DOCSLIB.ORG

How Does Variation Count? Using Improved Molecular Technology, Particularly the Ready Amplification of Alice S

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
How Does Variation Count? Using Improved Molecular Technology, Particularly the Ready Amplification of Alice S NEWS AND VIEWS VIROLOGY---------------- (M, Nowak, University of Oxford). How does variation count? Using improved molecular technology, particularly the ready amplification of Alice S. Huang and John M. Coffin nucleic acid sequences by the polymerase chain reaction, mutational WHAT do virologists, evolutionary could account for altered virulence in the heterogeneity is easily detected among biologists, population geneticists, mathe­ infected host. Sparked by what seems to different specimens taken at the same matical modellers, epidemiologists and be a remarkable genetic plasticity among time and place from different patients, physicians have in common? At a recent human immunodeficiency virus and the and in sequential specimens taken from EMBO workshop* an area of overlap annual emergence of threatening new the same patient. Although genetic emerged that could grow into a powerful influenza virus strains, a closer inspec­ variation may itself be important for scientific interface. New approaches tion was made of what is currently pathogenesis, the immune system pro­ were reported for analysing viral disease known about mutation rates for viruses. vides an important selective force (R. processes and evolutionary relationships, Rates of mutation for RNA genomes are Zinkernagel. University of Zurich; R, in which computer simulations were com­ now estimated to be 1,OOO-fold higher Phillips, John Radcliffe Hospital, Ox­ bined with the wealth of molecular data than for DNA genomes (J. Drake, ford; S. Carpenter. Iowa State Universi­ being generated by the sequencing of National Institute of Environmental ty; A. Leigh-Brown, University of Edin­ viral genomes. Complex but manipulat­ Health Sciences), Furthermore, the rates burgh). Disappointingly. there were no able experimental viral systems were are highly variable from site to site in the clear-cut correlations between the de­ used to test theories of population dy­ same genome (T. Kunkel, National gree of heterogeneity and the course of namics. And, almost as an aside, it was Institute of Environmental Health disease, It may well be that genetic firmly established that all RNA viruses, Sciences; B. Preston, Rutgers; M, change among viruses is intrinsic and the not only human immunodeficiency virus, Ricchetti, Pasteur Institute). This micro­ number of mutations simply related to mutate - but do not necessarily evolve heterogeneity leads to a population of the number of replication cycles (S. - at a high rate, and that recombination viral genomes known as quasispecies, Wain-Hobson, Pasteur Institute). result­ IS relatively common among RNA which are closely related but different ing in a genetically diverse population viruses. from one another. The proportions of capable of responding to very small Ever since von Magnus described these quasispecies change. depending on selective forces. changes in influenza virus populations both intrinsic error rates in polymerases Besides the heterogeneity resulting almost 40 years ago, investigators have and selective forces that may vary from single base mutations, a range of sought the cause of these changes. They according to the host environment. From strange and wonderful variations among have wondered whether such variations, the composition of different quasi­ viruses was presented. These included so easily detected in cell culture systems, species. viral replication rates, fitness satellite viruses of plant and animal *EMBO Workshop on Variation and Molecular Evolution of selection and mutation rates can all be viruses, where there is no commonality Viruses, Grignon, France. 