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151.
It has been suggested that bacterial cells communicate by releasing and sensing small diffusible signal molecules in a process commonly known as quorum sensing (QS). It is generally assumed that QS is used to coordinate cooperative behaviours at the population level. However, evolutionary theory predicts that individuals who communicate and cooperate can be exploited. Here we examine the social evolution of QS experimentally in the opportunistic pathogen Pseudomonas aeruginosa, and show that although QS can provide a benefit at the group level, exploitative individuals can avoid the cost of producing the QS signal or of performing the cooperative behaviour that is coordinated by QS, and can therefore spread. We also show that a solution to the problem of exploitation is kin selection, if interacting bacterial cells tend to be close relatives. These results show that the problem of exploitation, which has been the focus of considerable attention in animal communication, also arises in bacteria. 相似文献
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154.
Kooner JS Saleheen D Sim X Sehmi J Zhang W Frossard P Been LF Chia KS Dimas AS Hassanali N Jafar T Jowett JB Li X Radha V Rees SD Takeuchi F Young R Aung T Basit A Chidambaram M Das D Grundberg E Hedman AK Hydrie ZI Islam M Khor CC Kowlessur S Kristensen MM Liju S Lim WY Matthews DR Liu J Morris AP Nica AC Pinidiyapathirage JM Prokopenko I Rasheed A Samuel M Shah N Shera AS Small KS Suo C Wickremasinghe AR Wong TY Yang M Zhang F;DIAGRAM;MuTHER Abecasis GR Barnett AH Caulfield M Deloukas P 《Nature genetics》2011,43(10):984-989
We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D. 相似文献
155.
Renna MD Oyadeyi AS Bossi E Kottra G Peres A 《Cellular and molecular life sciences : CMLS》2011,68(17):2961-2975
The functional and structural basis of reverse operation of PepT1 has been studied in Xenopus oocytes expressing the wild-type
and mutated forms of this protein. Using brief pulses from a negative holding potential, wild-type and Arg282 mutants exhibit
outward currents in the presence of Gly-Gln. The reversal potential of these currents is affected by both pH and substrate
concentration, confirming coupled transport in the wild type and in the mutants as well. Long-lasting voltage and current-clamp
experiments show that the outward currents are only temporary, and reflect accumulation and/or depletion effects near the
membrane. The ability to operate in reverse mode was confirmed in all isoforms by intracellular injection of substrate. The
role of Arg282 and Asp341 in the reverse transport was also investigated using charged substrates. Positive Lys-Gly (but not
Gly-Lys) showed enhanced transport currents in the Arg282 mutants. In contrast, negative Gly-Asp and Asp-Gly elicited modest
currents in all isoforms. 相似文献
156.
The intersection between art, poetry, philosophy and science was the leitmotif which guided the lives and careers of romantic natural philosophers including that of the Danish natural philosopher, H. C. Ørsted. A simple model of Ørsted’s career would be one in which it was framed by two periods of philosophical speculation: the youth’s curious and idealistic interest in new attractive thoughts and the experienced man’s mature reflections at the end of his life. We suggest that a closer look at the epistemological aspects of his works on the theory of beauty reveals a connection between this late work and his early philosophical work including experimental philosophy, but also with the work in teaching and textbook writing, that lies in between. The latter includes Ørsted’s view on the application of mathematics in natural philosophy as well as his failed attempt at a genetic presentation of elementary geometry. 相似文献
157.
Willer T Lee H Lommel M Yoshida-Moriguchi T de Bernabe DB Venzke D Cirak S Schachter H Vajsar J Voit T Muntoni F Loder AS Dobyns WB Winder TL Strahl S Mathews KD Nelson SF Moore SA Campbell KP 《Nature genetics》2012,44(5):575-580
Walker-Warburg syndrome (WWS) is clinically defined as congenital muscular dystrophy that is accompanied by a variety of brain and eye malformations. It represents the most severe clinical phenotype in a spectrum of diseases associated with abnormal post-translational processing of a-dystroglycan that share a defect in laminin-binding glycan synthesis1. Although mutations in six genes have been identified as causes of WWS, only half of all individuals with the disease can currently be diagnosed on this basis2. A cell fusion complementation assay in fibroblasts from undiagnosed individuals with WWS was used to identify five new complementation groups. Further evaluation of one group by linkage analysis and targeted sequencing identified recessive mutations in the ISPD gene (encoding isoprenoid synthase domain containing). The pathogenicity of the identified ISPD mutations was shown by complementation of fibroblasts with wild-type ISPD. Finally, we show that recessive mutations in ISPD abolish the initial step in laminin-binding glycan synthesis by disrupting dystroglycan O-mannosylation. This establishes a new mechanism for WWS pathophysiology. 相似文献
158.
Kostyukova AS 《Cellular and molecular life sciences : CMLS》2008,65(4):563-569
The tropomodulins are a family of proteins that cap the slow-growing (pointed) end of actin filaments and require tropomyosin
for optimal function. Tropomodulin is an elongated molecule with a molecular mass of about 40 kDa. The C-terminal half of
tropomodulin contains one compact cooperatively melting domain, whereas the N-terminal half has no cooperatively melting structure.
The N-terminal half of tropomodulin contains two tropomysin-binding sites and a tropomyosin-dependent actin-binding site,
the tropomyosin-independent actin-binding site being located at the C terminus. One tropomodulin molecule binds two tropomyosin
molecules, and thus one molecule of tropomodulin is necessary and sufficient for capping at the pointed end. Tropomyosin/tropomodulin
interactions are isoform specific. Differences in tropomyosin affinity for the two binding sites in tropomodulin may regulate
its correct positioning at the pointed end as well as effectiveness of capping the actin filament.
Received 30 July 2007; received after revision 2 October 2007; accepted 10 October 2007 相似文献
159.
Weedon MN Lango H Lindgren CM Wallace C Evans DM Mangino M Freathy RM Perry JR Stevens S Hall AS Samani NJ Shields B Prokopenko I Farrall M Dominiczak A;Diabetes Genetics Initiative;Wellcome Trust Case Control Consortium Johnson T Bergmann S Beckmann JS Vollenweider P Waterworth DM Mooser V Palmer CN Morris AD Ouwehand WH;Cambridge GEM Consortium Zhao JH Li S Loos RJ Barroso I Deloukas P Sandhu MS Wheeler E Soranzo N Inouye M Wareham NJ Caulfield M Munroe PB Hattersley AT McCarthy MI Frayling TM 《Nature genetics》2008,40(5):575-583
Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait. 相似文献
160.