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排序方式: 共有1133条查询结果,搜索用时 31 毫秒
41.
Michael J. Breen Diarmuid M. Moran Wenzhe Liu Xiaoke Huang Calvin P. H. Vary Raymond C. Bergan 《PloS one》2013,8(8)
Mortality from prostate cancer (PCa) is due to the formation of metastatic disease. Understanding how that process is regulated is therefore critical. We previously demonstrated that endoglin, a type III transforming growth factor β (TGFβ) superfamily receptor, suppresses human PCa cell invasion and metastasis. Endoglin-mediated suppression of invasion was also shown by us to be dependent upon the type I TGFβ receptor, activin receptor-like kinase 2 (ALK2), and the downstream effector, Smad1. In this study we demonstrate for the first time that two type II TGFβ receptors are required for endoglin-mediated suppression of invasion: activin A receptor type IIA (ActRIIA) and bone morphogenetic protein receptor type II (BMPRII). Downstream signaling through these receptors is predominantly mediated by Smad1. ActRIIA stimulates Smad1 activation in a kinase-dependent manner, and this is required for suppression of invasion. In contrast BMPRII regulates Smad1 in a biphasic manner, promoting Smad1 signaling through its kinase domain but suppressing it through its cytoplasmic tail. BMPRII’s Smad1-regulatory effects are dependent upon its expression level. Further, its ability to suppress invasion is independent of either kinase function or tail domain. We demonstrate that ActRIIA and BMPRII physically interact, and that each also interacts with endoglin. The current findings demonstrate that both BMPRII and ActRIIA are necessary for endoglin-mediated suppression of human PCa cell invasion, that they have differential effects on Smad1 signaling, that they make separate contributions to regulation of invasion, and that they functionally and physically interact. 相似文献
42.
Cerutti Julia M. B. Burt April J. Haupt Philip Bunbury Nancy Mumby Peter J. Schaepman-Strub Gabriela 《Coral reefs (Online)》2020,39(1):15-26
Coral Reefs - The third global bleaching event caused prolonged elevated sea surface temperatures from 2014 to 2017 that heavily impacted coral reefs worldwide. This study determines changes in... 相似文献
43.
April M. Schueths 《Ethnic and racial studies》2013,36(13):2438-2456
This article expands the theoretical debate on racist nativism and the specific impact that it has on the experiences of interracial mixed-status couples in the USA. In-depth interviews suggest that the costs of racist nativist microaggressions and macroaggressions are experienced differently, depending on the social status of each member of the couple. Microaggressions target Latinos/as, while racial profiling, a macroaggression, is mainly experienced by Latino men; however, in both cases their white partners also experience rebound racism on behalf of their partners. White women partnered with Latinos experience the greatest rebound effects of racist nativism. Larger macro-policies create a precarious position for couples; this leads them to make calculated legal risks to sustain their families and ultimately constrains their freedoms. 相似文献
44.
Bryan D. Yestrepsky Yuanxi Xu Meghan E. Breen Xiaoqin Li Walajapet G. Rajeswaran Jenny G. Ryu Roderick J. Sorenson Yasuhiro Tsume Michael W. Wilson Wenpeng Zhang Duxin Sun Hongmin Sun Scott D. Larsen 《Bioorganic & medicinal chemistry》2013,21(7):1880-1897
Resistance to antibiotics is an increasingly dire threat to human health that warrants the development of new modes of treating infection. We recently identified 1 (CCG-2979) as an inhibitor of the expression of streptokinase, a critical virulence factor in Group A Streptococcus that endows blood-borne bacteria with fibrinolytic capabilities. In this report, we describe the synthesis and biological evaluation of a series of novel 5,6-dihydrobenzo[h]quinazolin-4(3H)-one analogs of 1 undertaken with the goal of improving the modest potency of the lead. In addition to achieving an over 35-fold increase in potency, we identified structural modifications that improve the solubility and metabolic stability of the scaffold. The efficacy of two new compounds 12c (CCG-203592) and 12k (CCG-205363) against biofilm formation in Staphylococcus aureus represents a promising additional mode of action for this novel class of compounds. 相似文献
45.
Michael Breen Aitor Nogales Steven F. Baker Daniel R. Perez Luis Martínez-Sobrido 《PloS one》2016,11(1)
Influenza A and B viruses (IAV and IBV, respectively) cause annual seasonal human respiratory disease epidemics. In addition, IAVs have been implicated in occasional pandemics with inordinate health and economic consequences. Studying influenza viruses in vitro or in vivo requires the use of laborious secondary methodologies to identify infected cells. To circumvent this requirement, replication-competent infectious influenza viruses expressing an easily traceable fluorescent reporter protein can be used. Timer is a fluorescent protein that undergoes a time-dependent color emission conversion from green to red. The rate of spectral change is independent of Timer protein concentration and can be used to chronologically measure the duration of its expression. Here, we describe the generation of replication-competent IAV and IBV where the viral non-structural protein 1 (NS1) was fused to the fluorescent dynamic Timer protein. Timer-expressing IAV and IBV displayed similar plaque phenotypes and growth kinetics to wild-type viruses in tissue culture. Within infected cells, Timer’s spectral shift can be used to measure the rate and cell-to-cell spread of infection using fluorescent microscopy, plate readers, or flow cytometry. The progression of Timer-expressing IAV infection was also evaluated in a mouse model, demonstrating the feasibility to characterize IAV cell-to-cell infections in vivo. By providing the ability to chronologically track viral spread, Timer-expressing influenza viruses are an excellent option to evaluate the in vitro and in vivo dynamics of viral infection. 相似文献
46.