7-11 July 1992. estimated In that ViruS population of sequence between the parasite and its Lifting the lid on enzymatic breakdown of lipids LIPASES are enzymes that hydrolyse triacylglycerol lipids into free fatty acids and glycerol - a crucial step in break­ ing down ingested fats in the gut. The pancreatic lipase enzyme's activity is greatly increased at the lipid-water in­ terface, when a short amphipathic helix, or lid (A), in the amino-terminal domain of the lipase (8), pops open and exposes the active site (C) of the enzyme to its lipid substrate (a phenomenon known as interfacial activation). The interaction of the lipase enzyme with the lipid inter­ face is very sensitive to the chemical nature of the lipid surface; in the pre­ sence of amphiphiles such as bile salts and phospholipids, the binding of the lipase to the lipid surface requires a small protein cofactor, colipase. The complex of these two molecules reveals that colipase binds to the carboxy­ terminal domain of the pancreatic lipase molecule (see the paper by H. van TiI­ beurgh et al. on page 159 of this issue). ® The co lipase's three hydrophobic fingers (F), here ball-and-stick groups, are sample hydrophobic presence of such inhibitors, then, the colipase cofactor may amino-acid side chains that point away from the lipase bring the larger lipase enzyme into close contact with the molecule but are on the same face of the complex as the lid Interface and allow opening of the lid to expose the active that covers the active site of the lipase molecule. The site, so facilitating the enzymatic breakdown of lipids. binding of lipase, but not colipase, to the lipid-water (Figure adapted from P. J. Kraulis J. appl. Ctystal/ogr. 24, interface is inhibited by amphiphiles (like bile salts). In the 946-950; 1991.) G. R, NATURE· VOL 359 . 10 SEPTEMBER 1992 107 © 1992 Nature Publishing Group NEWS AND VIEWS -DAEDALUS ~~~~~~~-, helper (G. Bruening, University of Cali­ One group is even attempting, so far fornia at Davis; W. Carman, Institute of without success, to approach this issue Know thyself! Virology, Glasgow); viroids, which are by analysis of monkey bones from Egyp­ THE victorian art of phrenology divided small RNA replicons, containing dupli­ tian tombs for simian immunodeficiency the brain into compartments. One part cated sequences (P. Keese, CSIRO, virus-like sequences (A. van der Kuyl, dealt with hope, another with Canberra); illegitimate recombinants University of Amsterdam). constructiveness, another with language among viruses containing either RNA or To population theorists, quasispecies, and so on. The strength of each faculty DNA genomes (H. Temin, University of recombinations and deletion mutants, could be judged by the enlargement of Wisconsin; M. Lai, University of South­ coupled with the relatively short genera­ the skull at that point. Feeling their eI11 California; G. Smith, University of tion times of viruses, offer interesting clients' skulls with sensitive fingers, Oxford); hypermutation of G to A in systems to test hypotheses vis a vis real popular phrenologists provided retrovirus genomes (J.-P. Vartanian, data. For instance, there is Muller's vocational guidance, character Pasteur Institute); nonreplicative mod­ ratchet, a hypothesis that states that assessment and psychiatric diagnosis. ification of nucleotides in RNA of para­ mutation will move a small population They even tried to detect an overactive myxoviruses (M. A. Billeter, University inexorably more distant from the most faculty from the warmth of the skull over of Zurich); and the insertion of host fit genotype; to ensure survival, such the relevant region. Nowadays, these sequences into the RNA of a flavivirus, driven populations gain stability through skills have practically died out. bovine viral diarrhoea virus. The inser­ increasing their population size or Daedalus plans to revive them. He tion introduces a change in a cleavage through recombination. Continuous pas­ points out that modern techniques such as computed X-ray tomography give us site, producing a new protein that saging of an RNA phage under nonselec­ direct access to the shape and size of changes the course of disease in persis­ tive conditions and measuring mutants the brain. Nuclear magnetic scanning, tently infected cows to death from and recombinants led to complete sup­ and especially positron-emission mucosal peeling within a few hours (N. port for this hypothesis (L. Chao, Uni­ imaging, can even map Its metabolic Tautz, Federal Research Centre for versity of Maryland). activity. So DREADCO technicians are Virus Disease of Animals, Tiibingen). Another successful use of mathematic­ now setting up a laboratory of Positron­ Results like these promise that differ­ al modelling was based on the predator­ Emission Phrenology to test the old ences in disease potential may indeed be prey relationship described for a defec­ ideas with modern rigour and explore due to heterogeneity in viral populations tive interfering particle and its helper