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171.
Caburet S Zavadakova P Ben-Neriah Z Bouhali K Dipietromaria A Charon C Besse C Laissue P Chalifa-Caspi V Christin-Maitre S Vaiman D Levi G Veitia RA Fellous M 《PloS one》2012,7(3):e33412
Background
The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10–15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients.Methodology/Principal Findings
We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LODmax of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations.Conclusions/Significance
We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function. 相似文献172.
Shaffer VA Boerma M Buonanno M Costes S Criswell T Gonon G Pandey BN Pinto M Rockwell S 《Radiation research》2012,178(1):99-100
The Radiation Research Podcast was funded just over five years ago by a few Radiation Research Society members. To date, the volunteers running the podcast have produced and published online, open access, over 70 audio interviews. The program includes monthly interviews with authors of articles, award winners, and other recordings at conferences, such as round table discussions. We here present an overview of the podcast, from its creation to its fifth birthday, to explain how it is working, how the featured interviews are scheduled, and what future directions are taken. So, stay tuned! 相似文献
173.
Avihai Yacovan Rachel Ozeri Tzofit Kehat Sima Mirilashvili Daniel Sherman Alex Aizikovich Alina Shitrit Efrat Ben-Zeev Nili Schutz Osnat Bohana-Kashtan Alexander Konson Vered Behar Oren M. Becker 《Bioorganic & medicinal chemistry letters》2012,22(20):6460-6468
Cancer cells preferentially use glycolysis rather than oxidative phosphorylation for their rapid growth. They consume large amount of glucose to produce lactate even when oxygen is abundant, a phenomenon known as the Warburg effect. This metabolic change originates from a shift in the expression of alternative spliced isoforms of the glycolytic enzyme pyruvate kinase (PK), from PKM1 to PKM2. While PKM1 is constitutively active, PKM2 is switched from an inactive dimer form to an active tetramer form by small molecule activators. The prevalence of PKM2 in cancer cells relative to the prevalence of PKM1 in many normal cells, suggests a therapeutic strategy whereby activation of PKM2 may counter the abnormal cellular metabolism in cancer cells, and consequently decreased cellular proliferation. Herein we describe the discovery and optimization of a series of PKM2 activators derived from the 2-((2,3-dihydrobenzo[b][1,4] dioxin-6-yl)thio)-1-(2-methyl-1-(methylsulfonyl)indolin-5-yl) ethanone scaffold. The synthesis, SAR analysis, enzyme active site docking, enzymatic reaction kinetics, selectivity and pharmaceutical properties are discussed. 相似文献
174.
175.
N Bachner-Hinenzon O Ertracht A Malka M Leitman Z Vered O Binah D Adam 《American journal of physiology. Heart and circulatory physiology》2012,303(5):H549-H558
Myocardial infarction (MI) injury extends from the endocardium toward the epicardium. This phenomenon should be taken into consideration in the detection of MI. To study the extent of damage at different stages of MI, we hypothesized that measurement of layer-specific strain will allow better delineation of the MI extent than total wall thickness strain at acute stages but not at chronic stages, when fibrosis and remodeling have already occurred. After baseline echocardiography scans had been obtained, 24 rats underwent occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion. Thirteen rats were rescanned at 24 h post-MI and eleven rats at 2 wk post-MI. Next, rats were euthanized, and histological analysis for MI size was performed. Echocardiographic scans were postprocessed by a layer-specific speckle tracking program to measure the peak circumferential strain (S(C)(peak)) at the endocardium, midlayer, and epicardium as well as total wall thickness S(C)(peak). Linear regression for MI size versus S(C)(peak) showed that the slope was steeper for the endocardium compared with the other layers (P < 0.001), meaning that the endocardium was more sensitive to MI size than the other layers. Moreover, receiver operating characteristics analysis yielded better sensitivity and specificity in the detection of MI using endocardial S(C)(peak) instead of total wall thickness S(C)(peak) at 24 h post-MI (P < 0.05) but not 2 wk later. In conclusion, at acute stages of MI, before collagen deposition, scar tissue formation, and remodeling have occurred, damage may be nontransmural, and thus the use of endocardial S(C)(peak) is advantageous over total wall thickness S(C)(peak). 相似文献
176.
