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排序方式: 共有139条查询结果,搜索用时 15 毫秒
81.
82.
Marcus A. Begley April L. Solon Elizabeth Mae Davis Michael Grant Sherrill Ryoma Ohi Mary Williard Elting 《Molecular biology of the cell》2021,32(22)
The mitotic spindle, a self-constructed microtubule-based machine, segregates chromosomes during cell division. In mammalian cells, microtubule bundles called kinetochore fibers (k-fibers) connect chromosomes to the spindle poles. Chromosome segregation thus depends on the mechanical integrity of k-fibers. Here we investigate the physical and molecular basis of k-fiber bundle cohesion. We detach k-fibers from poles by laser ablation-based cutting, thus revealing the contribution of pole-localized forces to k-fiber cohesion. We then measure the physical response of the remaining kinetochore-bound segments of the k-fibers. We observe that microtubules within ablated k-fibers often splay apart from their minus-ends. Furthermore, we find that minus-end clustering forces induced by ablation seem at least partially responsible for k-fiber splaying. We also investigate the role of the k-fiber-binding kinesin-12 Kif15. We find that pharmacological inhibition of Kif15-microtubule binding reduces the mechanical integrity of k-fibers. In contrast, inhibition of its motor activity but not its microtubule binding ability, i.e., locking Kif15 into a rigor state, does not greatly affect splaying. Altogether, the data suggest that forces holding k-fibers together are of similar magnitude to other spindle forces, and that Kif15, acting as a microtubule cross-linker, helps fortify and repair k-fibers. This feature of Kif15 may help support robust k-fiber function and prevent chromosome segregation errors. 相似文献
83.
84.
Stokes KL Chi MH Sakamoto K Newcomb DC Currier MG Huckabee MM Lee S Goleniewska K Pretto C Williams JV Hotard A Sherrill TP Peebles RS Moore ML 《Journal of virology》2011,85(12):5782-5793
Airway mucus is a hallmark of respiratory syncytial virus (RSV) lower respiratory tract illness. Laboratory RSV strains differentially induce airway mucus production in mice. Here, we tested the hypothesis that RSV strains differ in pathogenesis by screening six low-passage RSV clinical isolates for mucogenicity and virulence in BALB/cJ mice. The RSV clinical isolates induced variable disease severity, lung interleukin-13 (IL-13) levels, and gob-5 levels in BALB/cJ mice. We chose two of these clinical isolates for further study. Infection of BALB/cJ mice with RSV A2001/2-20 (2-20) resulted in greater disease severity, higher lung IL-13 levels, and higher lung gob-5 levels than infection with RSV strains A2, line 19, Long, and A2001/3-12 (3-12). Like the line 19 RSV strain, the 2-20 clinical isolate induced airway mucin expression in BALB/cJ mice. The 2-20 and 3-12 RSV clinical isolates had higher lung viral loads than laboratory RSV strains at 1 day postinfection (p.i.). This increased viral load correlated with higher viral antigen levels in the bronchiolar epithelium and greater histopathologic changes at 1 day p.i. The A2 RSV strain had the highest peak viral load at day 4 p.i. RSV 2-20 infection caused epithelial desquamation, bronchiolitis, airway hyperresponsiveness, and increased breathing effort in BALB/cJ mice. We found that RSV clinical isolates induce variable pathogenesis in mice, and we established a mouse model of clinical isolate strain-dependent RSV pathogenesis that recapitulates key features of RSV disease. 相似文献
85.
Fred G. Silva Karen Sherrill Sandra Spurgeon Thomas C. Südhof Dennis K. Stone 《Differentiation; research in biological diversity》1987,33(3):175-183
Abstract. Calelectrins are a family of antigenically related Ca2+ -binding proteins that have only recently been described. They have the important property of binding to membranes only in the presence of Ca2+ . We systematically studied the tissue localization of one calelectrin, the 32.5-kilodalton species, in rats using immunocytochemistry. We found that high levels were exclusively present in the epithelial cells of bile and pancreatic ducts, renal collecting ducts, bronchial epithelia, and brain ependyma. In all of these organs, the other cells were not immunoreactive. In addition, strong immunoreactivity was found in the intercalated disks of myocardial cells, and mild immunoreactivity was observed in several endocrine tissues. In contrast, the cellular distribution of the 67-kilodalton calelectrin was more diffuse, involving most parenchymal cells in addition to the already-mentioned cells. Due to the presence of high levels of 32.5-kilodalton calelectrin in some cell types, this protein may be used as a histochemical marker for differentiated ductal epithelial cells, some specialized epithelia, myocardial cells, and Paneth cells. 相似文献
86.
