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排序方式: 共有241条查询结果,搜索用时 15 毫秒
231.
Eirini Christodoulou Mamunur Rashid Clare Pacini Alastair Droop Holly Robertson Tim van Groningen Amina F. A. S. Teunisse Francesco Iorio Aart G. Jochemsen David J. Adams Remco van Doorn 《Pigment cell & melanoma research》2021,34(1):122-131
Targeting the MAPK signaling pathway has transformed the treatment of metastatic melanoma. CRISPR‐Cas9 genetic screens provide a genome‐wide approach to uncover novel genetic dependencies that might serve as therapeutic targets. Here, we analyzed recently reported CRISPR‐Cas9 screens comparing data from 28 melanoma cell lines and 313 cell lines of other tumor types in order to identify fitness genes related to melanoma. We found an average of 1,494 fitness genes in each melanoma cell line. We identified 33 genes, inactivation of which specifically reduced the fitness of melanoma. This set of tumor type‐specific genes includes established melanoma fitness genes as well as many genes that have not previously been associated with melanoma growth. Several genes encode proteins that can be targeted using available inhibitors. We verified that genetic inactivation of DUSP4 and PPP2R2A reduces the proliferation of melanoma cells. DUSP4 encodes an inhibitor of ERK, suggesting that further activation of MAPK signaling activity through its loss is selectively deleterious to melanoma cells. Collectively, these data present a resource of genetic dependencies in melanoma that may be explored as potential therapeutic targets. 相似文献
232.
Gaudeline Rémillard-Labrosse Constantina Mihai Johanne Duron Ginette Guay Roger Lippé 《Traffic (Copenhagen, Denmark)》2009,10(8):1074-1083
The biosynthetic pathway carries cargos from the endoplasmic reticulum (ER) to the trans Golgi network (TGN) via a typical passage through the Golgi. Interestingly, large particles such as procollagen, chylomicrons and some viruses all reach the TGN by atypical routes. Given this dichotomy, we anticipated that such cargos might rely on non-classical machineries downstream of the TGN. Using Herpes simplex virus type 1 (HSV-1) as a model and a synchronized infection protocol that focuses on TGN to plasma membrane transport, the present study revealed the surprising implication of the cellular serine-threonine protein kinase D in HSV-1 egress. These findings, confirmed by a variety of complementary means [pharmacological inhibitors, dominant negative mutant, RNA interference and electron microscopy (EM)], identify one of possibly several cellular factors that modulate the egress of viruses transiting at the TGN. Moreover, the involvement of this kinase, previously known to regulate the transport of small basolateral cargos, highlights the trafficking of both small and exceptionally large entities by a common machinery downstream of the TGN, in sharp contrast to earlier steps of transport. Conceptually, this indicates the TGN is not only a sorting station from which cargos can depart towards different destinations but also a meeting point where conventional and unconventional routes can meet along the biosynthetic pathway. Lastly, given the apical release of HSV-1 in neurons, it opens up the possibility that this kinase might regulate some apical sorting. 相似文献
233.
C.I. Christodoulou P.A. Kaplanis V. Murray M.S. Pattichis C.S. Pattichis T. Kyriakides 《Biomedical signal processing and control》2012,7(3):265-269
In this work, multi-scale amplitude modulation–frequency modulation (AM–FM) features are extracted from surface electromyographic (SEMG) signals and they are used for the classification of neuromuscular disorders. The method is validated on SEMG signals recorded from a total of 40 subjects: 20 normal and 20 abnormal cases (11 myopathy, and 9 neuropathy cases), at 10%, 30%, 50%, 70% and 100% of maximum voluntary contraction (MVC), from the biceps brachii muscle. For the classification, three classifiers are used: (i) the statistical K-nearest neighbor (KNN), (ii) the self-organizing map (SOM) and (iii) the support vector machine (SVM). For all classifiers, the leave-one-out methodology is used to validate the classification of the SEMG signals into normal or abnormal (myopathy or neuropathy). A classification success rate of 78% for the AM–FM features and SVM models was achieved. These results also show that SEMG can be used as a non-invasive alternative to needle EMG for differentiating between normal and abnormal (myopathy, or neuropathy) cases. 相似文献
234.
Four major hemolymph polypeptides (ceratitins) with molecular weights between 8.1 X 10(4) and 8.7 X 10(4) daltons have been identified in the fat body of late Ceratitis capitata larvae. Total fat body RNA from late larvae was translated in reticulocyte lysate, and the predominant in vitro translation products were shown to be the ceratitin precursors. The biosynthesis of these proteins during postembryonic development was studied in both tissue culture and cell-free system. Comparison of the biosynthetic patterns obtained in the two systems suggests a linear relationship between messenger concentration and protein synthesis. Three of these polypeptides show a coordinate pattern of synthesis and are immunologically related. After pupation, all four ceratitins are reabsorbed by the fat body where they accumulate. 相似文献
235.
