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  • 1
    Publication Date: 2013-12-18
    Description: Arabinoxylan oligosaccharides (AXOS) are prebiotic carbohydrates with promising health-promoting properties that stimulate the activity of specific colon bacteria, in particular bifidobacteria. However, the mechanisms by which bifidobacterial strains break down these compounds in the colon is still unknown. This study investigates AXOS consumption of a large number of bifidobacterial strains (36), belonging to 11 different species, systematically. To determine their degradation mechanisms, all strains were grown on a mixture of arabinose and xylose, xylo-oligosaccharides, and complex AXOS molecules as the sole added energy sources. Based on principal component and cluster analyses of their different arabinose substituent and/or xylose backbone consumption patterns, five clusters that were species independent could be distinguished among the bifidobacterial strains tested. In parallel, the strains were screened for the presence of genes encoding several putative AXOS-degrading enzymes, but no clear-cut correlation could be made with the different degradation mechanisms. The intra- and interspecies differences in the consumption patterns of AXOS indicate that bifidobacterial strains could avoid competition among each other or even could cooperate jointly to degrade these complex prebiotics. The knowledge gained on the AXOS degradation mechanisms in bifidobacteria can be of importance in the rational design of prebiotics with tailor-made composition and thus increased specificity in the colon.
    Print ISSN: 0099-2240
    Electronic ISSN: 1098-5336
    Topics: Biology
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  • 2
    Publication Date: 2014-04-17
    Description: Environmental Science & Technology DOI: 10.1021/es4053279
    Print ISSN: 0013-936X
    Electronic ISSN: 1520-5851
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
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  • 3
    Publication Date: 2018-01-24
    Description: Journal of the American Chemical Society DOI: 10.1021/jacs.7b10524
    Print ISSN: 0002-7863
    Electronic ISSN: 1520-5126
    Topics: Chemistry and Pharmacology
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  • 4
    Publication Date: 2015-06-18
    Description: During development, cells interpret complex and often conflicting signals to make optimal decisions. Plant stomata, the cellular interface between a plant and the atmosphere, develop according to positional cues, which include a family of secreted peptides called epidermal patterning factors (EPFs). How these signalling peptides orchestrate pattern formation at a molecular level remains unclear. Here we report in Arabidopsis that Stomagen (also called EPF-LIKE9) peptide, which promotes stomatal development, requires ERECTA (ER)-family receptor kinases and interferes with the inhibition of stomatal development by the EPIDERMAL PATTERNING FACTOR 2 (EPF2)-ER module. Both EPF2 and Stomagen directly bind to ER and its co-receptor TOO MANY MOUTHS. Stomagen peptide competitively replaced EPF2 binding to ER. Furthermore, application of EPF2, but not Stomagen, elicited rapid phosphorylation of downstream signalling components in vivo. Our findings demonstrate how a plant receptor agonist and antagonist define inhibitory and inductive cues to fine-tune tissue patterning on the plant epidermis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532310/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532310/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jin Suk -- Hnilova, Marketa -- Maes, Michal -- Lin, Ya-Chen Lisa -- Putarjunan, Aarthi -- Han, Soon-Ki -- Avila, Julian -- Torii, Keiko U -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jun 25;522(7557):439-43. doi: 10.1038/nature14561. Epub 2015 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA [2] Department of Biology, University of Washington, Seattle, Washington 98195, USA. ; Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA. ; Department of Biology, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26083750" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; *Binding, Competitive ; DNA-Binding Proteins/*metabolism ; Enzyme Activation ; Hypocotyl/metabolism ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/metabolism ; Phosphorylation ; Plant Stomata/*growth & development/*metabolism ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; Receptors, Cell Surface/deficiency/genetics/*metabolism ; Seedlings/enzymology/metabolism ; Transcription Factors/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-07-09
