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851.
Similarities and differences between amino acids define the rates at which they substitute for one another within protein sequences and the patterns by which these sequences form protein structures. However, there exist many ways to measure similarity, whether one considers the molecular attributes of individual amino acids, the roles that they play within proteins, or some nuanced contribution of each. One popular approach to representing these relationships is to divide the 20 amino acids of the standard genetic code into groups, thereby forming a simplified amino acid alphabet. Here, we develop a method to compare or combine different simplified alphabets, and apply it to 34 simplified alphabets from the scientific literature. We use this method to show that while different suggestions vary and agree in non-intuitive ways, they combine to reveal a consensus view of amino acid similarity that is clearly rooted in physico-chemistry. 相似文献
852.
Geun-Shik Lee Yuanzheng He Edward J. Dougherty Maria Jimenez-Movilla Matteo Avella Sean Grullon David S. Sharlin Chunhua Guo John A. Blackford Jr. Smita Awasthi Zhenhuan Zhang Stephen P. Armstrong Edra C. London Weiping Chen Jurrien Dean S. Stoney Simons Jr. 《The Journal of biological chemistry》2013,288(21):15167-15180
TTLL5/STAMP (tubulin tyrosine ligase-like family member 5) has multiple activities in cells. TTLL5 is one of 13 TTLLs, has polyglutamylation activity, augments the activity of p160 coactivators (SRC-1 and TIF2) in glucocorticoid receptor-regulated gene induction and repression, and displays steroid-independent growth activity with several cell types. To examine TTLL5/STAMP functions in whole animals, mice were prepared with an internal deletion that eliminated several activities of the Stamp gene. This mutation causes both reduced levels of STAMP mRNA and C-terminal truncation of STAMP protein. Homozygous targeted mutant (Stamptm/tm) mice appear normal except for marked decreases in male fertility associated with defects in progressive sperm motility. Abnormal axonemal structures with loss of tubulin doublets occur in most Stamptm/tm sperm tails in conjunction with substantial reduction in α-tubulin polyglutamylation, which closely correlates with the reduction in mutant STAMP mRNA. The axonemes in other structures appear unaffected. There is no obvious change in the organs for sperm development of WT versus Stamptm/tm males despite the levels of WT STAMP mRNA in testes being 20-fold higher than in any other organ examined. This defect in male fertility is unrelated to other Ttll genes or 24 genes previously identified as important for sperm function. Thus, STAMP appears to participate in a unique, tissue-selective TTLL-mediated pathway for α-tubulin polyglutamylation that is required for sperm maturation and motility and may be relevant for male fertility. 相似文献
853.
Ruodan Nan Stuart Tetchner Elizabeth Rodriguez Po-Jung Pao Jayesh Gor Imre Lengyel Stephen J. Perkins 《The Journal of biological chemistry》2013,288(26):19197-19210
The sub-retinal pigment epithelial deposits that are a hallmark of age-related macular
degeneration contain both C3b and millimolar levels of zinc. C3 is the central protein of
complement, whereas C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3.
During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor
H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical
ultracentrifugation and x-ray scattering. C3, C3u, and C3b associated strongly in >100
μm zinc, whereas C3c and C3d showed weak association. With zinc, C3 forms soluble
oligomers, whereas C3u and C3b precipitate. We conclude that the C3, C3u, and C3b association with
zinc depended on the relative positions of C3d and C3c in each protein. Computational predictions
showed that putative weak zinc binding sites with different capacities exist in all five proteins,
in agreement with experiments. Factor H forms large oligomers in >10 μm zinc. In
contrast to C3b or Factor H alone, the solubility of the central C3b-Factor H complex was much
reduced at 60 μm zinc and even more so at >100 μm zinc. The
removal of the C3b-Factor H complex by zinc explains the reduced C3u/C3b inactivation rates by zinc.
Zinc-induced precipitation may contribute to the initial development of sub-retinal pigment
epithelial deposits in the retina as well as reducing the progression to advanced age-related
macular degeneration in higher risk patients. 相似文献
854.
