoir populations, but when augmented coli (UPEC), can affect the kidneys, bladder, ure- with chitosan, there was a significant reduction tha or ureters. These bacteria usually are suscep- in the level of bacteria in mouse bladders.” tible to antibiotics, but they can to pass through the surface layer of cells lining the bladder and Image: Commercial chitosan is derived from the shells of shrimp and other sea crustaceans, includ- colonize deeper layers of cells and tissue where ing Pandalus borealis, pictured here (Photo cour- they lie dormant and are protected from destruc- tesy of Wikipedia). tion by antibiotics. These reservoirs are a potential source for the recurrent UTIs that affect millions of individuals annually. Investigators at the University of Utah (Salt Lake City, USA; www. utah.edu) used the exfoliant chitosan to remove the surface layer of bladder cells. Chitosan is a deacetylated derivative of chitin, which is the structural element in the exoskeleton of crustaceans (such as crabs and shrimp) and cell walls of fungi. It is being developed for a number of industrial, agricultural, and biomedical uses, including drug and vaccine delivery in animals and humans. A common method for the synthesis of chitosan is the deacetylation of chitin using sodium hydroxide in excess as a reagent and water as a solvent. On average, the molecular weight of commercially produced chitosan is between 3.8 and 20.0 kDa. The investigators found that when instilled for 20 minutes into the bladders of mice via catheterization, chitosan disrupted tight junctions and caused rapid exfoliation of the super- ficial epithelial cells without eliciting overt signs of inflammation. By inducing the exfoliation of the superfi- cial layers of the urothelium, chitosan stimulated rapid regenerative processes and induced the reactiva- tion of dormant intracellular UPEC populations. Upon removal of chitosan, the permeability barrier function of the urothelium was restored within several hours, and the tissue was completely regenerated within about a week. Working with a mouse model of recurrent UTI, the investigators followed up chitosan treatment by giving the animals a one-week course of fluoroquinolones, an antibiotic class commonly used to treat UTIs. They reported in the March 25, 2014, online edition of the journal PLOS ONE that examination of the mice one week after antibiotic treatment revealed that the reservoir UPEC populations had for the most part been

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Stem Cells Loaded with Oncolytic Herpes Virus Destroy Brain Tumors in Mouse Model ancer researchers treated resistant, and resected tumors. CCmouse models of the human TRAIL is a cytokine that is pro- brain tumor glioblastoma multi- duced and secreted by most normal forme by injecting the animals with tissue cells. It causes apoptosis pri- stem cells loaded with oncolytic her- marily in tumor cells by binding to pes virus and treated virus-resistant certain death receptors. Since the tumors with oncolytic herpes virus- mid-1990s it has been used as the es genetically engineered to express basis for several anticancer drugs, the proapoptotic cytokine TRAIL. but was not been found to have any Glioblastoma multiforme (GBM) significant survival benefit. is an aggressive brain tumor, fatal Results published in the June within one year from diagnosis in 2014 online edition of the Journal of most patients despite intensive treat- the [US] National Cancer Institute ment with surgery, radiation, and revealed that the MSC-oHSVs effec- chemotherapy. The migratory and tively produced oHSV progeny, microscopically invasive nature of which resulted in killing of GBMs in GBM as well as its resistance to vitro and in vivo mediated by a dy- chemotherapy renders conventional namic process of oHSV infection therapies inadequate in its treat- and tumor destruction. sECM-en- ment. Attempts to treat GMB with capsulated MSC-oHSVs resulted in oncolytic viruses have been unsuc- statistically significant increased an- cessful mainly because of insuffi- ti-GBM efficacy compared with di- cient viral spread after tumor resec- rect injection of purified oHSV in a glioblastoma patients undergo sur- jected the virus directly into the re- tion. preclinical model of GBM resection, gery for tumor debulking, and we section cavity did not follow the fate Investigators at Harvard Univer- resulting in prolonged median sur- have previously shown that MSCs of the virus in the cavity. However, sity (Cambridge, MA, USA; www. vival of the mice. In a model of virus encapsulated in biocompatible gels our imaging and side-by-side com- harvard.edu) loaded human mes- resistant tumors, it was seen that can be used as therapeutic agents in parison