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21.
Ubiquitin specific protease 15 (USP15) functions in COP9 signalosome mediated regulation of protein degradation and cellular signaling through catalyzing the ubiquitin deconjugation reaction of a discrete number of substrates. It influences the stability of adenomatous polyposis coli, IκBα, caspase-3, and the human papillomavirus type 16 E6. USP15 forms a subfamily with USP4 and USP11 related through a shared presence of N-terminal "domain present in ubiquitin specific proteases" (DUSP) and "ubiquitin-like" (UBL) domains (DU subfamily). Here we report the 1.5 ? resolution crystal structure of the human USP15 N-terminal domains revealing a 80 ? elongated arrangement with the DU domains aligned in tandem. This architecture is generated through formation of a defined interface that is dominated by an intervening β-hairpin structure (DU finger) that engages in an intricate hydrogen-bonding network between the domains. The UBL domain is closely related to ubiquitin among β-grasp folds but is characterized by the presence of longer loop regions and different surface characteristics, indicating that this domain is unlikely to act as ubiquitin mimic. Comparison with the related murine USP4 DUSP-UBL crystal structure reveals that the main DU interdomain contacts are conserved. Analytical ultracentrifugation, small-angle X-ray scattering, and gel filtration experiments revealed that USP15 DU is monomeric in solution. Our data provide a framework to advance study of the structure and function of the DU subfamily. 相似文献
22.
Characterization of 3-chlorobenzoate degrading aerobic bacteria isolated under various environmental conditions 总被引:2,自引:0,他引:2
Krooneman J Sliekers AO Pedro Gomes TM Forney LJ Gottschal JC 《FEMS microbiology ecology》2000,32(1):53-59
The rates of bacterial growth in nature are often restricted by low concentrations of oxygen or carbon substrates. In the present study the metabolic properties of 24 isolates that had been isolated using various concentrations of 3-chlorobenzoate, benzoate and oxygen as well as using continuous culture at high and low growth rates were determined to investigate the effects of these parameters on the metabolism of monoaromatic compounds. Bacteria were enriched from different sampling sites and subsequently isolated. In batch culture this was done both under low oxygen (2% O(2)) and air-saturated concentrations. Chemostat enrichments were performed under either oxygen or 3-chlorobenzoate limiting conditions. Bacteria metabolizing aromatics with gentisate or protocatechuate as intermediates (gp bacteria) as well as bacteria metabolizing aromatic compounds via catechols (cat bacteria) were isolated from batch cultures when either benzoate or 3CBA were used as C sources, regardless of the enrichment conditions applied. In contrast, enrichments performed in chemostats at low dilution rates resulted in gp-type organisms only, whereas at high dilution rates cat-type organisms were enriched, irrespective of the oxygen and 3-chlorobenzoate concentration used during enrichment. It is noteworthy that the gp-type of bacteria possessed relatively low μ(max) values on 3CBA and benzoate along with relatively high substrate and oxygen affinities for these compounds. This is in contrast with cat-type of bacteria, which seemed to be characterized by high maximum specific growth rates on the aromatic substrates and relatively high apparent half saturation constants. In contrast, bacteria degrading chlorobenzoate via gentisate or protocatechuate may possibly be better adapted to conditions leading to growth at reduced rates such as low oxygen and low substrate concentrations. 相似文献
23.