855.
856.
Ryan P. P. Shugg Ashley Thomson Natsuko Tanabe Adam Kashishian Bart H. Steiner Kamal D. Puri Alexey Pereverzev Brian J. Lannutti Frank R. Jirik S. Jeffrey Dixon Stephen M. Sims 《The Journal of biological chemistry》2013,288(49):35346-35357
Phosphatidylinositol 3-kinases (PI3K) participate in numerous signaling pathways, and control distinct biological functions. Studies using pan-PI3K inhibitors suggest roles for PI3K in osteoclasts, but little is known about specific PI3K isoforms in these cells. Our objective was to determine effects of isoform-selective PI3K inhibitors on osteoclasts. The following inhibitors were investigated (targets in parentheses): wortmannin and (pan-p110), PIK75 (α), GDC0941 (α, δ), TGX221 (β), AS252424 (γ), and IC87114 (δ). In addition, we characterized a new potent and selective PI3Kδ inhibitor, GS-9820, and explored roles of PI3K isoforms in regulating osteoclast function. Osteoclasts were isolated from long bones of neonatal rats and rabbits. Wortmannin, LY294002, GDC0941, IC87114, and GS-9820 induced a dramatic retraction of osteoclasts within 15–20 min to 65–75% of the initial area. In contrast, there was no significant retraction in response to vehicle, PIK75, TGX221, or AS252424. Moreover, wortmannin and GS-9820, but not PIK75 or TGX221, disrupted actin belts. We examined effects of PI3K inhibitors on osteoclast survival. Whereas PIK75, TGX221, and GS-9820 had no significant effect on basal survival, all blocked RANKL-stimulated survival. When studied on resorbable substrates, osteoclastic resorption was suppressed by wortmannin and inhibitors of PI3Kβ and PI3Kδ, but not other isoforms. These data are consistent with a critical role for PI3Kδ in regulating osteoclast cytoskeleton and resorptive activity. In contrast, multiple PI3K isoforms contribute to the control of osteoclast survival. Thus, the PI3Kδ isoform, which is predominantly expressed in cells of hematopoietic origin, is an attractive target for anti-resorptive therapeutics. LY294002相似文献
857.
Alberto J. León David Banner Luoling Xu Longsi Ran Zhiyu Peng Kang Yi Chao Chen Fengping Xu Jinrong Huang Zhen Zhao Zhen Lin Stephen H. S. Huang Yuan Fang Alyson A. Kelvin Ted M. Ross Amber Farooqui David J. Kelvin 《Journal of virology》2013,87(4):1957-1966
Ferrets have become an indispensable tool in the understanding of influenza virus virulence and pathogenesis. Furthermore, ferrets are the preferred preclinical model for influenza vaccine and therapeutic testing. Here we characterized the influenza infectome during the different stages of the infectious process in ferrets with and without prior specific immunity to influenza. RNA from lung tissue and lymph nodes from infected and naïve animals was subjected to next-generation sequencing, followed by de novo data assembly and annotation of the resulting sequences; this process generated a library comprising 13,202 ferret mRNAs. Gene expression profiles during pandemic H1N1 (pdmH1N1) influenza virus infection were analyzed by digital gene expression and solid support microarrays. As expected during primary infection, innate immune responses were triggered in the lung tissue; meanwhile, in the lymphoid tissue, genes encoding antigen presentation and maturation of effector cells of adaptive immunity increased dramatically. After 5 days postinfection, the innate immune gene expression was replaced by the adaptive immune response, which correlates with viral clearance. Reinfection with homologous pandemic influenza virus resulted in a diminished innate immune response, early adaptive immune gene regulation, and a reduction in clinical severity. The fully annotated ferret infectome will be a critical aid to the understanding of the molecular events that regulate disease severity and host-influenza virus interactions among seasonal, pandemic, and highly pathogenic avian influenzas. 相似文献
858.
