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WO 2018/064165 A2 (.Pdf)
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/064165 A2 05 April 2018 (05.04.2018) W !P O PCT (51) International Patent Classification: Published: A61K 35/74 (20 15.0 1) C12N 1/21 (2006 .01) — without international search report and to be republished (21) International Application Number: upon receipt of that report (Rule 48.2(g)) PCT/US2017/053717 — with sequence listing part of description (Rule 5.2(a)) (22) International Filing Date: 27 September 2017 (27.09.2017) (25) Filing Language: English (26) Publication Langi English (30) Priority Data: 62/400,372 27 September 2016 (27.09.2016) US 62/508,885 19 May 2017 (19.05.2017) US 62/557,566 12 September 2017 (12.09.2017) US (71) Applicant: BOARD OF REGENTS, THE UNIVERSI¬ TY OF TEXAS SYSTEM [US/US]; 210 West 7th St., Austin, TX 78701 (US). (72) Inventors: WARGO, Jennifer; 1814 Bissonnet St., Hous ton, TX 77005 (US). GOPALAKRISHNAN, Vanch- eswaran; 7900 Cambridge, Apt. 10-lb, Houston, TX 77054 (US). (74) Agent: BYRD, Marshall, P.; Parker Highlander PLLC, 1120 S. Capital Of Texas Highway, Bldg. One, Suite 200, Austin, TX 78746 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. -
Arxiv:2105.11503V2 [Physics.Bio-Ph] 26 May 2021 3.1 Geometry and Swimming Speeds of the Cells
The Bank Of Swimming Organisms at the Micron Scale (BOSO-Micro) Marcos F. Velho Rodrigues1, Maciej Lisicki2, Eric Lauga1,* 1 Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA, United Kingdom. 2 Faculty of Physics, University of Warsaw, Warsaw, Poland. *Email: [email protected] Abstract Unicellular microscopic organisms living in aqueous environments outnumber all other creatures on Earth. A large proportion of them are able to self-propel in fluids with a vast diversity of swimming gaits and motility patterns. In this paper we present a biophysical survey of the available experimental data produced to date on the characteristics of motile behaviour in unicellular microswimmers. We assemble from the available literature empirical data on the motility of four broad categories of organisms: bacteria (and archaea), flagellated eukaryotes, spermatozoa and ciliates. Whenever possible, we gather the following biological, morphological, kinematic and dynamical parameters: species, geometry and size of the organisms, swimming speeds, actuation frequencies, actuation amplitudes, number of flagella and properties of the surrounding fluid. We then organise the data using the established fluid mechanics principles for propulsion at low Reynolds number. Specifically, we use theoretical biophysical models for the locomotion of cells within the same taxonomic groups of organisms as a means of rationalising the raw material we have assembled, while demonstrating the variability for organisms of different species within the same group. The material gathered in our work is an attempt to summarise the available experimental data in the field, providing a convenient and practical reference point for future studies. Contents 1 Introduction 2 2 Methods 4 2.1 Propulsion at low Reynolds number . -
Bioflocculation of Wastewater Organic Matter at Short Retention Times
Bioflocculation of Wastewater Organic Matter at Short Retention Times Lena Faust Thesis committee Promotor Prof. dr. ir. H.H.M. Rijnaarts Professor, Chair Environmental Technology Wageningen University Co-promotor Dr. ir. H. Temmink Assistant professor, Sub-department of Environmental Technology Wageningen University Other members Prof. Dr A.J.M. Stams, Wageningen University Prof. Dr. I. Smets, University of Leuven, Belgium Prof. Dr. B.-M. Wilen, Chalmers University of Technology, Sweden Prof. Dr. D.C. Nijmeijer, University of Twente, The Netherlands This research was conducted under the auspices of the Graduate School SENSE (Socio- Economic and Natural Sciences of the Environment) Bioflocculation of Wastewater Organic Matter at Short Retention Times Lena Faust Thesis submitted in fulfillment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. Dr M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Wednesday 3rd of December 2014 at 1.30 p.m. in the Aula. Lena Faust Bioflocculation of Wastewater Organic Matter at Short Retention Times, 163 pages. PhD thesis, Wageningen University, Wageningen, NL (2014) With references, with summaries in English and Dutch ISBN 978-94-6257-171-6 ˮDa steh ich nun, ich armer Tor, und bin so klug als wie zuvor.ˮ Dr. Faust (in Faust I written by Johann Wolgang von Goethe) Contents 1 GENERAL INTRODUCTION ....................................................................................................................1 -
Import of an Extinct Disease?
