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排序方式: 共有1614条查询结果,搜索用时 15 毫秒
1.
Corey R. Nelson Tyler Mrozowich Sean M. Park Simmone Dsouza Amy Henrickson Justin R. J. Vigar Hans-Joachim Wieden Raymond J. Owens Borries Demeler Trushar R. Patel 《International journal of molecular sciences》2021,22(1)
Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17135–555 interacting with and unwinding RVFV non-coding regions. 相似文献
2.
Ross C. Petersen Ian B. McCubbin John A. Ogren Elisabeth Andrews Douglas Lowenthal 《Aerosol science and technology》2019,53(6):712-727
The use of inlets for transferring aerosols from the environment to instrumentation can introduce uncertainty in the measurement of aerosol properties. Aerosol loss during this process is a non-negligible issue that may bias the subsequent measurements. These loss mechanisms include aspiration at the inlet head and deposition/evaporation/condensation during transport through the sampling lines. Coarse-mode aerosol is significantly impacted by the aspiration and inertial loss mechanisms within an inlet system. This work uses wind tunnel experiments to investigate aerosol losses through the Storm Peak Laboratory’s (SPL) new aerosol inlet system. The inlet is used extensively for both intensive field campaigns and long-term aerosol monitoring. The results of numerical simulations of the SPL aerosol inlet sampling efficiency are provided at several wind speeds, and experimental results demonstrate the system has a 50% cut off for the coarse-mode at an aerodynamic diameter of approximately 13?μm and wind speed of 0.5?m s?1. This investigation will lead to improved accuracy of in situ aerosol measurements at SPL and this system can be replicated at other atmospheric stations.
Copyright © 2019 American Association for Aerosol Research 相似文献
3.
Dr. Pui-Ying Lam Dr. Peter Kutchukian Rajan Anand Dr. Jason Imbriglio Dr. Christine Andrews Hugo Padilla Anita Vohra Sarah Lane Dann L. Parker Jr. Dr. Ivan Cornella Taracido Dr. Douglas G. Johns Dr. Manu Beerens Dr. Calum A. MacRae John P. Caldwell Dr. Steve Sorota Dr. Aarti Asnani Dr. Randall T. Peterson 《Chembiochem : a European journal of chemical biology》2020,21(13):1905-1910
Doxorubicin is a highly effective chemotherapy agent used to treat many common malignancies. However, its use is limited by cardiotoxicity, and cumulative doses exponentially increase the risk of heart failure. To identify novel heart failure treatment targets, a zebrafish model of doxorubicin-induced cardiomyopathy was previously established for small-molecule screening. Using this model, several small molecules that prevent doxorubicin-induced cardiotoxicity both in zebrafish and in mouse models have previously been identified. In this study, exploration of doxorubicin cardiotoxicity is expanded by screening 2271 small molecules from a proprietary, target-annotated tool compound collection. It is found that 120 small molecules can prevent doxorubicin-induced cardiotoxicity, including 7 highly effective compounds. Of these, all seven exhibited inhibitory activity towards cytochrome P450 family 1 (CYP1). These results are consistent with previous findings, in which visnagin, a CYP1 inhibitor, also prevents doxorubicin-induced cardiotoxicity. Importantly, genetic mutation of cyp1a protected zebrafish against doxorubicin-induced cardiotoxicity phenotypes. Together, these results provide strong evidence that CYP1 is an important contributor to doxorubicin-induced cardiotoxicity and highlight the CYP1 pathway as a candidate therapeutic target for clinical cardioprotection. 相似文献
4.
