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141.
ARTEMIS stabilizes the genome and modulates proliferative responses in multipotent mesenchymal cells
Background
Unrepaired DNA double-stranded breaks (DSBs) cause chromosomal rearrangements, loss of genetic information, neoplastic transformation or cell death. The nonhomologous end joining (NHEJ) pathway, catalyzing sequence-independent direct rejoining of DSBs, is a crucial mechanism for repairing both stochastically occurring and developmentally programmed DSBs. In lymphocytes, NHEJ is critical for both development and genome stability. NHEJ defects lead to severe combined immunodeficiency (SCID) and lymphoid cancer predisposition in both mice and humans. While NHEJ has been thoroughly investigated in lymphocytes, the importance of NHEJ in other cell types, especially with regard to tumor suppression, is less well documented. We previously reported evidence that the NHEJ pathway functions to suppress a range of nonlymphoid tumor types, including various classes of sarcomas, by unknown mechanisms. 相似文献142.
Zogopoulos G Ha KC Naqib F Moore S Kim H Montpetit A Robidoux F Laflamme P Cotterchio M Greenwood C Scherer SW Zanke B Hudson TJ Bader GD Gallinger S 《Human genetics》2007,122(3-4):345-353
Genomic copy number variation (CNV) is a recently identified form of global genetic variation in the human genome. The Affymetrix
GeneChip 100 and 500 K SNP genotyping platforms were used to perform a large-scale population-based study of CNV frequency.
We constructed a genomic map of 578 CNV regions, covering approximately 220 Mb (7.3%) of the human genome, identifying 183
previously unknown intervals. Copy number changes were observed to occur infrequently (<1%) in the majority (>93%) of these
genomic regions, but encompass hundreds of genes and disease loci. This North American population-based map will be a useful
resource for future genetic studies.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
143.
Fossilized flowers of ericalean affinity are reported from the Turanian (ca. 90 MYBP, million years before present) of New Jersey. The fossils are remarkably well preserved and three-dimensional, and are the oldest known floral remains of Ericales. The series of fossil flower buds, floral fragments, and fruits are not identical to any modern genus of Ericales. The inverted U-shaped anthers with pseudoterminal awns, and the fluted syncarpous ovary of the fossils suggest affinities with basal Ericaceae, probably near extant Enkianthus, a taxon that also shares monadinous pollen with the fossil. Pollen grains were observed clumped on a stigma in one of the fossil flowers. Fossilized acid-resistant strands having characteristics, including similar diameter and sculpture pattern, in common with the muri connect pollen grains and, with scanning electron microscopy, appear continuous with the tectum, supporting the interpretation that they are viscin threads. These are the oldest reported fossilized viscin threads, and the only fossilized viscin threads found in situ in flowers. In modern Ericales and Onagraceae, the presence of viscin threads is associated with highly specific plant-pollinator relationships, raising the possibility that such specific pollinator-plant relationships had developed by the mid-Cretaceous. This is consistent with floral characters in these ericalean fossils, the presence of advanced meliponine bees in slightly younger sediments from the same region, and with the morphology and affinities of other fossil flowers from the same sediments. 相似文献
144.
Adnan M. M. Mjalli Kevin T. Chapman Malcolm MacCoss Nancy A. Thornberry 《Bioorganic & medicinal chemistry letters》1993,3(12):2689-2692
Phenylalkyl ketones are potent reversible inhibitors of interleukin-1β converting enzyme (ICE). The extended alkyl chain ketones AcTyrValAlaAspCO(CH2)nPh display increased potency over the simple aryl ketone. In particular, the tetrapeptide AcTyrValAlaAspCOPh has a Ki of 10μM while AcTyrValAlaAspCO(CH2)5Ph has a Ki of 18.5nM. 相似文献
145.
