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61.
Shen H Ferguson SM Dephoure N Park R Yang Y Volpicelli-Daley L Gygi S Schlessinger J De Camilli P 《Molecular biology of the cell》2011,22(4):493-502
Clathrin-mediated endocytosis is a fundamental cellular process conserved from yeast to mammals and is an important endocytic route for the internalization of many specific cargos, including activated growth factor receptors. Here we examined changes in tyrosine phosphorylation, a representative output of growth factor receptor signaling, in cells in which endocytic clathrin-coated pits are frozen at a deeply invaginated state, that is, cells that lack dynamin (fibroblasts from dynamin 1, dynamin 2 double conditional knockout mice). The major change observed in these cells relative to wild-type cells was an increase in the phosphorylation state, and thus activation, of activated Cdc42-associated kinase (Ack), a nonreceptor tyrosine kinase. Ack is concentrated at clathrin-coated pits, and binds clathrin heavy chain via two clathrin boxes. RNA interference-based approaches and pharmacological manipulations further demonstrated that the phosphorylation of Ack requires both clathrin assembly into endocytic clathrin-coated pits and active Cdc42. These findings reveal a link between progression of clathrin-coated pits to endocytic vesicles and an activation-deactivation cycle of Ack. 相似文献
62.
Across bacterial phyla, distantly-related genomes with similar genomic GC content have similar patterns of amino acid usage 总被引:1,自引:0,他引:1
The GC content of bacterial genomes ranges from 16% to 75% and wide ranges of genomic GC content are observed within many bacterial phyla, including both gram negative and gram positive phyla. Thus, divergent genomic GC content has evolved repeatedly in widely separated bacterial taxa. Since genomic GC content influences codon usage, we examined codon usage patterns and predicted protein amino acid content as a function of genomic GC content within eight different phyla or classes of bacteria. We found that similar patterns of codon usage and protein amino acid content have evolved independently in all eight groups of bacteria. For example, in each group, use of amino acids encoded by GC-rich codons increased by approximately 1% for each 10% increase in genomic GC content, while the use of amino acids encoded by AT-rich codons decreased by a similar amount. This consistency within every phylum and class studied led us to conclude that GC content appears to be the primary determinant of the codon and amino acid usage patterns observed in bacterial genomes. These results also indicate that selection for translational efficiency of highly expressed genes is constrained by the genomic parameters associated with the GC content of the host genome. 相似文献
63.
Scott T Bates Donna Berg-Lyons J Gregory Caporaso William A Walters Rob Knight Noah Fierer 《The ISME journal》2011,5(5):908-917
Archaea, primarily Crenarchaeota, are common in soil; however, the structure of soil archaeal communities and the factors regulating their diversity and abundance remain poorly understood. Here, we used barcoded pyrosequencing to comprehensively survey archaeal and bacterial communities in 146 soils, representing a multitude of soil and ecosystem types from across the globe. Relative archaeal abundance, the percentage of all 16S rRNA gene sequences recovered that were archaeal, averaged 2% across all soils and ranged from 0% to >10% in individual soils. Soil C:N ratio was the only factor consistently correlated with archaeal relative abundances, being higher in soils with lower C:N ratios. Soil archaea communities were dominated by just two phylotypes from a constrained clade within the Crenarchaeota, which together accounted for >70% of all archaeal sequences obtained in the survey. As one of these phylotypes was closely related to a previously identified putative ammonia oxidizer, we sampled from two long-term nitrogen (N) addition experiments to determine if this taxon responds to experimental manipulations of N availability. Contrary to expectations, the abundance of this dominant taxon, as well as archaea overall, tended to decline with increasing N. This trend was coupled with a concurrent increase in known N-oxidizing bacteria, suggesting competitive interactions between these groups. 相似文献
64.