    Description: Human cytomegalovirus is a widespread pathogen of major medical importance. It causes significant morbidity and mortality in immunocompromised individuals, and congenital infections can result in severe disabilities or stillbirth. Development of a vaccine is prioritized, but no candidate is close to release. Although correlations of viral genetic variability with pathogenicity are suspected, knowledge about the strain diversity of the 235-kb genome is still limited. In this study, 96 full-length human cytomegalovirus genomes from clinical isolates were characterized, quadrupling the amount of information available for full-genome analysis. These data provide the first high-resolution map of human cytomegalovirus interhost diversity and evolution. We show that cytomegalovirus is significantly more divergent than all other human herpesviruses and highlight hot spots of diversity in the genome. Importantly, 75% of strains are not genetically intact but contain disruptive mutations in a diverse set of 26 genes, including the immunomodulatory genes UL40 and UL111A. These mutants are independent of culture passage artifacts and circulate in natural populations. Pervasive recombination, which is linked to the widespread occurrence of multiple infections, was found throughout the genome. The recombination density was significantly higher than those of other human herpesviruses and correlated with strain diversity. While the overall effects of strong purifying selection on virus evolution are apparent, evidence of diversifying selection was found in several genes encoding proteins that interact with the host immune system, including UL18, UL40, UL142, and UL147. These residues may present phylogenetic signatures of past and ongoing virus-host interactions. IMPORTANCE Human cytomegalovirus has the largest genome of all viruses that infect humans. Currently, there is a great interest in establishing associations between genetic variants and strain pathogenicity of this herpesvirus. Since the number of publicly available full-genome sequences is limited, knowledge about strain diversity is highly fragmented and biased toward a small set of loci. Combined with our previous work, we have now contributed 101 complete genome sequences. We have used these data to conduct the first high-resolution analysis of interhost genome diversity, providing an unbiased and comprehensive overview of cytomegalovirus variability. These data are of major value to the development of novel antivirals and a vaccine and to identify potential targets for genotype-phenotype experiments. Furthermore, these data have enabled a thorough study of the evolutionary processes that have shaped cytomegalovirus diversity.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 6
    Publication Date: 2015-12-27
    Description: β-1,2-Linked mannosides are expressed on numerous cell-wall glycoconjugates of the opportunistic pathogen yeast Candida albicans . Several studies evidenced their implication in the host–pathogen interaction and virulence mechanisms. In the present study, we characterized the in vitro activity of CaBmt3, a β-1,2-mannosyltransferase involved in the elongation of β-1,2-oligomannosides oligomers onto the cell-wall polymannosylated N -glycans. A recombinant soluble enzyme Bmt3p was produced in Pichia pastoris and its enzyme activity was investigated using natural and synthetic oligomannosides as potential acceptor substrates. Bmt3p was shown to exhibit an exquisite enzymatic specificity by adding a single terminal β-mannosyl residue to α-1,2-linked oligomannosides capped by a Manβ1–2Man motif. Furthermore, we demonstrated that the previously identified CaBmt1 and CaBmt3 efficiently act together to generate Manβ1-2Manβ1–2[Manα1–2] n sequence from α-1,2-linked oligomannosides onto exogenous and endogenous substrates.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
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  • 7
    Publication Date: 2016-04-27
    Description: Background Blood outgrowth endothelial cells (BOECs) mediate therapeutic neovascularization in experimental models, but outgrowth characteristics and functionality of BOECs from patients with ischemic cardiomyopathy (ICMP) are unknown. We compared outgrowth efficiency and in vitro and in vivo functionality of BOECs derived from ICMP with BOECs from age-matched (ACON) and healthy young (CON) controls. Methods and Results We isolated 3.6±0.6 BOEC colonies/100 x 10 6 mononuclear cells (MNCs) from 60-mL blood samples of ICMP patients (n=45; age: 66±1 years; LVEF: 31±2%) versus 3.5±0.9 colonies/100 x 10 6 MNCs in ACON (n=32; age: 60±1 years) and 2.6±0.4 colonies/100 x 10 6 MNCs in CON (n=55; age: 34±1 years), P =0.29. Endothelial lineage (VEGFR2 + /CD31 + /CD146 + ) and progenitor (CD34 + /CD133 – ) marker expression was comparable in ICMP and CON. Growth kinetics were similar between groups ( P =0.38) and not affected by left ventricular systolic dysfunction, maladaptive remodeling, or presence of cardiovascular risk factors in ICMP patients. In vitro neovascularization potential, assessed by network remodeling on Matrigel and three-dimensional spheroid sprouting, did not differ in ICMP from (A)CON. Secretome analysis showed a marked proangiogenic profile, with highest release of angiopoietin-2 (1.4±0.3 x 10 5  pg/10 6 ICMP-BOECs) and placental growth factor (5.8±1.5 x 10 3  pg/10 6 ICMP BOECs), independent of age or ischemic disease. Senescence-associated β-galactosidase staining showed comparable senescence in BOECs from ICMP (5.8±2.1%; n=17), ACON (3.9±1.1%; n=7), and CON (9.0±2.8%; n=13), P =0.19. High-resolution microcomputed tomography analysis in the ischemic hindlimb of nude mice confirmed increased arteriogenesis in the thigh region after intramuscular injections of BOECs from ICMP ( P =0.025; n=8) and CON ( P =0.048; n=5) over vehicle control (n=8), both to a similar extent ( P= 0.831). Conclusions BOECs can be successfully culture-expanded from patients with ICMP. In contrast to impaired functionality of ICMP-derived bone marrow MNCs, BOECs retain a robust proangiogenic profile, both in vitro and in vivo, with therapeutic potential for targeting ischemic disease.