new ones. in which chunks of genetic material are standard virus. Rather than regular cycl­ Volunteers for the new study will being inserted, deleted or otherwise ing between defective interfering parti­ simply lie In the PEP machine and altered. The challenge will be to dissect cles and standard virus, there was chao­ respond to requests to think about a out population changes in hosts during tic unpredictability even in a determinis­ particular topic or exercise some the evolving pathogenic events and to tic model (T. B. L. Kirkwood, National specific emotion. The site of sudden relate attenuation or virulence to each of Institute for Medical Research, Mill metabolic activity, or raised the particular variations found in these Hill). When mutations were added to concentration of the implicated viruses. the model, computer-simulated viral pas­ neurotransmitter, will then be displayed Hundreds of sequences from
Load more

Recommended publications
  • Rat CLPS / Colipase Protein (His Tag)
    Rat CLPS / Colipase Protein (His Tag) Catalog Number: 80729-R08H General Information SDS-PAGE: Gene Name Synonym: CLPS Protein Construction: A DNA sequence encoding the rat Clps (NP_037271.1) (Met1-Gln112) was expressed with a polyhistidine tag at the C-terminus. Source: Rat Expression Host: HEK293 Cells QC Testing Purity: > 95 % as determined by SDS-PAGE. Endotoxin: Protein Description < 1.0 EU per μg protein as determined by the LAL method. Colipase belongs to the colipase family. Structural studies of the complex Stability: and of colipase alone have revealed the functionality of its architecture. It is a small protein with five conserved disulphide bonds. Structural analogies Samples are stable for up to twelve months from date of receipt at -70 ℃ have been recognised between a developmental protein, the pancreatic lipase C-terminal domain, the N-terminal domains of lipoxygenases and the Predicted N terminal: Ala 18 C-terminal domain of alpha-toxin. Colipase can only be detected in Molecular Mass: pancreatic acinar cells, suggesting regulation of expression by tissue- specific elements. Colipase allows lipase to anchor noncovalently to the The recombinant rat Clps consists 106 amino acids and predicts a surface of lipid micelles, counteracting the destabilizing influence of molecular mass of 11.9 kDa. intestinal bile salts. Without colipase the enzyme is washed off by bile salts, which have an inhibitory effect on the lipase. Colipase is a cofactor needed Formulation: by pancreatic lipase for efficient dietary lipid hydrolysis. It binds to the C- terminal, non-catalytic domain of lipase, thereby stabilising as active Lyophilized from sterile PBS, pH 7.4.
    [Show full text]
  • Biochemical Properties of Pancreatic Colipase from the Common Stingray
    Ben Bacha et al. Lipids in Health and Disease 2011, 10:69 http://www.lipidworld.com/content/10/1/69 RESEARCH Open Access Biochemical properties of pancreatic colipase from the common stingray Dasyatis pastinaca Abir Ben Bacha†, Aida Karray†, Lobna Daoud, Emna Bouchaala, Madiha Bou Ali, Youssef Gargouri and Yassine Ben Ali* Background: Pancreatic colipase is a required co-factor for pancreatic lipase, being necessary for its activity during hydrolysis of dietary triglycerides in the presence of bile salts. In the intestine, colipase is cleaved from a precursor molecule, procolipase, through the action of trypsin. This cleavage yields a peptide called enterostatin knoswn, being produced in equimolar proportions to colipase. Results: In this study, colipase from the common stingray Dasyatis pastinaca (CoSPL) was purified to homogeneity. The purified colipase is not glycosylated and has an apparent molecular mass of around 10 kDa. The NH2-terminal sequencing of purified CoSPL exhibits more than 55% identity with those of mammalian, bird or marine colipases. CoSPL was found to be less effective activator of bird and mammal pancreatic lipases than for the lipase from the same specie. The apparent dissociation constant (Kd) of the colipase/lipase complex and the apparent Vmax of the colipase-activated lipase values were deduced from the linear curves of the Scatchard plots. We concluded that Stingray Pancreatic Lipase (SPL) has higher ability to interact with colipase from the same species than with the mammal or bird ones. Conclusion: The fact that colipase is a universal lipase cofactor might thus be explained by a conservation of the colipase-lipase interaction site.
