Christopher nd Life Science Center
Christopher nd Life Science Center
Wang J.,Jilin University |
Zhang F.,Jilin University |
Wang Y.,Jilin University |
Fu Y.,Jilin University |
And 3 more authors.
3rd International Conference on Bioinformatics and Computational Biology 2011, BICoB 2011 | Year: 2011
Salt tolerance is an important agriculture character in Oryza sativa (rice). This paper proposed a framework of Support Vector Machine Recursive Feature Elimination (SVM-RFE) for analysing Oryza sativa microarray data from GEO. Through preliminary selection using t-test and iterative feature selection by SVM-RFE, we obtained 541 candidate genes. We analysed top 10 genes, which may play highly important roles in response to salt stress. The obtained results shed some light on the mechanism of salt tolerance in plants.
Michailidis E.,Christopher nd Life Science Center |
Singh K.,Christopher nd Life Science Center |
Ryan E.M.,Christopher nd Life Science Center |
Hachiya A.,Christopher nd Life Science Center |
And 9 more authors.
Cellular and Molecular Biology | Year: 2012
4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a highly potent inhibitor of HIV-1 reverse transcriptase (RT). We have previously shown that its exceptional antiviral activity stems from a unique mechanism of action that is based primarily on blocking translocation of RT; therefore we named EFdA a Translocation Defective RT Inhibitor (TDRTI). The N348I mutation at the connection subdomain (CS) of HIV-1 RT confers clinically significant resistance to both nucleoside (NRTIs) and non-nucleoside RT inhibitors (NNRTIs). In this study we tested EFdA-triphosphate (TP) together with a related compound, ENdA-TP (4'-ethynyl-2-amino-2'-deoxyadenosine triphosphate) against HIV-1 RTs that carry clinically relevant drug resistance mutations: N348I,D67N/K70R/L210Q/T215F, D67N/K70R/L210Q/T215F/N348I, and A62V/V75I/F77L/F116Y/Q151M. We demonstrate that these enzymes remain susceptible to TDRTIs. Similar to WT RT, the N348I RT is inhibited by EFdA mainly at the point of incorporation through decreased translocation. In addition, the N348I substitution decreases the RNase H cleavage of DNA terminated with EFdA-MP (T/PEFdA-MP). Moreover, N348I RT unblocks EFdA-terminated primers with similar efficiency as the WT enzyme, and further enhances EFdA unblocking in the background of AZT-resistance mutations. This study provides biochemical insights into the mechanism of inhibition of N348I RT by TDRTIs and highlights the excellent efficacy of this class of inhibitors against WT and drug-resistant HIV-1 RTs. © 2012.
Robbins K.L.,Christopher nd Life Science Center |
Glascock J.J.,Christopher nd Life Science Center |
Glascock J.J.,University of Missouri |
Osman E.Y.,Christopher nd Life Science Center |
And 4 more authors.
Human Molecular Genetics | Year: 2014
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss of a single gene, Survival Motor Neuron-1 (SMN1). Administration of a self-complementary Adeno-Associated Virus vector expressing full-length SMNcDNA (scAAV-SMN) has proven an effective means to rescue the SMA pheno type in SMA mice, either by intravenous (IV) or intracerebroventricular (ICV) administration at very early time points. We have recently shown that ICV delivery of scAAV9-SMN is more effective than a similardose of vector administered via an IV injection, there by providing an important mechanism to examine a timeline for rescuing the disease and determining the therapeutic window in a severe model of SMA. In this report, we utilized a relatively severe mouse model of SMA, SMND7. Animals were injected with scAAV9-SMN vector via ICV injection on a single day, from P2 through P8. At each deliverypoint from P2 through P8,scAAV9-SMN decreased disease severity. A near complete rescue was obtained following P2 injection while a P8 injection produced a ~40% extension in survival. Analysis of the underlying neuromuscular junction (NMJ) pathology revealed that late-stage delivery of the vector failed to provide protection from NMJ defects despite robust SMN expression in the central nervous system. While our study demonstrates that amaximal benefit is obtained when treatment is delivered during pre-symptomatic stages, significant therapeutic benefit can still be achieved after the onset of disease symptoms. © The Author 2014. Published by Oxford University Press. All rights reserved.
PubMed | Structural Biology Core and., University of Missouri, Kumamoto University, The Chemo Sero Therapeutic Research Institute Kaketsuken and 2 more.
Type: Journal Article | Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology | Year: 2015
Humanized monoclonal antibody KD-247 targets the Gly(312)-Pro(313)-Gly(314)-Arg(315) arch of the third hypervariable (V3) loop of the HIV-1 surface glycoprotein. It potently neutralizes many HIV-1 clade B isolates, but not of other clades. To understand the molecular basis of this specificity, we solved a high-resolution (1.55 ) crystal structure of the KD-247 antigen binding fragment and examined the potential interactions with various V3 loop targets. Unlike most antibodies, KD-247 appears to interact with its target primarily through light chain residues. Several of these interactions involve Arg(315) of the V3 loop. To evaluate the role of light chain residues in the recognition of the V3 loop, we generated 20 variants of KD-247 single-chain variable fragments with mutations in the antigen-binding site. Purified proteins were assessed for V3 loop binding using AlphaScreen technology and for HIV-1 neutralization. Our data revealed that recognition of the clade-specificity defining residue Arg(315) of the V3 loop is based on a network of interactions that involve Tyr(L32), Tyr(L92), and Asn(L27d) that directly interact with Arg(315), thus elucidating the molecular interactions of KD-247 with its V3 loop target.
Alfaro L.A.S.,University of British Columbia |
Dick S.A.,Ottawa Hospital Research Institute |
Dick S.A.,University of Ottawa |
Siegel A.L.,Christopher nd Life Science Center |
And 6 more authors.
Stem Cells | Year: 2011
Expression of the cell surface sialomucin CD34 is common to many adult stem cell types, including muscle satellite cells. However, no clear stem cell or regeneration-related phenotype has ever been reported in mice lacking CD34, and its function on these cells remains poorly understood. Here, we assess the functional role of CD34 on satellite cell-mediated muscle regeneration. We show that Cd34-/-mice, which have no obvious developmental phenotype, display a defect in muscle regeneration when challenged with either acute or chronic muscle injury. This regenerative defect is caused by impaired entry into proliferation and delayed myogenic progression. Consistent with the reported antiadhesive function of CD34, knockout satellite cells also show decreased motility along their host myofiber. Altogether, our results identify a role for CD34 in the poorly understood early steps of satellite cell activation and provide the first evidence that beyond being a stem cell marker, CD34 may play an important function in modulating stem cell activity. © AlphaMed Press.