studies showed that the enchymal stem cells (MSC) with on- MSCs loaded with oHSV-TRAIL ef- a mouse model that mimics this de- naked virus rarely infects the resid- colytic herpes simplex virus (MSC- fectively induced apoptosis-mediat- bulking. So, we loaded MSCs with ual tumor cells. This could give us oHSV), and the fate of the stem cells ed killing and prolonged median sur- oncolytic herpes virus and encapsu- insight into why the results from following injection into mice was vival of the mice. lated these cells in biocompatible clinical trials with oncolytic viruses followed by real-time imaging in vit- “Our approach can overcome gels and applied the gels directly on- alone were modest.” ro and in vivo. The efficacy of MSC- problems associated with current to the adjacent tissue after debulk- oHSV and its proapoptotic variant, clinical procedures,” said senior au- ing. We then compared the efficacy Image: The oncolytic herpes simplex virus (oHSV) appeared to have so oHSV-TRAIL (tumor necrosis factor- thor Dr. Khalid Shah, professor of of virus-loaded, encapsulated MSCs much potential against malignant related apoptosis-inducing ligand) medicine at Harvard University. versus direct injection of the virus glioblastoma multiforme, the most encapsulated in synthetic extracellu- “The work will have direct implica- into the cavity of the debulked tu- common brain tumor in human adults, lar matrix (sECM), was tested in dif- tions for designing clinical trials us- mors. They survived because the that researchers looked for a way to increase its staying power (Photo ferent mouse GBM models, which ing oncolytic viruses, not only for virus does not get washed out by courtesy of Khalid Shah, Ph.D., Har- more accurately reflected the cur- brain tumors, but for other solid tu- the cerebrospinal fluid that fills the vard University / Sebastian Kaulitzki, rent clinical settings of malignant, mors. We know that 70%–75% of cavity. Previous studies that have in- Fotolia).

Bio Research International July-August/2014 30 to view this issue in interactive digital magazine format visit www.LinkXpress.com Bio Research International 3D Printed Cancer Cells Mimic Tumors group of Chinese and American researchers cancer drugs. AAhave successfully created a three-dimension- The lead author of the research, Prof. Wei Sun, al (3D) model of a cancerous tumor using a 3D from Tsinghua University (Beijing, China; www. printer. The model, which consists of a scaffold of tsinghua.edu.cn), and Drexel University (Phi- fibrous proteins coated in cervical cancer cells, ladelphia, PA, USA; www.drexel.edu), said, “We has provided an accurate 3D representation of a have provided a scalable and versatile 3D cancer tumor’s environment and could help in the dis- model that shows a greater resemblance to natu- covery of new drugs and cast new light on how ral cancer than 2D cultured cancer cells. With fur- tumors develop, grow, and metastasize through- ther understanding of these 3D models, we can out the body. use them to study the development, invasion, The study’s findings were published April 11, metastasis and treatment of cancer using specific 2014, in the Institute of Physics (IOP) Publishing’s cancer cells from patients. We can also use these journal Biofabrication. The model consists of a grid models to test the efficacy and safety of new can- Image: The 3-D tumor cellular morphology on day 8 structure, 10 mm in width and length, composed cer treatment therapies and new cancer drugs.” of testing (Photo courtesy of the Institute of Physics). of gelatin, alginate, and fibrin, which recreates the fibrous proteins that make up the extracellular matrix of a tumor. The grid structure is coated in Hela cells – an unusual, “immortal” cell line that was first derived from a cervical cancer patient in 1951. Because the cells’ ability to divide forever in a laboratory setting, the cell line has been used in some of the most substantial scientific studies of the past 50 years. WORLD’S MEDICAL DEVICE MARKETPLACE Although the most effective approach to studying tumors is to do so SIGN UP in a clinical trial, ethical and safety re- FOR FREE! strictions make it hard for these types of studies to be performed on a wide scale. To overcome this, 2D models, consisting of a single layer of cells, have been created to mimic the physi- ologic environment of tumors so that different types of drugs can be evaluated in a realistic manner. With the dawn of 3D printing, it is now possible to provide a more realistic representation of the environment surrounding a tumor, which the researchers have demonstrated in this study by comparing results from their 3D model with results from a 2D model. In addition to assessing if the cells remained viable (alive) after printing, the researchers also examined how the cells proliferated, how they expressed a specific set of proteins, and how resistant they were to anticancer agents. The proteins examined were part of the matrix metalloproteinases (MMP) protein family. These proteins are used by cancer cells to break Connecting Buyers with through their surrounding matrix and Suppliers Worldwide help tumors to spread. Resistance to anticancer drugs, which was also Reach new sources of supply studied, is a good indicator of tumor Identify latest products and technologies malignancy. Send inquiries directly to suppliers The findings revealed that 90% of Receive latest product alerts the cancer cells remained viable after Chat live with suppliers the printing process. The findings also demonstrated that the 3D model had TradeMed provides a sophisticated yet easy-to-use global B2B platform for sourcing medical more similar characteristics to a tumor equipment. TradeMed connects buyers and sellers worldwide through a safe, secure and dy- compared to 2D models and in the 3D namic network. Solely dedicated to medical products, TradeMed is the premier choice for med- model the cancer cells showed a high- ical suppliers, hospital decisionmakers and buyers worldwide, regardless of size or budget. er proliferation rate, higher protein expression and higher resistance to anti-

Bio Research International 31 July-August/2014 Bio Research International for latest news updates visit www.BiotechDaily.com Epigenomic Mapping Highlights Differences Between Ancient and Modern Humans olecular biologists employing advanced epi- Germany; www.eva.mpg.de) reconstructed the MMgenetic techniques have identified genetic full DNA methylation maps of the Neandertal and differences between Homo sapiens and extinct the Denisovan by harnessing the natural degrada- types of humans such as Neanderthals and Deniso- tion processes of methylated and unmethylated cy- vans that are linked to modern diseases like tosines. Alzheimer’s disease, autism, and schizophrenia. The investigators reported in the April 17, Epigenomics is the study of the complete set of 2014, online edition of the journal Science that by epigenetic modifications on the genetic material of comparing these ancient methylation maps to a cell, known as the epigenome. The field is anal- those of present-day humans, they had identified ogous to genomics and proteomics, which are the nearly 2000 differentially methylated regions study of the genome and proteome of a cell. Epige- (DMRs). Particularly, they found substantial netic modifications are reversible modifications to methylation changes in the HOXD cluster that a cell’s DNA or histones that affect gene expression may explain anatomical differences between ar- without altering the DNA sequence. Two of the chaic and present-day humans. Hox genes (from most characterized epigenetic modifications are an abbreviation of homeobox) are a group of relat- DNA methylation and histone modification. Epige- ed genes that control the body plan of the embryo netic modifications play an important role in gene along the anterior-posterior axis. After the embry- expression and regulation, and are involved in nu- onic segments have formed, the Hox proteins de- merous cellular processes such as in differentia- termine the type of segment structures (e.g., legs, tion/development and tumorigenesis. Recent ad- antennae, and wings in fruit flies or the different provides insight into the epigenetic landscape of vances in high-throughput analytical technology types of vertebrae in humans) that will form on a our closest evolutionary relatives and opens a win- have enabled rapid advances in epigenomic re- given segment. dow to explore the epigenomes of extinct search. Additionally, the investigators found that DMRs species.” The evolution of epigenetic regulation along were significantly more likely to be associated with the human lineage remains largely unexplored. To modern diseases such as Alzheimer’s disease, Image: Working in a clean room, researchers took shed further light on this topic, investigators at the autism and schizophrenia, suggesting that recent extensive precautions to avoid contaminating Nean- Hebrew University of Jerusalem (Israel; www. epigenetic changes in brain tissues may underlie derthal DNA samples - extracted from bones like this one - with DNA from any other source, including mod- huji.ac.il) and their colleagues at the Max Planck some of today’s common psychiatric disorders. ern humans (Photo courtesy of the Max Planck Insti- Institute for Evolutionary Anthropology (Leipzig, The authors concluded by saying, “This study tute for Evolutionary Anthropology). Actin-Binding Surface on Vinculin Mediates Mechanical Aspects of Cell Movement