    [Show full text]
  • Polymorphisms in PNLIP, Encoding Pancreatic Lipase, and Associations with Metabolic Traits
    J Hum Genet (2001) 46:320–324 © Jpn Soc Hum Genet and Springer-Verlag 2001 ORIGINAL ARTICLE Robert A. Hegele · D. Dan Ramdath · Matthew R. Ban Michael N. Carruthers · Christine V. Carrington Henian Cao Polymorphisms in PNLIP, encoding pancreatic lipase, and associations with metabolic traits Received: January 18, 2001 / Accepted: February 19, 2001 Abstract Pancreatic lipase (EC 3.1.1.3) is an exocrine se- Introduction cretion that hydrolyzes dietary triglycerides in the small intestine. We developed genomic amplification primers to sequence the 13 exons of PNLIP, which encodes pancreatic Pancreatic lipase (PL; EC 3.1.1.3), a 56-kD protein, is in- lipase, in order to screen for possible mutations in cell lines volved in the intestinal hydrolysis of dietary triglyceride to of four children with pancreatic lipase deficiency (OMIM fatty acids. PL deficiency (OMIM 246600) is associated with 246600). We found no missense or nonsense mutations in malabsorption of long-chain triglyceride fatty acids, failure these samples, but we found three silent single-nucleotide to thrive in infancy and childhood, and absence of PL secre- polymorphisms (SNPs), namely, 96A/C in exon 3, 486C/T in tion upon secretin stimulation (Sheldon 1964; Rey et al. exon 6, and 1359C/T in exon 13. In 50 normolipidemic 1966). PNLIP on chromosome 10q26.1 (Davis et al. 1991) is Caucasians, the PNLIP 96C and 486T alleles had frequen- a 13-exon gene that spans more than 20kb (Sims et al. 1993) cies of 0.083 and 0.150, respectively. The PNLIP 1359T and encodes the 465-amino acid PL mature protein (Lowe allele was absent from Caucasian, Chinese, South Asian, et al.
    [Show full text]
  • Human CLPS / Colipase Protein (His Tag)
    Human CLPS / Colipase Protein (His Tag) Catalog Number: 13631-H08B General Information SDS-PAGE: Gene Name Synonym: CLPS Protein Construction: A DNA sequence encoding the human CLPS (P04118) (Met 1-Gln 112) was fused with a polyhistidine tag at the C-terminus. Source: Human Expression Host: Baculovirus-Insect Cells QC Testing Purity: > 90 % as determined by SDS-PAGE Endotoxin: Protein Description < 1.0 EU per μg of the protein as determined by the LAL method Colipase belongs to the colipase family. Structural studies of the complex Stability: and of colipase alone have revealed the functionality of its architecture. It is a small protein with five conserved disulphide bonds. Structural analogies ℃ Samples are stable for up to twelve months from date of receipt at -70 have been recognised between a developmental protein, the pancreatic lipase C-terminal domain, the N-terminal domains of lipoxygenases and the Ala 18 Predicted N terminal: C-terminal domain of alpha-toxin. Colipase can only be detected in Molecular Mass: pancreatic acinar cells, suggesting regulation of expression by tissue- specific elements. Colipase allows lipase to anchor noncovalently to the The recombinant human CLPS consists of 105 amino acids and predicts a surface of lipid micelles, counteracting the destabilizing influence of molecular mass of 11.5 kDa. It migrates as an approximately 12 KDa band in intestinal bile salts. Without colipase the enzyme is washed off by bile salts, SDS-PAGE under reducing conditions. which have an inhibitory effect on the lipase. Colipase is a cofactor needed by pancreatic lipase for efficient dietary lipid hydrolysis. It binds to the C- Formulation: terminal, non-catalytic domain of lipase, thereby stabilising as active conformation and considerably increasing the overall hydrophobic binding Lyophilized from sterile PBS, 500mM NaCl, pH 7.0, 10% gly site.
