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991.
Eran Even-Tov Shira Omer Bendori Julie Valastyan Xiaobo Ke Shaul Pollak Tasneem Bareia Ishay Ben-Zion Bonnie L. Bassler Avigdor Eldar 《PLoS biology》2016,14(2)
Quorum sensing is a process of chemical communication that bacteria use to monitor cell density and coordinate cooperative behaviors. Quorum sensing relies on extracellular signal molecules and cognate receptor pairs. While a single quorum-sensing system is sufficient to probe cell density, bacteria frequently use multiple quorum-sensing systems to regulate the same cooperative behaviors. The potential benefits of these redundant network structures are not clear. Here, we combine modeling and experimental analyses of the Bacillus subtilis and Vibrio harveyi quorum-sensing networks to show that accumulation of multiple quorum-sensing systems may be driven by a facultative cheating mechanism. We demonstrate that a strain that has acquired an additional quorum-sensing system can exploit its ancestor that possesses one fewer system, but nonetheless, resume full cooperation with its kin when it is fixed in the population. We identify the molecular network design criteria required for this advantage. Our results suggest that increased complexity in bacterial social signaling circuits can evolve without providing an adaptive advantage in a clonal population. 相似文献
992.
George Tucker Po-Ru Loh Iona?M. MacLeod Ben?J. Hayes Michael?E. Goddard Bonnie Berger Alkes?L. Price 《American journal of human genetics》2015,97(5):677-690
Genetic prediction based on either identity by state (IBS) sharing or pedigree information has been investigated extensively with best linear unbiased prediction (BLUP) methods. Such methods were pioneered in plant and animal-breeding literature and have since been applied to predict human traits, with the aim of eventual clinical utility. However, methods to combine IBS sharing and pedigree information for genetic prediction in humans have not been explored. We introduce a two-variance-component model for genetic prediction: one component for IBS sharing and one for approximate pedigree structure, both estimated with genetic markers. In simulations using real genotypes from the Candidate-gene Association Resource (CARe) and Framingham Heart Study (FHS) family cohorts, we demonstrate that the two-variance-component model achieves gains in prediction r2 over standard BLUP at current sample sizes, and we project, based on simulations, that these gains will continue to hold at larger sample sizes. Accordingly, in analyses of four quantitative phenotypes from CARe and two quantitative phenotypes from FHS, the two-variance-component model significantly improves prediction r2 in each case, with up to a 20% relative improvement. We also find that standard mixed-model association tests can produce inflated test statistics in datasets with related individuals, whereas the two-variance-component model corrects for inflation. 相似文献
993.
994.
Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region 总被引:4,自引:0,他引:4
995.
Di Pasqua AJ Goodisman J Kerwood DJ Toms BB Dabrowiak JC 《Journal of inorganic biochemistry》2007,101(10):1438-1441
Using [(1)H,(15)N] heteronuclear single quantum coherance (HSQC) NMR and (15)N-labeled carboplatin, 1, we show that Jurkat cells affect the rate of disappearance of the HSQC NMR peak in culture medium for this Pt(2+) anticancer drug. The decay or disappearance rate constant for 1 in culture medium containing cells is k(1)=k(c)[CO(3)(2-)]+k(m)+k(u)N, where k(c) is the rate constant for reaction of 1 with carbonate in the medium, k(m) is the rate constant for reaction of 1 with all other components of the medium, and k(u) is the rate constant for reaction of 1 with cells having a number density N in the medium. Since Jurkat cells only take up a small amount of the platinum present in the medium (<1%), the observed disappearance of the HSQC NMR peak for 1 cannot be due to uptake of carboplatin by the cells. 相似文献
996.
Indole-3-butyric acid (IBA) is an endogenous auxin that acts in Arabidopsis primarily via its conversion to the principal auxin indole-3-acetic acid (IAA). Genetic and biochemical evidence indicates
that this conversion is similar to peroxisomal fatty acid β-oxidation, but the specific enzymes catalyzing IBA β-oxidation
have not been identified. We identified an IBA-response mutant (ibr3) with decreased responses to the inhibitory effects of IBA on root elongation or the stimulatory effects of IBA on lateral
root formation. However, ibr3 mutants respond normally to other forms of auxin, including IAA. The mutant seedlings germinate and develop normally, even
in the absence of sucrose, suggesting that fatty acid β-oxidation is unaffected. Additionally, double mutants between ibr3 and acx3, which is defective in an acyl-CoA oxidase acting in fatty acid β-oxidation, have enhanced IBA resistance, consistent with
a distinct role for IBR3. Positional cloning revealed that IBR3 encodes a putative acyl-CoA dehydrogenase with a consensus peroxisomal targeting signal. Based on the singular defect of this
mutant in responding to IBA, we propose that IBR3 may act directly in the oxidation of IBA to IAA.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users. 相似文献
997.
Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells 总被引:5,自引:0,他引:5
Maresz K Pryce G Ponomarev ED Marsicano G Croxford JL Shriver LP Ledent C Cheng X Carrier EJ Mann MK Giovannoni G Pertwee RG Yamamura T Buckley NE Hillard CJ Lutz B Baker D Dittel BN 《Nature medicine》2007,13(4):492-497
The cannabinoid system is immunomodulatory and has been targeted as a treatment for the central nervous system (CNS) autoimmune disease multiple sclerosis. Using an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we investigated the role of the CB(1) and CB(2) cannabinoid receptors in regulating CNS autoimmunity. We found that CB(1) receptor expression by neurons, but not T cells, was required for cannabinoid-mediated EAE suppression. In contrast, CB(2) receptor expression by encephalitogenic T cells was critical for controlling inflammation associated with EAE. CB(2)-deficient T cells in the CNS during EAE exhibited reduced levels of apoptosis, a higher rate of proliferation and increased production of inflammatory cytokines, resulting in severe clinical disease. Together, our results demonstrate that the cannabinoid system within the CNS plays a critical role in regulating autoimmune inflammation, with the CNS directly suppressing T-cell effector function via the CB(2) receptor. 相似文献
998.
999.
1000.
Darce JR Arendt BK Wu X Jelinek DF 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(11):7276-7286
BAFF plays a central role in B-lineage cell biology; however, the regulation of BAFF-binding receptor (BBR) expression during B cell activation and differentiation is not completely understood. In this study, we provide a comprehensive ex vivo analysis of BBRs in human B-lineage cells at various stages of maturation, as well as describe the events that drive and regulate receptor expression. Our data reveal that B-lineage cells ranging from naive to plasma cells (PCs), excluding bone marrow PCs, express BAFF-R uniformly. In contrast, only tonsillar memory B cells (MB) and PCs, from both tonsil and bone marrow tissues, express BCMA. Furthermore, we show that TACI is expressed by MB cells and PCs, as well as a subpopulation of activated CD27(neg) B cells. In this regard, we demonstrate that TACI is inducible early upon B cell activation and this is independent of B cell turnover. In addition, we found that TACI expression requires activation of the ERK1/2 pathway, since its expression was blocked by ERK1/2-specific inhibitors. Expression of BAFF-R and B cell maturation Ag (BCMA) is also highly regulated and we demonstrate that BCMA expression is only acquired in MB cells and in a manner accompanied by loss of BAFF-R expression. This inverse expression coincides with MB cell differentiation into Ig-secreting cells (ISC), since blocking differentiation inhibited both induction of BCMA expression and loss of BAFF-R. Collectively, our data suggest that the BBR profile may serve as a footprint of the activation history and stage of differentiation of normal human B cells. 相似文献