    Keywords: Cell Biology/Structural Biology, Cell Therapy, Vascular Biology, Chronic Ischemic Heart Disease, Heart Failure
    Electronic ISSN: 2047-9980
    Topics: Medicine
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  • 8
    Publication Date: 2013-10-19
    Description: Genetic mutations cause primary immunodeficiencies (PIDs) that predispose to infections. Here, we describe activated PI3K-delta syndrome (APDS), a PID associated with a dominant gain-of-function mutation in which lysine replaced glutamic acid at residue 1021 (E1021K) in the p110delta protein, the catalytic subunit of phosphoinositide 3-kinase delta (PI3Kdelta), encoded by the PIK3CD gene. We found E1021K in 17 patients from seven unrelated families, but not among 3346 healthy subjects. APDS was characterized by recurrent respiratory infections, progressive airway damage, lymphopenia, increased circulating transitional B cells, increased immunoglobulin M, and reduced immunoglobulin G2 levels in serum and impaired vaccine responses. The E1021K mutation enhanced membrane association and kinase activity of p110delta. Patient-derived lymphocytes had increased levels of phosphatidylinositol 3,4,5-trisphosphate and phosphorylated AKT protein and were prone to activation-induced cell death. Selective p110delta inhibitors IC87114 and GS-1101 reduced the activity of the mutant enzyme in vitro, which suggested a therapeutic approach for patients with APDS.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930011/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930011/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Angulo, Ivan -- Vadas, Oscar -- Garcon, Fabien -- Banham-Hall, Edward -- Plagnol, Vincent -- Leahy, Timothy R -- Baxendale, Helen -- Coulter, Tanya -- Curtis, James -- Wu, Changxin -- Blake-Palmer, Katherine -- Perisic, Olga -- Smyth, Deborah -- Maes, Mailis -- Fiddler, Christine -- Juss, Jatinder -- Cilliers, Deirdre -- Markelj, Gasper -- Chandra, Anita -- Farmer, George -- Kielkowska, Anna -- Clark, Jonathan -- Kracker, Sven -- Debre, Marianne -- Picard, Capucine -- Pellier, Isabelle -- Jabado, Nada -- Morris, James A -- Barcenas-Morales, Gabriela -- Fischer, Alain -- Stephens, Len -- Hawkins, Phillip -- Barrett, Jeffrey C -- Abinun, Mario -- Clatworthy, Menna -- Durandy, Anne -- Doffinger, Rainer -- Chilvers, Edwin R -- Cant, Andrew J -- Kumararatne, Dinakantha -- Okkenhaug, Klaus -- Williams, Roger L -- Condliffe, Alison -- Nejentsev, Sergey -- 095198/Wellcome Trust/United Kingdom -- 095198/Z/10/Z/Wellcome Trust/United Kingdom -- 095691/Wellcome Trust/United Kingdom -- BB/J004456/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_U105184308/Medical Research Council/United Kingdom -- U105184308/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 Nov 15;342(6160):866-71. doi: 10.1126/science.1243292. Epub 2013 Oct 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Cambridge, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24136356" target="_blank"〉PubMed〈/a〉
    Keywords: Class I Phosphatidylinositol 3-Kinases ; *Genetic Predisposition to Disease ; Humans ; Immunologic Deficiency Syndromes/*genetics/immunology/*pathology ; Lymphocytes/immunology ; Mutation ; Pedigree ; Phosphatidylinositol 3-Kinases/*genetics ; Phosphatidylinositol Phosphates/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Respiratory Tract Infections/*genetics/immunology/*pathology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 40 (1999), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Plant pathology 45 (1996), S. 0 
    ISSN: 1365-3059
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Two short sequences, situated in the bacterial 23S rDNA gene, were used as primers for the PCR detection of Erwinia amylovora bacteria. All 34 E. amylovora strains tested, coming from different geographical and host plant origins and of different virulence, produced a 565-bp PCR fragment. The E. amylovora bacteria could be discriminated from all other phytobacteria with which no PCR product was observed. Only Escherichia coli bacteria were cross-recognized by the production of a weaker PCR band of similar size to E. amylovora. In a fast PCR protocol, where two temperatures were cycled, E. amylovora in pure culture could be detected on gel at concentrations as low as 3 × 102 cfu mL–1. This corresponds to a detection limit of 1.5 bacteria per PCR. However, reliable PCR detection in woody host plant tissue was only obtained with PVP/PVPP-treated sample extracts. Using E. amylovora-spiked plant extracts and extracts of fruit tree shoots artificially infected with E. amylovora, the PCR detection sensitivity was determined to be 6.6 × 102 cfu mL–1 of extract. Starting from the plant samples, the PCR detection results were visualized on gels within 5 h.
    Type of Medium: Electronic Resource
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