    [Show full text]
  • Uniprot Acceprotiens 121 113 Ratio(113/12 114 Ratio
    Uniprot Acceprotiens 121 113 ratio(113/12 114 ratio(114/12 115 ratio(115/12 116 ratio(116/12 117 ratio(117/12 118 ratio(118/12 119 ratio(119/121) P02768 Serum albumin OS=Homo s666397.2 862466.6 1.29 593482.1 0.89 2220420.5 3.33 846469.3 1.27 634302.5 0.95 736961.1 1.11 842297.5 1.26 P02760 Protein AMBP OS=Homo s381627.7 294812.3 0.77 474165.8 1.24 203377.3 0.53 349197.6 0.92 346271.7 0.91 328356.1 0.86 411229.3 1.08 B4E1B2 cDNA FLJ53691, highly sim78511.8 107560.1 1.37 85218.8 1.09 199640.4 2.54 90022.3 1.15 73427.3 0.94 82722 1.05 102491.8 1.31 A0A0K0K1HEpididymis secretory sperm 3358.1 4584.8 1.37 4234.8 1.26 8496.1 2.53 4193.7 1.25 3507.1 1.04 3632.2 1.08 4873.3 1.45 D3DNU8 Kininogen 1, isoform CRA_302648.3 294936.6 0.97 257956.9 0.85 193831.3 0.64 290406.7 0.96 313453.3 1.04 279805.5 0.92 228883.9 0.76 B4E1C2 Kininogen 1, isoform CRA_167.9 229.7 1.37 263.2 1.57 278 1.66 326 1.94 265.5 1.58 290.3 1.73 341.5 2.03 O60494 Cubilin OS=Homo sapiens G40132.6 45037.5 1.12 38654.5 0.96 34055.8 0.85 39708.6 0.99 44702.9 1.11 45025.7 1.12 32701.3 0.81 P98164 Low-density lipoprotein rece40915.4 45344.8 1.11 35817.7 0.88 35721.8 0.87 42157.7 1.03 46693.4 1.14 48624 1.19 38847.7 0.95 A0A024RABHeparan sulfate proteoglyca46985.3 43536.1 0.93 49827.7 1.06 33964.3 0.72 44780.9 0.95 46858.6 1.00 47703.5 1.02 37785.7 0.80 P01133 Pro-epidermal growth factor 75270.8 73109.5 0.97 66336.1 0.88 56680.9 0.75 70877.8 0.94 76444.3 1.02 81110.3 1.08 65749.7 0.87 Q6N093 Putative uncharacterized pro47825.3 55632.5 1.16 48428.3 1.01 63601.5 1.33 65204.2 1.36 59384.5
    [Show full text]
  • Absorption and Metabolism of Lipid in Humans
    Lipids in Modern Nutrition, edited by M. Horisberger and U. Bracco. Nestle Nutrition, Vevey/Raven Press, New York © 1987. Absorption and Metabolism of Lipid in Humans Patrick Tso and Stuart W. Weidman Departments of Physiology and Medicine, The University of Tennessee Center for the Health Sciences, Memphis, Tennessee 38163 DIETARY LIPIDS Dietary lipids can provide as much as 40% of the daily caloric intake in the Western diet. The daily dietary intake of lipid by humans in the Western world ranges between 60 and 100 g (1,2). Triglyceride (TG) is the major dietary fat in humans. Long-chain fatty acids such as the oleate (18:1) and palmitate (16:0) are the major fatty acids (FA) present. In most infant diets, fat becomes a major en- ergy source. In human milk and in human formulas, 40% to 50% of the total calo- ries are present as fat (3). The human small intestine is presented daily with other lipids such as phospholipid (PL) and cholesterol and other sterols. Both PL and cholesterol are major constituents of bile. In humans, the biliary PL is a major contributor of the luminal PL. It has been calculated that 11 to 12 g of biliary PL enters the small intestinal lumen daily, whereas the dietary contribution is 1 to 2 g (4). The predominant sterol in the Western diet is cholesterol. However, plant sterols account for 20% to 25% of total dietary sterol (5-7). It is beyond the scope of this review to discuss the absorption of lipid soluble vitamins, and the interested readers should refer to the excellent review by Barrowman (8).