Cloern JE Knowles N Brown LR Cayan D Dettinger MD Morgan TL Schoellhamer DH Stacey MT van der Wegen M Wagner RW Jassby AD 《PloS one》2011,6(9):e24465
Background
Accumulating evidence shows that the planet is warming as a response to human emissions of greenhouse gases. Strategies of adaptation to climate change will require quantitative projections of how altered regional patterns of temperature, precipitation and sea level could cascade to provoke local impacts such as modified water supplies, increasing risks of coastal flooding, and growing challenges to sustainability of native species.Methodology/Principal Findings
We linked a series of models to investigate responses of California''s San Francisco Estuary-Watershed (SFEW) system to two contrasting scenarios of climate change. Model outputs for scenarios of fast and moderate warming are presented as 2010–2099 projections of nine indicators of changing climate, hydrology and habitat quality. Trends of these indicators measure rates of: increasing air and water temperatures, salinity and sea level; decreasing precipitation, runoff, snowmelt contribution to runoff, and suspended sediment concentrations; and increasing frequency of extreme environmental conditions such as water temperatures and sea level beyond the ranges of historical observations.Conclusions/Significance
Most of these environmental indicators change substantially over the 21st century, and many would present challenges to natural and managed systems. Adaptations to these changes will require flexible planning to cope with growing risks to humans and the challenges of meeting demands for fresh water and sustaining native biota. Programs of ecosystem rehabilitation and biodiversity conservation in coastal landscapes will be most likely to meet their objectives if they are designed from considerations that include: (1) an integrated perspective that river-estuary systems are influenced by effects of climate change operating on both watersheds and oceans; (2) varying sensitivity among environmental indicators to the uncertainty of future climates; (3) inevitability of biological community changes as responses to cumulative effects of climate change and other drivers of habitat transformations; and (4) anticipation and adaptation to the growing probability of ecosystem regime shifts. 相似文献65.
The white matter contains long-range connections between different brain regions and the organization of these connections holds important implications for brain function in health and disease. Tractometry uses diffusion-weighted magnetic resonance imaging (dMRI) to quantify tissue properties along the trajectories of these connections. Statistical inference from tractometry usually either averages these quantities along the length of each fiber bundle or computes regression models separately for each point along every one of the bundles. These approaches are limited in their sensitivity, in the former case, or in their statistical power, in the latter. We developed a method based on the sparse group lasso (SGL) that takes into account tissue properties along all of the bundles and selects informative features by enforcing both global and bundle-level sparsity. We demonstrate the performance of the method in two settings: i) in a classification setting, patients with amyotrophic lateral sclerosis (ALS) are accurately distinguished from matched controls. Furthermore, SGL identifies the corticospinal tract as important for this classification, correctly finding the parts of the white matter known to be affected by the disease. ii) In a regression setting, SGL accurately predicts “brain age.” In this case, the weights are distributed throughout the white matter indicating that many different regions of the white matter change over the lifespan. Thus, SGL leverages the multivariate relationships between diffusion properties in multiple bundles to make accurate phenotypic predictions while simultaneously discovering the most relevant features of the white matter. 相似文献
66.
67.
Gelkop S Gish GD Babichev Y Pawson T Isakov N 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(12):8123-8132
The Zap70 protein tyrosine kinase controls TCR-linked signal transduction pathways and is critical for T cell development and responsiveness. Following engagement of TCR, the Zap70 undergoes phosphorylation on multiple tyrosine residues that are implicated in the regulation of its catalytic activity and interaction with signaling effector molecules downstream of the TCR. We have shown previously that the CT10 regulator of kinase II (CrkII) adapter protein interacts with tyrosine-phosphorylated Zap70 in TCR-engaged T cells, and now extend these studies to show that Tyr315 in the Zap70 interdomain B region is the site of interaction with CrkII. A point mutation of Tyr315 (Y315F) eliminated the CrkII-Zap70 interaction capacity. Phosphorylation of Tyr315 and Zap70 association with CrkII were both dependent upon the Lck protein tyrosine kinase. Previous studies demonstrated the Tyr315 is the Vav-Src homology 2 (SH2) binding site, and that replacement of Tyr315 by Phe impaired the function of Zap70 in TCR signaling. However, fluorescence polarization-based binding studies revealed that the CrkII-SH2 and the Vav-SH2 bind a phosphorylated Tyr315-Zap70-derived peptide with affinities of a similar order of magnitude (Kd of 2.5 and 1.02 microM, respectively). The results suggest therefore that the biological functions attributed to the association of Zap70 with Vav following T cell activation may equally reflect the association of Zap70 with CrkII, and further support a regulatory role for CrkII in the TCR-linked signal transduction pathway. 相似文献
68.