OBSERVATION Pinta in Austria (or Cuba?) Import of an Extinct Disease? Ingrid Woltsche-Kahr, MD; Bruno Schmidt, PhD; Werner Aberer, MD; Elisabeth Aberer, MD Background: Pinta, 1 of the 3 nonvenereal treponema- detection of spirochetes in the trunk lesion indicated early toses, is supposed to be extinct in most areas in South and secondary syphilis, but an extensive case history and the Central America, where it was once endemic. Only scat- clinical appearance fulfilled all criteria for pinta. tered foci may still remain in remote areas in the Brazilian rain forest, and the last case from Cuba was reported in 1975. Conclusion: The acquisition of a distinct clinical en- tity, pinta, in a country where it was formerly endemic Observation: A native Austrian woman, who had lived but now is believed to be extinct raises the question of for 7 years in Cuba and was married to a Cuban native, whether the disease is in fact extinct or whether syphilis developed a singular psoriasiform plaque on her trunk and pinta are so similar that no definite distinction is pos- and several brownish papulosquamous lesions on her sible in certain cases. palms and soles during a visit to her home in Austria. Positive serological findings for active syphilis and the Arch Dermatol. 1999;135:685-688 HE NONVENEREAL trepone- after the appearance of pintids), lesions matoses yaws, endemic marked by vitiligolike depigmentation are syphilis (bejel), and pinta the leading feature. These lesions are not are caused by an organism believed to be infectious. Histopathologi- that is morphologically and cal investigations show moderate acan- Tantigenically identical to the causative agent thosis, spongiosis, sometimes hyperkera- of venereal syphilis, Treponema pallidum. -
The Isolation of Novel Lachnospiraceae Strains and the Evaluation of Their Potential Roles in Colonization Resistance Against Clostridium Difficile
The isolation of novel Lachnospiraceae strains and the evaluation of their potential roles in colonization resistance against Clostridium difficile Diane Yuan Wang Honors Thesis in Biology Department of Ecology and Evolutionary Biology College of Literature, Science, & the Arts University of Michigan, Ann Arbor April 1st, 2014 Sponsor: Vincent B. Young, M.D., Ph.D. Associate Professor of Internal Medicine Associate Professor of Microbiology and Immunology Medical School Co-Sponsor: Aaron A. King, Ph.D. Associate Professor of Ecology & Evolutionary Associate Professor of Mathematics College of Literature, Science, & the Arts Reader: Blaise R. Boles, Ph.D. Assistant Professor of Molecular, Cellular and Developmental Biology College of Literature, Science, & the Arts 1 Table of Contents Abstract 3 Introduction 4 Clostridium difficile 4 Colonization Resistance 5 Lachnospiraceae 6 Objectives 7 Materials & Methods 9 Sample Collection 9 Bacterial Isolation and Selective Growth Conditions 9 Design of Lachnospiraceae 16S rRNA-encoding gene primers 9 DNA extraction and 16S ribosomal rRNA-encoding gene sequencing 10 Phylogenetic analyses 11 Direct inhibition 11 Bile salt hydrolase (BSH) detection 12 PCR assay for bile acid 7α-dehydroxylase detection 12 Tables & Figures Table 1 13 Table 2 15 Table 3 21 Table 4 25 Figure 1 16 Figure 2 19 Figure 3 20 Figure 4 24 Figure 5 26 Results 14 Isolation of novel Lachnospiraceae strains 14 Direct inhibition 17 Bile acid physiology 22 Discussion 27 Acknowledgments 33 References 34 2 Abstract Background: Antibiotic disruption of the gastrointestinal tract’s indigenous microbiota can lead to one of the most common nosocomial infections, Clostridium difficile, which has an annual cost exceeding $4.8 billion dollars. -