Corey Andrews Yiting Xu Michael Kirberger Jenny J. Yang 《International journal of molecular sciences》2021,22(1)
Calmodulin (CaM) is an important intracellular protein that binds Ca2+ and functions as a critical second messenger involved in numerous biological activities through extensive interactions with proteins and peptides. CaM’s ability to adapt to binding targets with different structures is related to the flexible central helix separating the N- and C-terminal lobes, which allows for conformational changes between extended and collapsed forms of the protein. CaM-binding targets are most often identified using prediction algorithms that utilize sequence and structural data to predict regions of peptides and proteins that can interact with CaM. In this review, we provide an overview of different CaM-binding proteins, the motifs through which they interact with CaM, and shared properties that make them good binding partners for CaM. Additionally, we discuss the historical and current methods for predicting CaM binding, and the similarities and differences between these methods and their relative success at prediction. As new CaM-binding proteins are identified and classified, we will gain a broader understanding of the biological processes regulated through changes in Ca2+ concentration through interactions with CaM. 相似文献
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Dr. Liam J. Stephens Dr. Aviva Levina Dr. Iman Trinh Dr. Victoria L. Blair Dr. Melissa V. Werrett Prof. Peter A. Lay Prof. Philip C. Andrews 《Chembiochem : a European journal of chemical biology》2020,21(8):1188-1200
RuII-arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new RuII-arene-thiocarboxylato dimers were synthesized and characterized. Three of the complexes ( 2 a , b and 5 ) showed promising antiproliferative activities in MDA-MB-231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous and noncancerous cell lines. Complex 5 showed moderate but remarkably selective activity in MDA-MB-231 cells (IC50=39±4 μm Ru). Real-time proliferation studies showed that 5 induced apoptosis in MDA-MB-231 cells but had no effect in A549 (human lung cancer, epithelial) cells. By contrast, 2 a and b showed moderate antiproliferative activity, but no apoptosis, in either cell line. Selective cytotoxicity of 5 in aggressive, mesenchymal-like MDA-MB-231 cells over many common epithelial cancer cell lines (including noninvasive breast cancer MCF-7) makes it an attractive lead compound for the development of specifically antimetastatic Ru complexes with low systemic toxicity. 相似文献
8.
This study investigated whether colloid-sized particles can enmesh and protect viruses from 254-nm ultraviolet (UV) light and sought to determine the particle characteristics (e.g. size, chemical composition) that are most relevant in causing a protective effect. Two viral surrogates (MS2 coliphage and bacteriophage T4), three types of particles (kaolin clay, humic acid powder, and activated sludge), two coagulants (alum and ferric chloride), two filtration conditions (none and 0.45 microm), and two UV doses (40 and 80 mJ/cm2 for MS2 coliphage; 2 and 7 mJ/cm2 for bacteriophage T4) were considered in a series of bench-scale UV collimated beam experiments. Transmission electron microscopy was used to qualitatively confirm the phage particle-association after coagulation. Humic acid and activated sludge floc particles shielded both viral surrogates to a statistically significant degree (with >99% confidence) relative to particle-free control conditions, while the kaolin clay particles provided no significant protection. The results of the study suggest that particles <2 microm in diameter are large enough to protect viruses from UV light and that particulate chemical composition (e.g. UV-absorbing organic content) may be a critical factor in the survival of particle-associated viruses during UV disinfection. 相似文献
9.
ABSTRACT Families are increasingly choosing to raise children in the growing number of private, high-rise apartment complexes developed in Australian capital cities. However, most of these developments have been designed for the childless and there are concerns as to how supportive these settings are for young children. This paper explores parents’ experiences of the environment surrounding their high-rise dwellings in an inner-city municipality of Melbourne, Australia using the participatory method, Photovoice. Ten parents photographed elements of their dwellings and environments that had positive or negative impacts on raising young children. Findings indicate that environments surrounding parents’ high-rise dwellings were used on a daily basis, often due to limited space within apartment complexes. However, aspects of this environment were challenging, requiring mutual accommodation between families and their immediate settings. This has implications for policy to ensure the neighbourhoods surrounding high-rise developments in inner-city areas are more child friendly. 相似文献
10.
A steady-state model for substrate removal in a rotating biological disc reactor is presented. The model considers the consumption of substrate by micro-organisms in the biofilm attached to the rotating disc, and mass transfer from the attached liquid film to the biofilm. A mass balance on substrate over the liquid in the trough provides an expression for effluent substrate in terms of the microbial kinetic constants, the geometry of the system and the operating conditions. In order to simplify the solution of the equations in the model, first order kinetics are assumed for the rate of microbial growth and substrate utilization. This simplified model can be solved, for example, by using a programmable calculator. The model predicts that the fractional removal of substrate per stage is strongly dependent on the hydraulic loading rate per unit disc area but independent of feed substrate concentration. It predicts constant removal independent of disc size provided the hydraulic loading per unit area is kept constant. The rotational speed has only a slight predicted effect on the rate of substrate removal. The predictions of the model are compared with published data from the literature for both domestic wastewater and some industrial wastes. Trends observed in the field are predicted qualitatively by the model. 相似文献