    [Show full text]
  • Quantitative Trait Loci Influencing Cholesterol and Phospholipid
    Quantitative trait loci influencing cholesterol and phospholipid phenotypes map to chromosomes that contain genes regulating blood pressure in the spontaneously hypertensive rat. A Bottger, … , T W Kurtz, M Pravenec J Clin Invest. 1996;98(3):856-862. https://doi.org/10.1172/JCI118858. Research Article The frequent coincidence of hypertension and dyslipidemia suggests that related genetic factors might underlie these common risk factors for cardiovascular disease. To investigate whether quantitative trait loci (QTLs) regulating lipid levels map to chromosomes known to contain genes regulating blood pressure, we used a genome scanning approach to map QTLs influencing cholesterol and phospholipid phenotypes in a large set of recombinant inbred strains and in congenic strains derived from the spontaneously hypertensive rat and normotensive Brown-Norway (BN.Lx) rat fed normal and high cholesterol diets. QTLs regulating lipid phenotypes were mapped by scanning the genome with 534 genetic markers. A significant relationship (P < 0.00006) was found between basal HDL2 cholesterol levels and the D19Mit2 marker on chromosome 19. Analysis of congenic strains of spontaneously hypertensive rat indicated that QTLs regulating postdietary lipid phenotypes exist also on chromosomes 8 and 20. Previous studies in the recombinant inbred and congenic strains have demonstrated the presence of blood pressure regulatory genes in corresponding segments of chromosomes 8, 19, and 20. These findings provide support for the hypothesis that blood pressure and certain lipid subfractions can be modulated by linked genes or perhaps even the same genes. Find the latest version: https://jci.me/118858/pdf Quantitative Trait Loci Influencing Cholesterol and Phospholipid Phenotypes Map to Chromosomes That Contain Genes Regulating Blood Pressure in the Spontaneously Hypertensive Rat Anita Bottger,* Hein A.
    [Show full text]
  • Bioinformatics and Evolution of Vertebrate Pancreatic Lipase And
    g in Geno nin m i ic M s ta & a P Holmes and Cox, J Data Mining in Genom Proteomics 2012, 3:1 D r f o Journal of o t e l o a DOI: 10.4172/2153-0602.1000112 m n r i c u s o J ISSN: 2153-0602 Data Mining in Genomics & Proteomics Research Article Open Access Bioinformatics and Evolution of Vertebrate Pancreatic Lipase and Related Proteins and Genes Roger S Holmes1,2,3* and Laura A Cox1,2 1Department of Genetics, Griffith University, Nathan, QLD, Australia 2Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA 3School of Biomolecular and Physical Sciences, Griffith University, Nathan, QLD, Australia Abstract Background: Pancreatic lipase (PTL) functions in the presence of colipase in the hydrolysis of emulsified fats in the small intestine following secretion from the pancreas. Pancreatic lipase related protein 1 (PLR1) is also found in pancreatic secretions and may perform a regulatory role in lipolysis; PLR2 catalyses pancreatic triglyceride and galactolipase reactions while PLR3 may serve a related but unknown lipase function. Comparative PTL, PLR1, PLR2 and PLR3 amino acid sequences and structures and gene locations and sequences were examined using data from several vertebrate genome projects. Methods: Sequence alignments and conserved predicted secondary and tertiary structures were studied and key amino acid residues and domains identified based on previous reports on human and pig PTL. Comparative analyses of vertebrate PTL-like genes were conducted using the UC Santa Cruz Genome Browser. Phylogeny studies investigated the evolution of these vertebrate PTL-like genes.