Molecular Studies of Treponema Pallidum
Fall 08 Molecular Studies of Treponema pallidum Craig Tipple Imperial College London Department of Medicine Section of Infectious Diseases Thesis submitted in fulfillment of the requirements for the degree of Doctor of Philosophy of Imperial College London 2013 1 Abstract Syphilis, caused by Treponema pallidum (T. pallidum), has re-emerged in the UK and globally. There are 11 million new cases annually. The WHO stated the urgent need for single-dose oral treatments for syphilis to replace penicillin injections. Azithromycin showed initial promise, but macrolide resistance-associated mutations are emerging. Response to treatment is monitored by serological assays that can take months to indicate treatment success, thus a new test for identifying treatment failure rapidly in future clinical trials is required. Molecular studies are key in syphilis research, as T. pallidum cannot be sustained in culture. The work presented in this thesis aimed to design and validate both a qPCR and a RT- qPCR to quantify T. pallidum in clinical samples and use these assays to characterise treatment responses to standard therapy by determining the rate of T. pallidum clearance from blood and ulcer exudates. Finally, using samples from three cross-sectional studies, it aimed to establish the prevalence of T. pallidum strains, including those with macrolide resistance in London and Colombo, Sri Lanka. The sensitivity of T. pallidum detection in ulcers was significantly higher than in blood samples, the likely result of higher bacterial loads in ulcers. RNA detection during primary and latent disease was more sensitive than DNA and higher RNA quantities were detected at all stages. Bacteraemic patients most often had secondary disease and HIV-1 infected patients had higher bacterial loads in primary chancres. -
Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner
microorganisms Article Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner Bokyoung Lee 1,2, Jieun Lee 1,2, Min-Yeong Woo 1,2, Mi Jin Lee 1, Ho-Joon Shin 1,2, Kyongmin Kim 1,2 and Sun Park 1,2,* 1 Department of Microbiology, Ajou University School of Medicine, Youngtongku Wonchondong San 5, Suwon 442-749, Korea; [email protected] (B.L.); [email protected] (J.L.); [email protected] (M.-Y.W.); [email protected] (M.J.L.); [email protected] (H.-J.S.); [email protected] (K.K.) 2 Department of Biomedical Sciences, The Graduate School, Ajou University, Youngtongku Wonchondong San 5, Suwon 442-749, Korea * Correspondence: [email protected]; Tel.: +82-31-219-5070 Received: 22 August 2020; Accepted: 9 September 2020; Published: 11 September 2020 Abstract: T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) is an immune checkpoint molecule and a target for anti-cancer therapy. In this study, we examined whether gut microbiota manipulation altered the anti-tumour efficacy of Tim-3 blockade. The gut microbiota of mice was manipulated through the administration of antibiotics and oral gavage of bacteria. Alterations in the gut microbiome were analysed by 16S rRNA gene sequencing. Gut dysbiosis triggered by antibiotics attenuated the anti-tumour efficacy of Tim-3 blockade in both C57BL/6 and BALB/c mice. Anti-tumour efficacy was restored following oral gavage of faecal bacteria even as antibiotic administration continued. In the case of oral gavage of Enterococcus hirae or Lactobacillus johnsonii, transferred bacterial species and host mouse strain were critical determinants of the anti-tumour efficacy of Tim-3 blockade. -
Syphilis Onset Seizures, a Head CT Reveals an Acute CVA • 85 Yo Woman C/O Shooting Pains Down Her Simon J
