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451.
De A Park JI Kawamura K Chen R Klein C Rauch R Mulders SM Sollewijn Gelpke MD Hsueh AJ 《Molecular endocrinology (Baltimore, Md.)》2006,20(10):2528-2538
452.
Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation 总被引:1,自引:0,他引:1 下载免费PDF全文
Mazroui R Sukarieh R Bordeleau ME Kaufman RJ Northcote P Tanaka J Gallouzi I Pelletier J 《Molecular biology of the cell》2006,17(10):4212-4219
Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2α phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2α phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2α to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2α phosphorylation-dependent and -independent pathways that target translation initiation. 相似文献
453.
Osmotic loading is known to modulate chondrocyte (cell) height, width and volume in articular cartilage. It is not known how cartilage architecture, especially the collagen fibril orientation, affects cell shape changes as a result of an osmotic challenge.Intact patellae of New Zealand white rabbits (n=6) were prepared for fluorescence imaging. Patellae were exposed to a hypotonic osmotic shock and cells were imaged before loading and 5–60 min after the osmotic challenge. Cell volumes and aspect ratios (height/width) were analyzed. A fibril-reinforced poroelastic swelling model with realistic primary collagen fibril orientations, i.e. horizontal, random and vertical orientation in the superficial, middle and deep zones, respectively and cells in different zones was used to estimate cell aspect ratios theoretically.As the medium osmolarity was reduced, cell aspect ratios decreased and volumes increased in the superficial zone of cartilage both experimentally (p<0.05) and theoretically. Theoretically determined aspect ratios of middle zone cells remained virtually constant, while they increased for deep zone cells as osmolarity was reduced.Findings of this study suggest that osmotic loading modulates chondrocyte shapes in accordance with the primary collagen fibril directions in articular cartilage. 相似文献
454.
We describe the case of a previously healthy young man who presented with headache, diplopia, nausea, vomiting, and bilateral papilledema. Magnetic resonance venography of the brain revealed thrombosis of the right transverse sinus. Blood tests showed elevated homocysteine levels, and coagulation studies revealed a homozygous C677T mutation and a heterozygous A1298C mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. The patient had no other etiology for venous thrombosis. We recommend screening patients who present with sinus thrombosis for MTHFR gene mutations. 相似文献
455.
Background: Consanguinity is a recognized common practice among marriages in the Middle East. Many studies have suggested a strong association between first cousin marriages and the incidence of autosomal recessive diseases and congenital anomalies. The objectives of this study were to study the prevalence of consanguinity among the marriages of Bekaa (a region in Lebanon) with its sociodemographic correlates, and to assess the prevalence of congenital anomalies associated with these marriages. Methods: This study was a cross-sectional study done in three of the major areas of the Bekaa region. The sample size consisted of 552 households chosen based on proportionate random sampling according to population size in each area. The survey was conducted based on face-to-face interview with a member of the couples of each household. Results: The overall prevalence of consanguineous marriages was reported to be 42% with first cousin marriage constituting around 31% of the total marriages. No association was found between different socioeconomic status (SES) correlates and first cousin marriages. Results showed a significant association between first cousin marriage and mental retardation, physical retardation, bilateral cleft lip +/- cleft palate, cystic fibrosis, and congenital blindness. Conclusion: In a population with a high degree of inbreeding, the formulation of a public health program with multiapproach strategy, including education about the anticipated genetic consequences, prenatal diagnosis, neonatal screening, and genetic counseling, is a necessity. 相似文献
456.
Sharon Guerstein Victoria Romeo-Aznar Maayan Dekel Oren Miron Nadav Davidovitch Rami Puzis Shai Pilosof 《PLoS computational biology》2021,17(8)
Social distancing is an effective population-level mitigation strategy to prevent COVID19 propagation but it does not reduce the number of susceptible individuals and bears severe social consequences—a dire situation that can be overcome with the recently developed vaccines. Although a combination of these interventions should provide greater benefits than their isolated deployment, a mechanistic understanding of the interplay between them is missing. To tackle this challenge we developed an age-structured deterministic model in which vaccines are deployed during the pandemic to individuals who do not show symptoms. The model allows for flexible and dynamic prioritization strategies with shifts between target groups. We find a strong interaction between social distancing and vaccination in their effect on the proportion of hospitalizations. In particular, prioritizing vaccines to elderly (60+) before adults (20-59) is more effective when social distancing is applied to adults or uniformly. In addition, the temporal reproductive number Rt is only affected by vaccines when deployed at sufficiently high rates and in tandem with social distancing. Finally, the same reduction in hospitalization can be achieved via different combination of strategies, giving decision makers flexibility in choosing public health policies. Our study provides insights into the factors that affect vaccination success and provides methodology to test different intervention strategies in a way that will align with ethical guidelines. 相似文献
457.
Hannoush RN 《PloS one》2008,3(10):e3498
The Wnt/beta-catenin signal transduction pathway regulates a broad range of developmental processes. Aberrant activation of the Wnt pathway leads to cancer and degenerative diseases. beta-catenin is a key signaling molecule that is frequently used as a direct monitor of Wnt pathway activation. This paper describes a multi-parametric method for quantitative analysis of cellular beta-catenin protein levels in a rapid and high-throughput manner. The assay offers temporally resolved detection of Wnt-stimulated accumulation of beta-catenin, simultaneously detecting cell number, and it sheds light onto the kinetics of posttranslational stabilization of beta-catenin. 相似文献
458.
Doherty EM Retz D Gavva NR Tamir R Treanor JJ Norman MH 《Bioorganic & medicinal chemistry letters》2008,18(6):1830-1834
8-(6-(4-(Trifluoromethyl)phenyl)pyrimidin-4-ylamino)-1,2,3,4-tetrahydronaphthalen-2-ol (4) and analogs (5-10) were shown to be potent inhibitors of human and rat TRPV1 in vitro with increased solubility over our previous series. Synthesis, SAR, and improvements in metabolic stability and absorption of these compounds are described herein. 相似文献
459.
Westaway SM Thompson M Rami HK Stemp G Trouw LS Mitchell DJ Seal JT Medhurst SJ Lappin SC Biggs J Wright J Arpino S Jerman JC Cryan JE Holland V Winborn KY Coleman T Stevens AJ Davis JB Gunthorpe MJ 《Bioorganic & medicinal chemistry letters》2008,18(20):5609-5613
6-Phenylnicotinamide (2) was previously identified as a potent TRPV1 antagonist with activity in an in vivo model of inflammatory pain. Optimization of this lead through modification of both the biaryl and heteroaryl components has resulted in the discovery of 6-(4-fluorophenyl)-2-methyl-N-(2-methylbenzothiazol-5-yl)nicotinamide (32; SB-782443) which possesses an excellent overall profile and has been progressed into pre-clinical development. 相似文献
460.
Korhonen RK Koistinen A Konttinen YT Santavirta SS Lappalainen R 《Biomedical engineering online》2005,4(1):32