    [Show full text]
  • Physiological Parameters Governing the Action of Pancreatic Lipase
    Nutrition Research Reviews (2010), 23, 146–154 doi:10.1017/S0954422410000028 q The Authors 2010 Physiological parameters governing the action of pancreatic lipase Iain A. Brownlee1*, Deborah J. Forster1, Matthew D. Wilcox1, Peter W. Dettmar2, Chris J. Seal3 and Jeff P. Pearson1 1Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK 2Technostics Ltd, The Deep Business Centre, Hull HU1 4BG, UK 3Human Nutrition Research Centre, School of Agriculture, Food & Rural Development, Agriculture Building, Newcastle University, Newcastle upon Tyne NE1 7RU, UK The most widely used pharmacological therapies for obesity and weight management are based on inhibition of gastrointestinal lipases, resulting in a reduced energy yield of ingested foods by reducing dietary lipid absorption. Colipase-dependent pancreatic lipase is believed to be the major gastrointestinal enzyme involved in catalysis of lipid ester bonds. There is scant literature on the action of pancreatic lipase under the range of physiological conditions that occur within the human small intestine, and the literature that does exist is often contradictory. Due to the importance of pancreatic lipase activity to nutrition and weight management, the present review aims to assess the current body of knowledge with regards to the physiology behind the action of this unique gastrointestinal enzyme system. Existing data would suggest that pancreatic lipase activity is affected by intestinal pH, the presence of colipase and bile salts, but not by the physiological range of Ca ion concentration (as is commonly assumed). The control of secretion of pancreatic lipase and its associated factors appears to be driven by gastrointestinal luminal content, particularly the presence of acid or digested proteins and fats in the duodenal lumen.
    [Show full text]
  • Uniprot ID Title Mass 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
    Pancreatic duct fluidpy composite proteome p biomarkers Duct fluid numbers UniProt ID Title Mass 123456789101112131415161718192021222324252627 ALBU_HUMAN Serum albumin 71317 4.34 5.54 7.87 6.24 3.14 6.62 7.87 7.87 8.82 6.62 5.89 9.33 7.87 7.87 7.02 2.06 4.34 3.14 1.14 2.56 5.89 7.87 8.82 7.87 7.87 5.54 TRFE_HUMAN Serotransferrin 79280 0.44 2.44 3.95 3.52 0.15 1.86 3.12 5.51 6.82 2.44 0.81 3.52 3.95 3.52 5.82 1.08 0.73 1.08 0.26 0.98 1.38 5.82 3.12 5.22 3.95 1.99 APOA1_HUMAN Apolipoprotein A-I 30759 0.12 3.51 1 4.07 3.51 6.18 5.39 1.53 1 0.59 4.07 7.06 0.26 0.26 1 1 1.53 3.02 2.58 0.59 A1AT_HUMAN Alpha-1-antitrypsin 46878 0.26 1 1.93 1.16 0.17 1.33 1.93 2.69 5.82 1.71 2.69 2.42 2.69 3.3 1.51 2.16 1.71 0.47 0.17 0.59 1.71 0.36 2.16 1 1.71 1.16 1 TTHY_HUMAN Transthyretin 15991 0.24 0.24 1.39 0.24 0.24 APOA2_HUMAN Apolipoprotein A-II 11282 0.83 0.35 0.83 0.35 0.83 1.47 0.35 0.35 1.47 0.35 A1AG1_HUMAN Alpha-1-acid glycoprotein 1 23725 0.81 2.29 0.56 0.56 1.44 1.11 1.84 2.29 1.84 1.44 1.44 1.84 0.56 1.44 0.16 1.44 1.44 0.81 1.11 0.35 1.11 A1AG2_HUMAN Alpha-1-acid glycoprotein 2 23873 0.56 0.81 0.81 0.56 0.56 0.81 0.35 1.1 0.56 1.1 0.81 ZA2G_HUMAN Zinc-alpha-2-glycoprotein 34465 0.23 0.23 0.11 0.11 0.23 0.87 0.37 0.68 0.23 0.23 IC1_HUMAN Plasma protease C1 inhibitor 55347 0.58 0.58 0.58 0.8 0.48 0.92 0.48 0.58 0.48 0.48 0.92 0.8 0.48 0.58 0.07 0.68 0.38 0.07 A2MG_HUMAN Alpha-2-macroglobulin 164614 0.3 1.53 0.86 0.25 0.36 2.09 0.09 0.94 0.74 2.09 0.82 1.65 2.61 0.22 0.02 0.22 0.28 1.42 0.36 1.37 0.82 0.42 CERU_HUMAN Ceruloplasmin 122983 0.03 0.51
    [Show full text]
  • Structural Characterization of the Human Proteome