• 43 yo woman with RUQ pain is found to have a liver mass on U/S, biopsy of the mass reveals granulomas • 26 yo man presents to the ED with new- Syphilis onset seizures, a Head CT reveals an acute CVA • 85 yo woman c/o shooting pains down her Simon J. Tsiouris, MD, MPH Assistant Professor of Clinical Medicine and Clinical Epidemiology arms and in her face for 2 years duration Division of Infectious Diseases College of Physicians and Surgeons • 36 yo man presents to his PMD with an Columbia University enlarging lymph node in his neck 55 yo man presents to the ER with chest pain radiating to his back, 19 yo man is seen at an STD clinic shortness of breath and is found to have this on Chest CT for a painless ulcer on his penis Aortic aneurysm rupture. Axial postcontrast image through the aortic arch reveals an aortic aneurysm with contrast penetrating the thrombus within the aneurysm (open arrow). Note the high attenuation material within the mediastinal fat (arrowheads), representing blood and indicating the presence of aneurysm rupture. 26 yo man presents to an ophthalmologist with progressive loss of vision in his Left eye, his fundoscopic exam looks like the picture on the left: Mercutio: “… a pox on your houses!” Romeo and Juliet, 1st Quarto, 1597, William Shakespeare Normal MID 15 Famous people who (probably) had syphilis • Ivan the Terrible • Henry VIII •Cortes • Francis I • Charles Baudelaire • Meriwether Lewis • Friedrich Nietzche • Gaetano Donizetti • Toulouse Lautrec • Al Capone Old World disease which always existed and happened •… New NewWorld World agent disease which mutatedwhich was and transmitted created a newto the Old Old World World? disease? to flare up around the time of New World exploration? The Great Pox – Origins of syphilis Syphilis in the 1500s • Pre-Colombian New World skeletal remains have bony lesions consistent with syphilis • T. -
Genetic Diversity in Treponema Pallidum: Implications for Pathogenesis, Evolution and Molecular Diagnostics of Syphilis and Yaws ⇑ David Šmajs A, , Steven J
Infection, Genetics and Evolution 12 (2012) 191–202 Contents lists available at SciVerse ScienceDirect Infection, Genetics and Evolution journal homepage: www.elsevier.com/locate/meegid Review Genetic diversity in Treponema pallidum: Implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws ⇑ David Šmajs a, , Steven J. Norris b, George M. Weinstock c a Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, Building A6, 625 00 Brno, Czech Republic b Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA c The Genome Institute, Washington University, 4444 Forest Park Avenue, Campus Box 8501, St. Louis, MO 63108, USA article info abstract Article history: Pathogenic uncultivable treponemes, similar to syphilis-causing Treponema pallidum subspecies pallidum, Received 21 September 2011 include T. pallidum ssp. pertenue, T. pallidum ssp. endemicum and Treponema carateum, which cause yaws, Received in revised form 5 December 2011 bejel and pinta, respectively. Genetic analyses of these pathogens revealed striking similarity among Accepted 7 December 2011 these bacteria and also a high degree of similarity to the rabbit pathogen, Treponema paraluiscuniculi,a Available online 15 December 2011 treponeme not infectious to humans. Genome comparisons between pallidum and non-pallidum trepo- nemes revealed genes with potential involvement in human infectivity, whereas comparisons between Keywords: pallidum and pertenue treponemes identified genes possibly involved in the high invasivity of syphilis Treponema pallidum treponemes. Genetic variability within syphilis strains is considered as the basis of syphilis molecular Treponema pallidum ssp. pertenue Treponema pallidum ssp. endemicum epidemiology with potential to detect more virulent strains, whereas genetic variability within a single Treponema paraluiscuniculi strain is related to its ability to elude the immune system of the host. -