Multiple V1/V2 env variants are frequently present during primary infection with human immunodeficiency virus type 1
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Ritola K Pilcher CD Fiscus SA Hoffman NG Nelson JA Kitrinos KM Hicks CB Eron JJ Swanstrom R 《Journal of virology》2004,78(20):11208-11218
Human immunodeficiency virus type 1 (HIV-1) exists as a complex population of multiple genotypic variants in persons with chronic infection. However, acute HIV-1 infection via sexual transmission is a low-probability event in which there is thought to be low genetic complexity in the initial inoculum. In order to assess the viral complexity present during primary HIV-1 infection, the V1/V2 and V3 variable regions of the env gene were examined by using a heteroduplex tracking assay (HTA) capable of resolving these genotypic variants. Blood plasma samples from 26 primary HIV-1-infected subjects were analyzed for their level of diversity. Half of the subjects had more than one V1/V2 viral variant during primary infection, indicating the frequent transmission of multiple variants. This observation is inconsistent with the idea of infrequent transmission based on a small transmitting inoculum of cell-free virus. In chronically infected subjects, the complexity of the viral populations was even greater in both the V1/V2 and the V3 regions than in acutely infected subjects, indicating that in spite of the presence of multiple variants in acute infection, the virus does pass through a genetic bottleneck during transmission. We also examined how well the infecting virus penetrated different anatomical compartments by using the HTA. Viral variants detected in blood plasma were compared to those detected in seminal plasma and/or cerebral spinal fluid of six individuals. The virus in each of these compartments was to a large extent identical to virus in blood plasma, a finding consistent with rapid penetration of the infecting variant(s). The low-probability transmission of multiple variants could be the result of transient periods of hyperinfectiousness or hypersusceptibility. Alternatively, the inefficient transfer of a multiply infected cell could account for both the low probability of transmission and the transfer of multiple variants. 相似文献
69.
Ariel Ohayon Yael Babichev Moran Galperin Amnon Altman Noah Isakov 《The journal of histochemistry and cytochemistry》2010,58(9):799-806
The protein kinase C-interacting cousin of thioredoxin (PICOT; also termed glutaredoxin 3) protein was discovered a decade ago as a protein kinase C θ (PKCθ)-binding protein in human T lymphocytes. PICOT possesses an amino-terminal monothiol thioredoxin-like domain and a carboxy-terminal tandem repeat of a monothiol glutaredoxin-like domain. Nevertheless, the enzymatic activities of PICOT and its potential substrates have not yet been characterized and its biological importance is unknown. Earlier studies reported the presence of PICOT in several different cell lines and tissues, but its expression pattern has not been thoroughly investigated. We performed Northern blot analysis of 19 different human organs and tissues and found the expression of PICOT mRNA in all organs and tissues tested. Western blot analysis confirmed the expression of PICOT at the protein level in all organs and tissues tested and showed, in addition, that PICOT and PKCθ expression in different tissues only partially overlap. These findings support the involvement of PICOT in biological functions that are independent of PKCθ. To analyze the in vivo expression pattern of PICOT within cells of different human organs, we performed immunohistochemical staining using PICOT-specific antibodies. Analysis of breast, pituitary, adrenal, pancreas, and kidney sections demonstrated a differential expression of PICOT in various cell types, with a predominant cytosolic staining of epithelial cells and low or undetectable levels of PICOT in the stroma. (J Histochem Cytochem 58:799–806, 2010) 相似文献
70.