Maytal-Kivity V Pick E Piran R Hofmann K Glickman MH 《The international journal of biochemistry & cell biology》2003,35(5):706-715
The COP9 signalosome (CSN), the lid subcomplex of the proteasome and translational initiation factor 3 (eIF3) share structural similarities and are often referred to as the PCI family of complexes. In multicellular eukaryotes, the CSN is highly conserved as an 8-subunit complex but in Saccharomyces cerevisiae the complex is rather divergent. We further characterize the composition and properties of the CSN in budding yeast and its interactions with these related complexes. Using the generalized profile method we identified CSN candidates, four with PCI domains: Csn9, Csn10, Pci8/Csn11, and Csn12, and one with an MPN domain, Csn5/Rri1. These proteins and an additional interactor, Csi1, were tested for pairwise interactions by yeast two-hybrid and were found to form a cluster surrounding Csn12. Csn5 and Csn12 cofractionate in a complexed form with an apparent molecular weight of roughly 250kDa. However, Csn5 migrates as a monomer in Deltacsn12 supporting the pivotal role of Csn12 in stabilizing the complex. Confocal fluorescence microscopy detects GFP-tagged Csn5 preferentially in the nucleus, whereas in absence of Csn12, Csn10, Pci8/Csn11, or Csi1, Csn5 is delocalized throughout the cell, indicating that multiple subunits are required for nuclear localization of Csn5. Two CSN subunits, Csn9 and Csi1, interact with the proteasome lid subunit Rpn5. Pci8/Csn11 has previously been shown to interact with eIF3. Together, these results point to a network of interactions between these three structurally similar, yet functionally diverse, complexes. 相似文献
177.
Padler-Karavani V Song X Yu H Hurtado-Ziola N Huang S Muthana S Chokhawala HA Cheng J Verhagen A Langereis MA Kleene R Schachner M de Groot RJ Lasanajak Y Matsuda H Schwab R Chen X Smith DF Cummings RD Varki A 《The Journal of biological chemistry》2012,287(27):22593-22608
DNA and protein arrays are commonly accepted as powerful exploratory tools in research. This has mainly been achieved by the establishment of proper guidelines for quality control, allowing cross-comparison between different array platforms. As a natural extension, glycan microarrays were subsequently developed, and recent advances using such arrays have greatly enhanced our understanding of protein-glycan recognition in nature. However, although it is assumed that biologically significant protein-glycan binding is robustly detected by glycan microarrays, there are wide variations in the methods used to produce, present, couple, and detect glycans, and systematic cross-comparisons are lacking. We address these issues by comparing two arrays that together represent the marked diversity of sialic acid modifications, linkages, and underlying glycans in nature, including some identical motifs. We compare and contrast binding interactions with various known and novel plant, vertebrate, and viral sialic acid-recognizing proteins and present a technical advance for assessing specificity using mild periodate oxidation of the sialic acid chain. These data demonstrate both the diversity of sialic acids and the analytical power of glycan arrays, showing that different presentations in different formats provide useful and complementary interpretations of glycan-binding protein specificity. They also highlight important challenges and questions for the future of glycan array technology and suggest that glycan arrays with similar glycan structures cannot be simply assumed to give similar results. 相似文献
178.
Eichler J Irihimovitch V 《BioEssays : news and reviews in molecular, cellular and developmental biology》2003,25(12):1154-1157
The translocation of proteins across membranes is a central problem in biology. Regardless of the system in question, delivering proteins across a given membrane relies on many of the same basic themes. At the same time, however, each membrane translocation system, be it signal-gated or signal-assembled, makes use of components unique to that system. The latest findings on protein translocation across a variety of biological membranes have been presented in a recent review article. 相似文献
179.
Rosen N Chalifa-Caspi V Shmueli O Adato A Lapidot M Stampnitzky J Safran M Lancet D 《Bioinformatics (Oxford, England)》2003,19(Z1):i222-i224
MOTIVATION:Despite the numerous available whole-genome mapping resources, no comprehensive, integrated map of the human genome yet exists. RESULTS: GeneLoc, software adjunct to GeneCards and UDB, integrates gene lists by comparing genomic coordinates at the exon level and assigns unique and meaningful identifiers to each gene. 相似文献
180.
Chalifa-Caspi V Shmueli O Benjamin-Rodrig H Rosen N Shmoish M Yanai I Ophir R Kats P Safran M Lancet D 《Briefings in bioinformatics》2003,4(4):349-360
The interpretation of microarray expression results often includes extensive efforts to identify and annotate the gene representatives immobilised on the arrays. In this paper we describe the usage of our automatic GeneAnnot system, which links between Affymetrix arrays and the rich human gene annotations available in GeneCards. We explain GeneCards search options and results display; elaborate on the presentation of expression information in GeneCards, including both our whole-genome GeneNote project and external expression resources; describe the various parameters and displays used by GeneAnnot to assess the annotation quality and probeset specificity; and show how to search GeneAnnot and GeneNote websites directly. 相似文献