( 12 ) United States Patent
US009956282B2 (12 ) United States Patent ( 10 ) Patent No. : US 9 ,956 , 282 B2 Cook et al. (45 ) Date of Patent: May 1 , 2018 ( 54 ) BACTERIAL COMPOSITIONS AND (58 ) Field of Classification Search METHODS OF USE THEREOF FOR None TREATMENT OF IMMUNE SYSTEM See application file for complete search history . DISORDERS ( 56 ) References Cited (71 ) Applicant : Seres Therapeutics , Inc. , Cambridge , U . S . PATENT DOCUMENTS MA (US ) 3 ,009 , 864 A 11 / 1961 Gordon - Aldterton et al . 3 , 228 , 838 A 1 / 1966 Rinfret (72 ) Inventors : David N . Cook , Brooklyn , NY (US ) ; 3 ,608 ,030 A 11/ 1971 Grant David Arthur Berry , Brookline, MA 4 ,077 , 227 A 3 / 1978 Larson 4 ,205 , 132 A 5 / 1980 Sandine (US ) ; Geoffrey von Maltzahn , Boston , 4 ,655 , 047 A 4 / 1987 Temple MA (US ) ; Matthew R . Henn , 4 ,689 ,226 A 8 / 1987 Nurmi Somerville , MA (US ) ; Han Zhang , 4 ,839 , 281 A 6 / 1989 Gorbach et al. Oakton , VA (US ); Brian Goodman , 5 , 196 , 205 A 3 / 1993 Borody 5 , 425 , 951 A 6 / 1995 Goodrich Boston , MA (US ) 5 ,436 , 002 A 7 / 1995 Payne 5 ,443 , 826 A 8 / 1995 Borody ( 73 ) Assignee : Seres Therapeutics , Inc. , Cambridge , 5 ,599 ,795 A 2 / 1997 McCann 5 . 648 , 206 A 7 / 1997 Goodrich MA (US ) 5 , 951 , 977 A 9 / 1999 Nisbet et al. 5 , 965 , 128 A 10 / 1999 Doyle et al. ( * ) Notice : Subject to any disclaimer , the term of this 6 ,589 , 771 B1 7 /2003 Marshall patent is extended or adjusted under 35 6 , 645 , 530 B1 . 11 /2003 Borody U . -
The Effect of Inoculum on the Performance of Sulfatereducing
ARTICLE IN PRESS WATER RESEARCH 41 (2007) 904– 914 Available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/watres The effect of inoculum on the performance of sulfate- reducing columns treating heavy metal contaminated water A. Prudena, N. Messnerb, L. Pereyraa, R.E. Hansona, S.R. Hiibelb, K.F. Reardonb,Ã aDepartment of Civil and Environmental Engineering, Colorado State University, Fort Collins, CO 80523, USA bDepartment of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA article info abstract Article history: Sulfate-reducing permeable reactive zones (SR-PRZs) are a passive means of immobilizing Received 27 April 2006 metals and neutralizing the pH of mine drainage through microbially mediated reactions. Received in revised form In this bench-scale study, the influence of inoculum on the performance of columns 8 November 2006 simulating SR-PRZs was investigated using chemical and biomolecular analyses. Columns Accepted 10 November 2006 inoculated from two sources (bovine dairy manure (DM) and a previous sulfate-reducing Available online 12 January 2007 column (SRC)) and uninoculated columns (U) were fed a simulated mine drainage and Keywords: compared on the basis of pH neutralization and removal of cadmium, zinc, iron, and Mine drainage treatment sulfate. Cadmium, zinc, and sulfate removal was significantly higher in SRC columns than Sulfate-reducing bacteria in the DM and U columns, while there was no significant difference between the DM and U Microbial ecology columns. Denaturing gradient gel electrophoresis (DGGE) analysis revealed differences in Molecular biology the microbial community composition among columns with different inocula, and Environmental biotechnology indicated that the microbial community in the SRC columns was the first to reach a pseudo-steady state.