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111.
Rotem Tidhar Kacee Sims Eden Rosenfeld-Gur Walter Shaw Anthony H. Futerman 《Journal of lipid research》2015,56(1):193-199
Ceramides are synthesized by six mammalian ceramide synthases (CerSs), each of which uses fatty acyl-CoAs of different chain lengths for N-acylation of the sphingoid long-chain base. We now describe a rapid and reliable CerS assay that uses a fluorescent N-[6-[(7-nitrobenzo-2-oxa-1,3-diazol-4-yl) (NBD) sphinganine substrate followed by separation of the NBD-lipid substrate and products using solid phase extraction (SPE) C18 chromatography. SPE chromatography is a quick and reliable alternative to TLC, and moreover, there is no degradation of either NBD-sphinganine or NBD-ceramide. We have optimized the assay for use with minimal amounts of protein in a minimal volume. This assay will prove useful for the analysis of CerS activity, which is of particular importance in light of the growing involvement of CerS in cell regulation and in the pathology of human diseases. 相似文献
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114.
Simpson SD Jennings S Johnson MP Blanchard JL Schön PJ Sims DW Genner MJ 《Current biology : CB》2011,21(18):1565-1570
Climate change affects marine biological processes from genetic to ecosystem levels [1-3]. Recent warming in the northeast Atlantic [4, 5] has caused distributional shifts in some fish species along latitudinal and depth gradients [6,?7], but such changes, as predicted by climate envelope models [8], may often be prevented because population movement requires availability of suitable habitat. We assessed the full impacts of warming on the commercially important European continental shelf fish assemblage using a data-driven Eulerian (grid-based) approach that accommodates spatial heterogeneity in ecological and environmental conditions. We analyzed local associations of species abundance and community diversity with climatic variables, assessing trends in 172 cells from records of >100 million individuals sampled over 1.2 million km(2) from 1980-2008. We demonstrate responses to warming in 72% of common species, with three times more species increasing in abundance than declining, and find these trends reflected in international commercial landings. Profound reorganization of the relative abundance of species in local communities occurred despite decadal stability in the presence-absence of species. Our analysis highlights the importance of focusing on changes in species abundance in established local communities to assess the full consequences of climate change for commercial fisheries and food security. 相似文献
115.
Garabed Gary Demerjian Anothony Benjamin Sims Brendan Curran Stack 《Bioinformation》2011,5(7):282-284
The temporomandibular joint (TMJ) articulates the mandible with the maxilla. Temporomandibular joint disorders (TMD) are dysfunctions of this joint,
which range from acute to chronic inflammation, trauma and dislocations, developmental anomalies and neoplasia. TMD manifest as signs and symptoms
that involve the surrounding muscles, ligaments, bones, synovial capsule, connective tissue, teeth and innervations proximal and distal to this joint. TMD
induce proximal and distal, chronic and acute, dull or intense pain and discomfort, muscle spasm, clicking/popping sounds upon opening and closing of
the mouth, and chewing or speaking difficulties. The trigeminal cranial nerve V, and its branches provide the primary sensory innervation to the TMJ. Our
clinical work suggests that the auriculotemporal (AT) nerve, a branch of the mandibular nerve, the largest of the three divisions of the trigeminal nerve,
plays a critical role in TMD sequelae. The AT nerve provides the somatosensory fibers that supply the joint, the middle ear, and the temporal region. By
projecting fibers toward the otic ganglion, the AT nerve establishes an important bridge to the sympathetic system. As it courses posteriorly to the
condylar head of the TMJ, compression, injury or irritation of the AT nerve can lead to significant neurologic and neuro-muscular disorders, including
Tourette''s syndrome,Torticolli, gait or balance disorders and Parkinson’s disease. Here, we propose that a proteomic signature of TMD can be obtained by
assessing certain biomarkers in local (e.g., synovial fluid at the joint) and distal body fluids (e.g., saliva, cerebrospinal fluid), which can aid TMD
diagnosis and prognosis. 相似文献
116.
Feeley EM Sims JS John SP Chin CR Pertel T Chen LM Gaiha GD Ryan BJ Donis RO Elledge SJ Brass AL 《PLoS pathogens》2011,7(10):e1002337
To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats. 相似文献
117.