    Article Structural Characterization of the Human Proteome Arne Mu¨ller,1 Robert M. MacCallum,1,4 and Michael J.E. Sternberg1,2,3 1Biomolecular Modelling Laboratory, Cancer Research UK, London, United Kingdom; 2Department of Biological Sciences, Structural Bioinformatics Group, Imperial College of Science, Technology and Medicine, South Kensington, London, United Kingdom This paper reports an analysis of the encoded proteins (the proteome) of the genomes of human, fly, worm, yeast, and representatives of bacteria and archaea in terms of the three-dimensional structures of their globular domains together with a general sequence-based study. We show that 39% of the human proteome can be assigned to known structures. We estimate that for 77% of the proteome, there is some functional annotation, but only 26% of the proteome can be assigned to standard sequence motifs that characterize function. Of the human protein sequences, 13% are transmembrane proteins, but only 3% of the residues in the proteome form membrane-spanning regions. There are substantial differences in the composition of globular domains of transmembrane proteins between the proteomes we have analyzed. Commonly occurring structural superfamilies are identified within the proteome. The frequencies of these superfamilies enable us to estimate that 98% of the human proteome evolved by domain duplication, with four of the 10 most duplicated superfamilies specific for multicellular organisms. The zinc-finger superfamily is massively duplicated in human compared to fly and worm, and occurrence of domains in repeats is more common in metazoa than in single cellular organisms. Structural superfamilies over- and underrepresented in human disease genes have been identified.
    [Show full text]
  • Principles of Physiology of Lipid Digestion
    282 Principles of Physiology of Lipid Digestion E. Bauer*, S. Jakob1 and R. Mosenthin Institute of Animal Nutrition, University of Hohenheim, Emil-Wolff-Str. 10, 70599 Stuttgart, Germany ABSTRACT : The processing of dietary lipids can be distinguished in several sequential steps, including their emulsification, hydrolysis and micellization, before they are absorbed by the enterocytes. Emulsification of lipids starts in the stomach and is mediated by physical forces and favoured by the partial lipolysis of the dietary lipids due to the activity of gastric lipase. The process of lipid digestion continues in the duodenum where pancreatic triacylglycerol lipase (PTL) releases 50 to 70% of dietary fatty acids. Bile salts at low concentrations stimulate PTL activity, but higher concentrations inhibit PTL activity. Pancreatic triacylglycerol lipase activity is regulated by colipase, that interacts with bile salts and PTL and can release bile salt mediated PTL inhibition. Without colipase, PTL is unable to hydrolyse fatty acids from dietary triacylglycerols, resulting in fat malabsorption with severe consequences on bioavailability of dietary lipids and fat-soluble vitamins. Furthermore, carboxyl ester lipase, a pancreatic enzyme that is bile salt-stimulated and displays wide substrate reactivities, is involved in lipid digestion. The products of lipolysis are removed from the water-oil interface by incorporation into mixed micelles that are formed spontaneously by the interaction of bile salts. Monoacylglycerols and phospholipids enhance the ability of bile salts to form mixed micelles. Formation of mixed micelles is necessary to move the non-polar lipids across the unstirred water layer adjacent to the mucosal cells, thereby facilitating absorption. (Asian-Aust. J.
    [Show full text]