RG Lockie AB Schultz SJ Callaghan CA Jordan TM Luczo MD Jeffriess 《Biology of sport / Institute of Sport》2015,32(1):41-51
There is little research investigating relationships between the Functional Movement Screen (FMS) and athletic performance in female athletes. This study analyzed the relationships between FMS (deep squat; hurdle step [HS]; in-line lunge [ILL]; shoulder mobility; active straight-leg raise [ASLR]; trunk stability push-up; rotary stability) scores, and performance tests (bilateral and unilateral sit-and-reach [flexibility]; 20-m sprint [linear speed]; 505 with turns from each leg; modified T-test with movement to left and right [change-of-direction speed]; bilateral and unilateral vertical and standing broad jumps; lateral jumps [leg power]). Nine healthy female recreational team sport athletes (age = 22.67 ± 5.12 years; height = 1.66 ± 0.05 m; body mass = 64.22 ± 4.44 kilograms) were screened in the FMS and completed the afore-mentioned tests. Percentage between-leg differences in unilateral sit-and-reach, 505 turns and the jumps, and difference between the T-test conditions, were also calculated. Spearman''s correlations (p ≤ 0.05) examined relationships between the FMS and performance tests. Stepwise multiple regressions (p ≤ 0.05) were conducted for the performance tests to determine FMS predictors. Unilateral sit-and-reach positive correlated with the left-leg ASLR (r = 0.704-0.725). However, higher-scoring HS, ILL, and ASLR related to poorer 505 and T-test performance (r = 0.722-0.829). A higher-scored left-leg ASLR related to a poorer unilateral vertical and standing broad jump, which were the only significant relationships for jump performance. Predictive data tended to confirm the correlations. The results suggest limitations in using the FMS to identify movement deficiencies that could negatively impact athletic performance in female team sport athletes. 相似文献
24.
BP ONeill TM Habermann TE Witzig M Rodriguez 《Cancer immunology, immunotherapy : CII》1999,16(3):211-215
Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone,
(HDMP) to prevent ‘trafficking’ of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of
its ability to stabilize the ‘blood brain barrier (BBB)’. Three men with newly diagnosed PCNSL, ages 62, 76 and 78 y, whose
survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy
alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did
die of systemic non-Hodgkin’s lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after
successful combined modality therapy and is alive 75+months after initial diagnosis without evidence of disease recurrence.
A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after
unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications.
The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase
2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70 y of age and older, a group of patients at high risk
for toxicity from intensive combined modality therapy. 相似文献
25.
Introduction
Management of osteoarthritis (OA) includes the use of non-pharmacological and pharmacological therapies. Although walking is commonly recommended for reducing pain and increasing physical function in people with OA, glucosamine sulphate has also been used to alleviate pain and slow the progression of OA. This study evaluated the effects of a progressive walking program and glucosamine sulphate intake on OA symptoms and physical activity participation in people with mild to moderate hip or knee OA. 相似文献26.
Amrita Pati Cecilia Vasquez-Robinet Lenwood S Heath Ruth Grene TM Murali 《BMC bioinformatics》2006,7(1):218-14
Background
Modeling of cis-elements or regulatory motifs in promoter (upstream) regions of genes is a challenging computational problem. In this work, set of regulatory motifs simultaneously present in the promoters of a set of genes is modeled as a biclique in a suitably defined bipartite graph. A biologically meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed by the combined analysis of genomic and gene expression data. Greater statistical significance is associated with a set of genes that shares a common set of regulatory motifs, while simultaneously exhibiting highly correlated gene expression under given experimental conditions. 相似文献27.
Miguel?Lacerda Penny?L?Moore Nobubelo?K?Ngandu Michael?Seaman Elin?S?Gray Ben?Murrell Mohan?Krishnamoorthy Molati?Nonyane Maphuti?Madiga Constantinos?Kurt?Wibmer Daniel?Sheward Robert?T?Bailer Hongmei?Gao Kelli?M?Greene Salim?S?Abdool?Karim John?R?Mascola Bette?TM?Korber David?C?Montefiori Lynn?Morris Carolyn?Williamson Cathal?SeoigheEmail author the CAVD-NSDP Consortium 《Virology journal》2013,10(1):347
Background
Identification of the epitopes targeted by antibodies that can neutralize diverse HIV-1 strains can provide important clues for the design of a preventative vaccine.Methods
We have developed a computational approach that can identify key amino acids within the HIV-1 envelope glycoprotein that influence sensitivity to broadly cross-neutralizing antibodies. Given a sequence alignment and neutralization titers for a panel of viruses, the method works by fitting a phylogenetic model that allows the amino acid frequencies at each site to depend on neutralization sensitivities. Sites at which viral evolution influences neutralization sensitivity were identified using Bayes factors (BFs) to compare the fit of this model to that of a null model in which sequences evolved independently of antibody sensitivity. Conformational epitopes were identified with a Metropolis algorithm that searched for a cluster of sites with large Bayes factors on the tertiary structure of the viral envelope.Results
We applied our method to ID50 neutralization data generated from seven HIV-1 subtype C serum samples with neutralization breadth that had been tested against a multi-clade panel of 225 pseudoviruses for which envelope sequences were also available. For each sample, between two and four sites were identified that were strongly associated with neutralization sensitivity (2ln(BF)?>?6), a subset of which were experimentally confirmed using site-directed mutagenesis.Conclusions
Our results provide strong support for the use of evolutionary models applied to cross-sectional viral neutralization data to identify the epitopes of serum antibodies that confer neutralization breadth.28.