Click chemistries have been investigated for use in numerous biomaterials applications, including drug delivery, tissue engineering, and cell culture. In particular, light-mediated click reactions, such as photoinitiated thiol−ene and thiol−yne reactions, afford spatiotemporal control over material properties and allow the design of systems with a high degree of user-directed property control. Fabrication and modification of hydrogel-based biomaterials using the precision afforded by light and the versatility offered by these thiol−X photoclick chemistries are of growing interest, particularly for the culture of cells within well-defined, biomimetic microenvironments. Here, we describe methods for the photoencapsulation of cells and subsequent photopatterning of biochemical cues within hydrogel matrices using versatile and modular building blocks polymerized by a thiol−ene photoclick reaction. Specifically, an approach is presented for constructing hydrogels from allyloxycarbonyl (Alloc)-functionalized peptide crosslinks and pendant peptide moieties and thiol-functionalized poly(ethylene glycol) (PEG) that rapidly polymerize in the presence of lithium acylphosphinate photoinitiator and cytocompatible doses of long wavelength ultraviolet (UV) light. Facile techniques to visualize photopatterning and quantify the concentration of peptides added are described. Additionally, methods are established for encapsulating cells, specifically human mesenchymal stem cells, and determining their viability and activity. While the formation and initial patterning of thiol-alloc hydrogels are shown here, these techniques broadly may be applied to a number of other light and radical-initiated material systems (e.g., thiol-norbornene, thiol-acrylate) to generate patterned substrates. 相似文献
47.
Abigail H. Davies Joanna McGlashan Mareike G. Posner April K. Roberts Clifford C. Shone K. Ravi Acharya 《Biochemistry and Biophysics Reports》2016
Clostridium difficile binary toxin (CDT) is an ADP-ribosyltransferase which is linked to enhanced pathogenesis of C. difficile strains. CDT has dual function: domain a (CDTa) catalyses the ADP-ribosylation of actin (enzymatic component), whereas domain b (CDTb) transports CDTa into the cytosol (transport component). Understanding the molecular mechanism of CDT is necessary to assess its role in C. difficile infection. Identifying amino acids that are essential to CDTa function may aid drug inhibitor design to control the severity of C. difficile infections. Here we report mutations of key catalytic residues within CDTa and their effect on CDT cytotoxicity. Rather than an all-or-nothing response, activity of CDTa mutants vary with the type of amino acid substitution; S345A retains cytotoxicity whereas S345Y was sufficient to render CDT non-cytotoxic. Thus CDTa cytotoxicity levels are directly linked to ADP-ribosyltransferase activity. 相似文献
48.
49.
DnaJ/Hsc70 chaperone complexes control the extracellular release of neurodegenerative‐associated proteins
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Dali Zheng Dale Chaput April Darling Justin H Trotter Andrew R Stothert Bryce A Nordhues April Lussier Jeremy Baker Lindsey Shelton Mahnoor Kahn Laura J Blair Stanley M Stevens Jr Chad A Dickey 《The EMBO journal》2016,35(14):1537-1549
It is now known that proteins associated with neurodegenerative disease can spread throughout the brain in a prionlike manner. However, the mechanisms regulating the trans‐synaptic spread propagation, including the neuronal release of these proteins, remain unknown. The interaction of neurodegenerative disease‐associated proteins with the molecular chaperone Hsc70 is well known, and we hypothesized that much like disaggregation, refolding, degradation, and even normal function, Hsc70 may dictate the extracellular fate of these proteins. Here, we show that several proteins, including TDP‐43, α‐synuclein, and the microtubule‐associated protein tau, can be driven out of the cell by an Hsc70 co‐chaperone, DnaJC5. In fact, DnaJC5 overexpression induced tau release in cells, neurons, and brain tissue, but only when activity of the chaperone Hsc70 was intact and when tau was able to associate with this chaperone. Moreover, release of tau from neurons was reduced in mice lacking the DnaJC5 gene and when the complement of DnaJs in the cell was altered. These results demonstrate that the dynamics of DnaJ/Hsc70 complexes are critically involved in the release of neurodegenerative disease proteins. 相似文献
50.
Joseph?Hatem April?M.?Schrank-Hacker Christopher?D.?Watt Jennifer?J.?D.?Morrissette Adam?I.?Rubin Ellen?J.?Kim Sunita?D.?Nasta Mariusz?A.?Wasik Agata?M.?BoguszEmail author 《Diagnostic pathology》2016,11(1):137