team of cell biologists has obtained data that Image: Proteins actin and vinculin bind together at a site iden- AAshows how two proteins, vinculin and actin, tified by researchers at the University of North Carolina. The function in concert to regulate cell morphology, interaction of the proteins plays an important role in cell motility, and mechanotransduction (the conversion movement (Photo courtesy of the UNC / Campbell Lab). of mechanical signals into electrical or chemical signals) and play a critical role in metastasis. Vinculin is a cytoskeletal scaffold protein essential for embryogenesis and cardiovascular function. It localizes to focal adhesions and adherens junctions, where it connects cell surface receptors to the actin cytoskeleton. While vinculin interacts with many adhesion proteins, its interaction with filamentous actin regulates cell morphology, motility, and mechanotransduction. Investigators at the University of North Carolina (Chapel Hill, USA; www.unc.edu) used negative- stain electron microscopy, discrete molecular dynamics techniques, and mutagenesis to develop a new model to explain the interaction between vinculin and actin. A major breakthrough in this effort of this interaction, including actin-induced confor- tions. If you disrupt that, the hypothesis is that cells was the development of mutated versions of vin- mational changes that promoted actin bundling. no longer respond appropriately to force and the or- culin that disrupted the actin/vinculin interaction “Our data suggest that there is a face on the vin- gan suffers.” in specific and traceable fashion. culin tail that has been ignored by the previous “Our data supported a unique surface that was Results published in the April 2014 online edi- model, and that it is very important,” said first au- important for actin binding,” said senior author Dr. tion of the journal Structure revealed that actin- thor Peter Thompson, a graduate researcher at the Sharon Campbell, professor of biochemistry and binding deficient vinculin variants expressed in vin- University of North Carolina. “In your cardiovascu- biophysics at the University of North Carolina. culin knockout fibroblasts failed to correct cell- lar system – your heart and arteries – the cells that “Identification of this actin binding surface on vin- spreading defects and reduced cellular response to form these organs need to stick together tightly. culin has enabled us to dissect how this critical in- external force. These findings highlighted the im- They do these in part by forming cell-to-cell ad- teraction controls how cells respond to force and portance of this actin-binding surface and provided herens junctions. Vinculin creates a critical physical move. This in turn, will help us better understand the molecular basis for elucidating additional roles link between the actin cytoskeleton and these junc- how dysregulation leads to disease.”

Bio Research International July-August/2014 32 to view this issue in interactive digital magazine format visit www.LinkXpress.com INDUSTRY NEWS Cancer Immunotherapy Sector to Surge to Teva Acquisition to Expand USD 9 Billion Across Major Pharma Through 2022 Pain Care Offerings he immunotherapy market will Group (Burlington, MA, USA; www. eva Pharmaceutical Industries, cy episodic and chronic migraine TTexperience substantial growth decisionresources.com). Combined, TTLtd. (Petach Tikva, Israel; www. complements the recent addition of through 2022, increasing from USD Bristol-Myers Squibb’s anti-CTLA-4 tevapharm.com) will acquire Labrys Zecuity, an innovative therapy for 1.1 billion in 2012 to nearly USD 9 agent Yervoy and innovative immune Biologics, Inc. (San Mateo, CA, USA; the acute treatment of migraine, ob- billion in 2022 (corresponding to checkpoint inhibitors that target the www.labrysbiologics.com). The ac- tained through the acquisition of 23.8% annual growth) in the United anti-programmed cell death-1/pro- quisition will broaden Teva’s array of NuPathe. Kingdom, United States, France, Ger- grammed death-ligand-1 (PD-1/PD- biotechnology assets and capabilities. This ability to treat both acute and many, Italy, Spain, and Japan, accord- L1) pathway – including Bristol-My- Teva will purchase Labrys for USD chronic migraine builds on Teva’s ing to recent market research. ers Squibb/Ono Pharmaceutical’s 200 million in upfront payment in broader pain portfolio, which was re- This notable growth will be fueled nivolumab, Merck & Co.'s pem- cash at closing as well as up to USD cently further strengthened by posi- by the anticipated market entry of brolizumab (MK-3475), Roche/ 625 million in contingent payments tive phase III results achieved by Te- nine novel immunotherapies--includ- Genentech/Chugai’s MPDL-3280A upon achievement of certain pre- va’s potential abuse-deterrent extend- ing four novel immune checkpoint and AstraZeneca/MedImmune’s ME- launch milestones. Potential peak ed release hydrocodone. The results inhibitors and five novel therapeutic DI4736 – should dominate the im- sales for LBR-101 are estimated to gave a clear indication, in a clinical vaccines – in new oncology indica- munotherapy market and capture a reach USD 2–3 billion. With the goal setting, of the promise of Teva’s pro- tions and/or patient populations, remarkable 85% market share in of becoming a global leader in pain by prietary technology with potential according to Decision Resources 2022. 