Anderson MO Sherrill J Madrid PB Liou AP Weisman JL DeRisi JL Guy RK 《Bioorganic & medicinal chemistry》2006,14(2):334-343
A parallel synthetic strategy to the 9-aminoacridine scaffold of the classical anti-malarial drug quinacrine (2) is presented. The method features a new route to 9-chloroacridines that utilizes triflates of salicylic acid derivatives, which are commercially available in a variety of substitution patterns. The route allows ready variation of the two diversity elements present in this class of molecules: the tricyclic aromatic heterocyclic core, and the disubstituted diamine sidechain. In this study, a library of 175 compounds was designed, although only 93 of the final products had purities acceptable for screening. Impurity was generally due to incomplete removal of 9-acridones (18), a degradation product of the 9-chloroacridine synthetic intermediates. The library was screened against two strains of Plasmodium falciparum, including a model of the drug-resistant parasite, and six novel compounds were found to have IC(50) values in the low nanomolar range. 相似文献
87.
Peter F. Galbreath Nathan D. Adams Lee. W. Sherrill III Thomas H. Martin 《Environmental Biology of Fishes》2006,75(2):183-193
Synopsis An effect of ploidy on thermal tolerance in juvenile trout was assessed in a series of tests comparing time to chronic lethal
maximum (CLMax). Diploid and triploid fish were produced from a common spawn for three different groups each of brook trout
Salvelinus fontinalis and of rainbow trout Oncorhynchus mykiss. One or two CLMax tests were performed per group, on between 15 and 50 individuals per ploidy within groups. The tests involved
exposure of fish to a progressive 2°C day−1 water temperature increase and recording of the time at which each individual fish reached loss of equilibrium (LE). The
time to LE data were rank transformed and analyzed as a randomized complete block design. Although relative performance varied
among trials, the analysis indicated overall differences due to ploidy were small and nonsignificant among both brook trout
and rainbow trout. Size proved to be significantly correlated with time to LE in the brook trout trials, but not in the rainbow
trout trials. Two of the six groups included a large proportion of fish which had received a heat shock following fertilization,
but were not successfully triploidized. In both cases, thermal tolerance of the heat-shocked diploids was similar to that
of the non-heat shocked control diploids, indicating no persistent effect of the heat shock on thermal tolerance. 相似文献
88.
Taylor PB Stewart FP Dunnington DJ Quinn ST Schulz CK Vaidya KS Kurali E Lane TR Xiong WC Sherrill TP Snider JS Terpstra ND Hertzberg RP 《Journal of biomolecular screening》2000,5(4):213-226
The transition from manual to robotic high throughput screening (HTS) in the last few years has made it feasible to screen hundreds of thousands of chemical entities against a biological target in less than a month. This rate of HTS has increased the visibility of bottlenecks, one of which is assay optimization. In many organizations, experimental methods are generated by therapeutic teams associated with specific targets and passed on to the HTS group. The resulting assays frequently need to be further optimized to withstand the rigors and time frames inherent in robotic handling. Issues such as protein aggregation, ligand instability, and cellular viability are common variables in the optimization process. The availability of robotics capable of performing rapid random access tasks has made it possible to design optimization experiments that would be either very difficult or impossible for a person to carry out. Our approach to reducing the assay optimization bottleneck has been to unify the highly specific fields of statistics, biochemistry, and robotics. The product of these endeavors is a process we have named automated assay optimization (AAO). This has enabled us to determine final optimized assay conditions, which are often a composite of variables that we would not have arrived at by examining each variable independently. We have applied this approach to both radioligand binding and enzymatic assays and have realized benefits in both time and performance that we would not have predicted a priori. The fully developed AAO process encompasses the ability to download information to a robot and have liquid handling methods automatically created. This evolution in smart robotics has proven to be an invaluable tool for maintaining high-quality data in the context of increasing HTS demands. 相似文献
89.
Replicon vectors derived from Sindbis virus and Semliki forest virus that establish persistent replication in host cells 总被引:1,自引:0,他引:1 下载免费PDF全文
Perri S Driver DA Gardner JP Sherrill S Belli BA Dubensky TW Polo JM 《Journal of virology》2000,74(20):9802-9807
Alphavirus replicon vectors are well suited for applications where transient, high-level expression of a heterologous gene is required. Replicon vector expression in cells leads to inhibition of host macromolecular synthesis, culminating in eventual cell death by an apoptotic mechanism. For many applications, including gene expression studies in cultured cells, a longer duration of transgene expression without resulting cytopathic effects is useful. Recently, noncytopathic Sindbis virus (SIN) variants were isolated in BHK cells, and the mutations responsible were mapped to the protease domain of nonstructural protein 2 (nsP2). We report here the isolation of additional variants of both SIN and Semliki Forest virus (SFV) replicons encoding the neomycin resistance gene that can establish persistent replication in BHK cells. The SIN and SFV variant replicons resulted from previously undescribed mutations within one of three discrete regions of the nsP2 gene. Differences among the panel of variants were observed in processing of the nonstructural polyprotein and in the ratios of subgenomic to genomic RNAs. Importantly, high-level expression of a heterologous gene was retained with most replicons. Finally, in contrast to previous studies, efficient packaging was obtained with several of the variant replicons. This work expands the utility of noncytopathic replicons and the understanding of how alphavirus replicons establish persistent replication in cultured cells. 相似文献
90.