James D. J. Gilbert Stephen J. Simpson 《Biological journal of the Linnean Society. Linnean Society of London》2013,109(4):802-816
Thrips of the genus Dunatothrips (Thysanoptera: Phlaeothripidae) construct domiciles by tying phyllodes of Australian Acacia trees together with silk‐like glue. Females often co‐found domiciles (pleometrosis), an apparently cooperative behaviour that potentially provides insights into social evolution. However, little is known about their basic natural history, limiting the scope for testable predictions. Here, we address this crucial prerequisite step by investigating some key outstanding questions in the most common species, D. aneurae, on its host, Acacia aneura. We detail distribution in space and time, mating, dispersal, domicile building and defence. Dunatothrips aneurae was distributed in loosely reproductively synchronized patches, and tended to prefer east‐facing, terminal phyllodes on thin‐phyllode A. aneura varieties. Mature domiciles contained middens, concentrated areas of waste, suggesting active maintenance of domiciles and the potential for the division of labour. We observed inbreeding and outbreeding. Dunatothrips aneurae males engaged in short, truncated matings with sisters before dispersing locally, mating with females in nearby immature domiciles; longer distance dispersal, although it must happen, is still undocumented. Males and females mated multiply. Lone females required male presence to initiate domiciles, constructed them without male help and lost wings on nesting by abscission. Silk production occurred well before egg laying. Aggression or defence appeared to be entirely absent. Taken together, these observations suggest that research into co‐founding behaviour should focus on: (1) local crowding; (2) lack of aggression; and (3) potential division of labour with respect to egg production, silk production and domicile maintenance. These results should provide a springboard for questions on the potential evolution of cooperation in this species. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109 , 802‐816. 相似文献
859.
Stephen J. Willson 《Bulletin of mathematical biology》2013,75(10):1840-1878
Trees are commonly utilized to describe the evolutionary history of a collection of biological species, in which case the trees are called phylogenetic trees. Often these are reconstructed from data by making use of distances between extant species corresponding to the leaves of the tree. Because of increased recognition of the possibility of hybridization events, more attention is being given to the use of phylogenetic networks that are not necessarily trees. This paper describes the reconstruction of certain such networks from the tree-average distances between the leaves. For a certain class of phylogenetic networks, a polynomial-time method is presented to reconstruct the network from the tree-average distances. The method is proved to work if there is a single reticulation cycle. 相似文献
860.
Athanasios Rizoulis David R. Elliott Stephen A. Rolfe Steven F. Thornton Steven A. Banwart Roger W. Pickup Julie D. Scholes 《Microbial ecology》2013,66(1):84-95
Polluted aquifers contain indigenous microbial communities with the potential for in situ bioremediation. However, the effect of hydrogeochemical gradients on in situ microbial communities (especially at the plume fringe, where natural attenuation is higher) is still not clear. In this study, we used culture-independent techniques to investigate the diversity of in situ planktonic and attached bacterial communities in a phenol-contaminated sandstone aquifer. Within the upper and lower plume fringes, denaturing gradient gel electrophoresis profiles indicated that planktonic community structure was influenced by the steep hydrogeochemical gradient of the plume rather than the spatial location in the aquifer. Under the same hydrogeochemical conditions (in the lower plume fringe, 30 m below ground level), 16S rRNA gene cloning and sequencing showed that planktonic and attached bacterial communities differed markedly and that the attached community was more diverse. The 16S rRNA gene phylogeny also suggested that a phylogenetically diverse bacterial community operated at this depth (30 mbgl), with biodegradation of phenolic compounds by nitrate-reducing Azoarcus and Acidovorax strains potentially being an important process. The presence of acetogenic and sulphate-reducing bacteria only in the planktonic clone library indicates that some natural attenuation processes may occur preferentially in one of the two growth phases (attached or planktonic). Therefore, this study has provided a better understanding of the microbial ecology of this phenol-contaminated aquifer, and it highlights the need for investigating both planktonic and attached microbial communities when assessing the potential for natural attenuation in contaminated aquifers. 相似文献