Entomopathogenic nematodes (EPN) are efficient biological pest control agents. Population genetics studies on EPN are seldom
known. Therefore, it is of interest to evaluate the significance of molecular sampling method (MSM) for accuracy, time needed, and
cost effectiveness over traditional sampling method (TSM). The study was conducted at the Mohican Hills golf course at the state
of Ohio where the EPN H. bacteriophora has been monitored for 18 years. The nematode population occupies an area of
approximately 3700 m2 with density range from 0.25-2 per gram soil. Genetic diversity of EPN was studied by molecular sampling
method (MSM) and traditional sampling method (TSM) using the mitochondrial gene pcox1. The MSM picked 88% in compared to
TSM with only 30% of sequenced cox 1 gene. All studied genetic polymorphism measures (sequence and haplotype) showed high
levels of genetic diversity of MSM over TSM. MSM minimizes the chance of mitochondrial genes amplification from non target
organisms (insect or other contaminating microorganisms). Moreover, it allows the sampling of more individuals with a reliable
and credible representative sample size. Thus, we show that MSM supersedes TSM in labour intensity, time consumption and
requirement of no special experience and efficiency. 相似文献
29.
D. Besong Agbo H. Klafki G. Poschmann K. Seyfarth J. Genius C. Janßen K. Stühler W. Wurst H.E. Meyer M. Klingenspor J. Wiltfang 《Analytical biochemistry》2013
We report on the development of a novel assay protocol for the separation and detection of charge isoforms of DJ-1 in biological samples by automated capillary isoelectric focusing followed by immunological detection. DJ-1 (PARK7) is considered as a biomarker candidate for Parkinson’s disease and may potentially support the differentiation of clinical subtypes of the disease. The new method allows for separation and subsequent relative quantitative comparison of different isoforms of DJ-1 in biological samples. The assay was successfully applied to the analysis of DJ-1 isoform patterns in brains from mice subjected to normal or high-fat diet and revealed statistically significant group differences. Furthermore, in a pooled and concentrated sample of human cerebrospinal fluid that was depleted of albumin and immunoglobulin G, four different charge variants of DJ-1 could be detected. Taken together, the capillary isoelectric focusing immunoassay for DJ-1 represents a promising tool that may ultimately serve in clinical biomarker studies. 相似文献
30.
Monika Feigenbutz Rebecca Jones Tabot M. D. Besong Stephen E. Harding Phil Mitchell 《The Journal of biological chemistry》2013,288(22):15959-15970
Rrp6 is a key catalytic subunit of the nuclear RNA exosome that plays a pivotal role in the processing, degradation, and quality control of a wide range of cellular RNAs. Here we report our findings on the assembly of the complex involving Rrp6 and its associated protein Rrp47, which is required for many Rrp6-mediated RNA processes. Recombinant Rrp47 is expressed as a non-globular homodimer. Analysis of the purified recombinant Rrp6·Rrp47 complex revealed a heterodimer, suggesting that Rrp47 undergoes a structural reconfiguration upon interaction with Rrp6. Studies using GFP fusion proteins show that Rrp6 and Rrp47 are localized to the yeast cell nucleus independently of one another. Consistent with this data, Rrp6, but not Rrp47, is found associated with the nuclear import adaptor protein Srp1. We show that the interaction with Rrp6 is critical for Rrp47 stability in vivo; in the absence of Rrp6, newly synthesized Rrp47 is rapidly degraded in a proteasome-dependent manner. These data resolve independent nuclear import routes for Rrp6 and Rrp47, reveal a structural reorganization of Rrp47 upon its interaction with Rrp6, and demonstrate a proteasome-dependent mechanism that efficiently suppresses the expression of Rrp47 in the absence of Rrp6. 相似文献