Lindström Irene Bontell Neil Hall Kevin E Ashelford JP Dubey Jon P Boyle Johan Lindh Judith E Smith 《Genome biology》2009,10(5):R53-17
Background
Toxoplasma gondii is a zoonotic parasite of global importance. In common with many protozoan parasites it has the capacity for sexual recombination, but current evidence suggests this is rarely employed. The global population structure is dominated by a small number of clonal genotypes, which exhibit biallelic variation and limited intralineage divergence. Little is known of the genotypes present in Africa despite the importance of AIDS-associated toxoplasmosis. 相似文献146.
147.
Currie KP 《Channels (Austin, Tex.)》2010,4(6):497-509
Voltage-gated Ca(2+) channels translate the electrical inputs of excitable cells into biochemical outputs by controlling influx of the ubiquitous second messenger Ca(2+) . As such the channels play pivotal roles in many cellular functions including the triggering of neurotransmitter and hormone release by CaV2.1 (P/Q-type) and CaV2.2 (N-type) channels. It is well established that G protein coupled receptors (GPCRs) orchestrate precise regulation neurotransmitter and hormone release through inhibition of CaV2 channels. Although the GPCRs recruit a number of different pathways, perhaps the most prominent, and certainly most studied among these is the so-called voltage-dependent inhibition mediated by direct binding of Gβγ to the α1 subunit of CaV2 channels. This article will review the basics of Ca(2+) -channels and G protein signaling, and the functional impact of this now classical inhibitory mechanism on channel function. It will also provide an update on more recent developments in the field, both related to functional effects and crosstalk with other signaling pathways, and advances made toward understanding the molecular interactions that underlie binding of Gβγ to the channel and the voltage-dependence that is a signature characteristic of this mechanism. 相似文献
148.
Gabriel O. Reznik Prashanth Vishwanath Michelle A. Pynn Joy M. Sitnik Jeffrey J. Todd Jun Wu Yan Jiang Brendan G. Keenan Andrew B. Castle Richard F. Haskell Temple F. Smith Ponisseril Somasundaran Kevin A. Jarrell 《Applied microbiology and biotechnology》2010,86(5):1387-1397
Surfactants find wide commercial use as foaming agents, emulsifiers, and dispersants. Currently, surfactants are produced from petroleum, or from seed oils such as palm or coconut oil. Due to concerns with CO2 emissions and the need to protect rainforests, there is a growing necessity to manufacture these chemicals using sustainable resources In this report, we describe the engineering of a native nonribosomal peptide synthetase pathway (i.e., surfactin synthetase), to generate a Bacillus strain that synthesizes a highly water-soluble acyl amino acid surfactant, rather than the water insoluble lipopeptide surfactin. This novel product has a lower CMC and higher water solubility than myristoyl glutamate, a commercial surfactant. This surfactant is produced by fermentation of cellulosic carbohydrate as feedstock. This method of surfactant production provides an approach to sustainable manufacturing of new surfactants. 相似文献
149.
Molecular chaperones monitor protein homeostasis and defend against the misfolding and aggregation of proteins that is associated with protein conformational disorders. In these diseases, a variety of different aggregate structures can form. These are called prion strains, or variants, in prion diseases, and cause variation in disease pathogenesis. Here, we use variants of the yeast prions [RNQ+] and [PSI+] to explore the interactions of chaperones with distinct aggregate structures. We found that prion variants show striking variation in their relationship with Hsp40s. Specifically, the yeast Hsp40 Sis1 and its human orthologue Hdj1 had differential capacities to process prion variants, suggesting that Hsp40 selectivity has likely changed through evolution. We further show that such selectivity involves different domains of Sis1, with some prion conformers having a greater dependence on particular Hsp40 domains. Moreover, [PSI+] variants were more sensitive to certain alterations in Hsp70 activity as compared to [RNQ+] variants. Collectively, our data indicate that distinct chaperone machinery is required, or has differential capacity, to process different aggregate structures. Elucidating the intricacies of chaperone‐client interactions, and how these are altered by particular client structures, will be crucial to understanding how this system can go awry in disease and contribute to pathological variation. 相似文献
150.