2020, the Labrys acquisition adds a abuse-deterrent properties in a range significant migraine prophylaxis di- of opioid medications. mension to Teva’s extensive pain care “Teva is the ideal company to con- Abbott Selling Developed franchise, which includes a range of tinue Labrys’ efforts to rapidly ad- investigational, approved, and mar- vance the LBR-101 program and Market Generics Portfolio keted treatments for migraine, cancer bring a much needed product to mar- bbott Laboratories (Abbot Park, quired on a debt-free basis, include a pain, and chronic pain. ket,” said Steven P. James, Labrys’ AAIL, USA; www.abbott.com) has portfolio of more than 100 specialty Labrys is developing LBR-101, a president and chief executive officer. sold its developed market generic and branded generic pharmaceutical fully humanized monoclonal anti- “Since closing a Series A investment drugs business to Mylan (Canons- products in five major therapeutic ar- body that binds to calcitonin gene- round in 2013, Labrys has made re- burg, PA, USA; www.mylan.com) in eas – central nervous system/pain, related peptide (CGRP) currently in markable strides advancing LBR-101 a deal worth USD 5.3 billion. cardio/metabolic, gastrointestinal, an- phase IIb clinical trials for preven- in a robust phase 2 development pro- The sale to Mylan will be in the ti-infective/respiratory, and women's tion of chronic and episodic mi- gram and attracting a high caliber form of an equity ownership of a and men's health – and also includes graine. Teva’s acquisition of the LBR- company in Teva to complete clinical newly formed entity, to be named several patent protected, novel, and 101 program targeting high frequen- development.” Mylan NV, in which Abbott will have hard-to-manufacture products with a stake of 21%. The new entity will continued growth potential. be based in the Netherlands to Abbott will retain its branded achieve tax savings. Mylan NV will generics pharmaceuticals business combine Mylan's existing business and products in emerging markets, and Abbott's developed markets where demographics and growing pharmaceuticals business, which in- healthcare systems are combining to cludes Europe, Japan, Canada, Aus- create an increased rate of patient ac- tralia, and New Zealand, as well as cess to healthcare, and where the manufacturing facilities in France and majority of healthcare products are Japan. The transaction will diversify paid for directly by the consumer. Ab- Mylan's business and strengthen its bott will also retain manufacturing fa- commercial platform outside the US cilities in emerging markets as well as (the US sector is not included). those situated in the Netherlands, The assets, which are being ac- Germany, and Canada.

IDT Acquires Nuclease Product Line he Surveyor line is to be used by clinical and research services. As part TTIntegrated DNA Technologies of the agreement, IDT will acquire (IDT; Coralville, IA, USA; www. the Surveyor product line and intel- idtdna.com) primarily to support re- lectual property. Transgenomic will searchers performing mutation detec- receive an exclusive license for clini- tion and potentially-clinical genome cal and diagnostic use of Surveyor editing, and by Transgenomic, products from IDT. Additional terms Inc. (Omaha, NE, USA; www.trans of the acquisition were not disclosed. genomic.com) primarily to support The key component of Surveyor diagnostic and other clinical applica- products is Surveyor Nuclease, a tions. member of the CEL nuclease family IDT, a world leader in custom nu- of mismatch-specific nucleases isolat- cleic acid synthesis, is expanding its ed from celery. Surveyor Nuclease offerings by adding the Surveyor en- has been shown to recognize and zyme and kits of Transgenomic, a cleave mismatches arising from single global company advancing diagnos- nucleotide polymorphisms or small tics, cytogenetics, and specialized insertions or deletions.

Bio Research International 33 July-August/2014 INTERNATIONAL CALENDAR

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