L K Keefer J L Flippen-Anderson C George A P Shanklin T M Dunams D Christodoulou J E Saavedra E S Sagan D S Bohle 《Nitric oxide》2001,5(4):377-394
Ions of structure X[N(O)NO]-, examples of which have seen increasing use as probes for studying the biology of nitric oxide (NO) over the past decade, have a varied chemical history spanning nearly two centuries. Nevertheless, they have not been widely appreciated for their physicochemical similarities. Here we begin a series of systematic inquiries into the fundamental chemistry of such compounds aimed at identifying both the characteristics that justify considering them as a group and the factors that contribute to observed differences in their physicochemical properties. In the present paper, X-ray structures in which X is SO3- (1), O- (2), Ph (3), and Et2N (5), as well as that of the gem-disubstituted carbon derivative CH2[N(O)NO]2-(2) (4), are compared. All their O-N-N-O systems are essentially planar, with cis oxygens and an N-N linkage exhibiting considerable double-bond character. The ultraviolet spectrum of the isolated chromophore consists of a relatively intense ( approximately 6-10 mM(-1) x cm(-1) per [N(O)NO]- group) absorption at 248-250 nm (for 2 and 5) that is red shifted by through-space Stark interactions (e.g., by approximately 10 nm in 1 and 4) as well as by conjugative interaction with X (lambda(max) = 284 nm for 3). Infrared and Raman spectra for the widely used pharmacological probe 5 were determined, with analysis of vibrational modes being aided by comparison with the spectra of the [15N(O)15NO]- isotopomer and density functional theory calculations at the B3LYP/6-311++G** level. To address confusion that has arisen in the literature resulting from rather widespread use of differing trivial designations for this class of compounds, a unifying nomenclature system is recommended in which compounds containing the [N(O)NO]- moiety are named as diazeniumdiolates. It is hoped that these and other efforts to understand and predict the physicochemical similarities and differences among different members of the diazeniumdiolate class will aid in reaping their full potential in the area of rational drug design. 相似文献
236.
237.
A Simple Methodological Approach for Counting and Identifying Culturable Viruses Adsorbed to Cellulose Nitrate Membrane Filters 总被引:4,自引:4,他引:0
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Georgios T. Papageorgiou Laura Moc-Llivina Christina G. Christodoulou Francisco Lucena Dina Akkelidou Eleni Ioannou Juan Jofre 《Applied microbiology》2000,66(1):194-198
We identified conditions under which Buffalo green monkey cells grew on the surfaces of cellulose nitrate membrane filters in such a way that they covered the entire surface of each filter and penetrated through the pores. When such conditions were used, poliovirus that had previously been adsorbed on the membranes infected the cells and replicated. A plaque assay method and a quantal method (most probable number of cytopathic units) were used to detect and count the viruses adsorbed on the membrane filters. Polioviruses in aqueous suspensions were then concentrated by adsorption to cellulose membrane filters and were subsequently counted without elution, a step which is necessary when the commonly used methods are employed. The pore size of the membrane filter, the sample contents, and the sample volume were optimized for tap water, seawater, and a 0.25 M glycine buffer solution. The numbers of viruses recovered under the optimized conditions were more than 50% greater than the numbers counted by the standard plaque assay. When ceftazidime was added to the assay medium in addition to the antibiotics which are typically used, the method could be used to study natural samples with low and intermediate levels of microbial pollution without decontamination of the samples. This methodological approach also allowed plaque hybridization either directly on cellulose nitrate membranes or on Hybond N+ membranes after the preparations were transferred. 相似文献
238.
Signals obtained from serial dilutions of rat-derived Pneumocystis carinii DNA were used to assess the sensitivity of a 650-bp DNA probe which recognises both cystic and non-cystic forms. Enhanced chemiluminescence was selected as a non-radioactive detection method and signals could be semi-quantitated by scanning densitometry. This technique was used to examine the inhibitory effect of pentamidine in vitro indicating that DNA probes might be useful tools in the search for a novel therapeutic agent. 相似文献
239.
V. Christodoulou V.A. Bampidis A.G. Lymberopoulos P.H. Robinson K. Ploumi S. Belibasaki 《Animal Feed Science and Technology》2006,130(3-4):268-276
Seventy-two lactating Chios ewes were used in two experiments to determine effects of supplemental dietary biotin on productivity and milk composition. The first experiment started after weaning on day 42 postpartum, and lasted 20 weeks, while the second started on week 24 postpartum and lasted 12 weeks. In both experiments, ewes were allocated, after equal distribution relative to milk yield, body weight, time of lambing, and lactation number (i.e., two or three), into three groups of 24 ewes each, and were accommodated in three floor pens/groups of eight ewes/treatment. Ewes were fed one of three diets varying in supplemental biotin (BIOTIN0, no supplemental biotin; BIOTIN3, 3 mg supplemental biotin/ewe/day; BIOTIN5, 5 mg supplemental biotin/ewe/day) in each experiment. Milk, fat, protein, lactose and ash yield, and milk fat content increased linearly (P<0.012) with increased dietary biotin in both studies. Dietary biotin supplementation improved the productive performance of these lactating ewes at both an early and late stage of lactation. 相似文献
240.