Andrew M. Griffiths David W. Sims Andrew Johnson Arve Lynghammar Matthew McHugh Torkild Bakken Martin J. Genner 《Conservation Genetics》2011,12(2):577-582
Sequencing of a partial region of the mitochondrial control region has revealed no shared haplotypes between longnose skate (Dipturus oxyrinchus L.) sampled in the north-eastern Atlantic (Norway and Rockall) and those sampled in the Mediterranean (Mallorca). Bayesian estimation of the migration rate suggests little, if any, gene flow occurs between the regions and that the populations separated 20,000?years ago. These conclusions provide a genetic basis for long-standing observations, based on egg capsule and adult size, that longnose skate in the Mediterranean may be genetically isolated from other stocks. This result has important conservation implications for the threatened longnose skate. 相似文献
118.
During chromosome duplication, it is essential to replicate not only the DNA sequence, but also the complex nucleoprotein structures of chromatin. Pericentric heterochromatin is critical for silencing repetitive elements and plays an essential structural role during mitosis. However, relatively little is understood about its assembly and maintenance during replication. The Mi2/NuRD chromatin remodeling complex tightly associates with actively replicating pericentric heterochromatin, suggesting a role in its assembly. Here we demonstrate that depletion of the catalytic ATPase subunit CHD4/Mi-2β in cells with a dampened DNA damage response results in a slow-growth phenotype characterized by delayed progression through S phase. Furthermore, we observe defects in pericentric heterochromatin maintenance and assembly. Our data suggest that chromatin assembly defects are sensed by an ATM-dependent intra-S phase chromatin quality checkpoint, resulting in a temporal block to the transition from early to late S phase. These findings implicate Mi-2β in the maintenance of chromatin structure and proper cell cycle progression. 相似文献
119.
Regulation of intracellular Ca2+ release in corpus cavernosum smooth muscle: synergism between nitric oxide and cGMP 总被引:1,自引:0,他引:1
Williams BA Liu C Deyoung L Brock GB Sims SM 《American journal of physiology. Cell physiology》2005,288(3):C650-C658
Tonic contraction of corpus cavernosum smooth muscle cells (SMCs) maintains the flaccid state of the penis, and relaxation is initiated by nitric oxide (NO), leading to erection. Our aim was to investigate the effect of NO on the smooth muscle cellular response to adrenergic stimulation in corpus cavernosum. Fura-2 fluorescence was used to record intracellular Ca2+ concentration ([Ca2+]i) from freshly isolated SMCs from rat and human. Phenylephrine (PE) transiently elevated [Ca2+]i in the presence and absence of extracellular Ca2+, indicating release from intracellular stores. Whereas the NO donor S-nitroso-N-acetylpenicillamine (SNAP) with sildenafil citrate (SIL) caused no change in basal [Ca2+]i, the PE-induced rise of [Ca2+]i was reversibly inhibited by 27 ± 7% (n = 21, P < 0.005) in rat and by 55 ± 15% (n = 9, P < 0.01) in human SMCs. SNAP and SIL also reduced the contractile response to PE. To investigate the mechanism, we applied mediators alone or in combination. The soluble guanylyl cyclase inhibitor ODQ reduced the effect of SNAP and SIL. SIL, cGMP analogs, and NO donors without SIL did not reduce the PE-induced rise of [Ca2+]i. However, the combination of 8-bromo-cGMP with SNAP reduced the Ca2+ peak by 42 ± 9% (n = 22, P < 0.01). Our results demonstrate that NO and cGMP act synergistically to reduce Ca2+ release from intracellular stores. Reduction of intracellular Ca2+ release may contribute to relaxation of the corpus cavernosum, leading to erection. calcium stores; nitric oxide; sildenafil citrate; inositol 1,4,5-trisphosphate receptor 相似文献
120.
Sims AH Gent ME Lanthaler K Dunn-Coleman NS Oliver SG Robson GD 《Applied and environmental microbiology》2005,71(5):2737-2747
Filamentous fungi have a high capacity for producing large amounts of secreted proteins, a property that has been exploited for commercial production of recombinant proteins. However, the secretory pathway, which is key to the production of extracellular proteins, is rather poorly characterized in filamentous fungi compared to yeast. We report the effects of recombinant protein secretion on gene expression levels in Aspergillus nidulans by directly comparing a bovine chymosin-producing strain with its parental wild-type strain in continuous culture by using expressed sequence tag microarrays. This approach demonstrated more subtle and specific changes in gene expression than those observed when mimicking the effects of protein overproduction by using a secretion blocker. The impact of overexpressing a secreted recombinant protein more closely resembles the unfolded-protein response in vivo. 相似文献