32 research outputs found
Navigating the Transition Between Military and College Life: Exploring College Veteran Help-Seeking Attitudes Toward Academic and Psychological Services
Student veteran enrollment in college is increasing at a significant rate and colleges are struggling to serve this population. Although research has indicated that college veteran academic performance is on par with nonveteran peers, college veterans are more likely to experience challenges related to mental and physical health. The purpose of this study was to understand better the help-seeking attitudes of veterans toward academic and psychological services so that colleges might enhance student veteran services. The research utilized a quantitative methodology to obtain help-seeking attitude data from college veteran participants. A survey was administered electronically to college veterans attending two State University of New York colleges. The results of the survey indicated that college veterans hold generally positive help-seeking attitudes toward academic and psychological services. Furthermore, the results indicated no significant difference between the help-seeking attitudes of veterans who experienced combat and veterans who had not experienced combat. The implications of these results are that college veterans find value in academic and psychological services and help-seeking attitudes may not impact veteran help-seeking behavior. Moreover, combat experience may not have an impact on help-seeking attitudes and further research on other possible contributing factors may be of value
Inhibition of Both HIV-1 Reverse Transcription and Gene Expression by a Cyclic Peptide that Binds the Tat-Transactivating Response Element (TAR) RNA
The RNA response element TAR plays a critical role in HIV replication by
providing a binding site for the recruitment of the viral transactivator protein
Tat. Using a structure-guided approach, we have developed a series of
conformationally-constrained cyclic peptides that act as structural mimics of
the Tat RNA binding region and block Tat-TAR interactions at nanomolar
concentrations in vitro. Here we show that these compounds
block Tat-dependent transcription in cell-free systems and in cell-based
reporter assays. The compounds are also cell permeable, have low toxicity, and
inhibit replication of diverse HIV-1 strains, including both CXCR4-tropic and
CCR5-tropic primary HIV-1 isolates of the divergent subtypes A, B, C, D and
CRF01_AE. In human peripheral blood mononuclear cells, the cyclic peptidomimetic
L50 exhibited an IC50 ∼250 nM. Surprisingly, inhibition of
LTR-driven HIV-1 transcription could not account for the full antiviral
activity. Timed drug-addition experiments revealed that L-50 has a bi-phasic
inhibition curve with the first phase occurring after HIV-1 entry into the host
cell and during the initiation of HIV-1 reverse transcription. The second phase
coincides with inhibition of HIV-1 transcription. Reconstituted reverse
transcription assays confirm that HIV-1 (−) strand strong stop DNA
synthesis is blocked by L50-TAR RNA interactions in-vitro.
These findings are consistent with genetic evidence that TAR plays critical
roles both during reverse transcription and during HIV gene expression. Our
results suggest that antiviral drugs targeting TAR RNA might be highly effective
due to a dual inhibitory mechanism
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
Navigating the Transition Between Military and College Life: Exploring College Veteran Help-Seeking Attitudes Toward Academic and Psychological Services
Student veteran enrollment in college is increasing at a significant rate and colleges are struggling to serve this population. Although research has indicated that college veteran academic performance is on par with nonveteran peers, college veterans are more likely to experience challenges related to mental and physical health. The purpose of this study was to understand better the help-seeking attitudes of veterans toward academic and psychological services so that colleges might enhance student veteran services. The research utilized a quantitative methodology to obtain help-seeking attitude data from college veteran participants. A survey was administered electronically to college veterans attending two State University of New York colleges. The results of the survey indicated that college veterans hold generally positive help-seeking attitudes toward academic and psychological services. Furthermore, the results indicated no significant difference between the help-seeking attitudes of veterans who experienced combat and veterans who had not experienced combat. The implications of these results are that college veterans find value in academic and psychological services and help-seeking attitudes may not impact veteran help-seeking behavior. Moreover, combat experience may not have an impact on help-seeking attitudes and further research on other possible contributing factors may be of value
Divergent Evolution in Reverse Transcriptase (RT) of HIV-1 Group O and M Lineages: Impact on Structure, Fitness, and Sensitivity to Nonnucleoside RT Inhibitors▿
Natural evolution in primate lentiviral reverse transcriptase (RT) appears to have been constrained by the necessity to maintain function within an asymmetric protein composed of two identical primary amino acid sequences (66 kDa), of which one is cleaved (51 kDa). In this study, a detailed phylogenetic analysis now segregates groups O and M into clusters based on a cysteine or tyrosine residue located at position 181 of RT and linked to other signature residues. Divergent evolution of two group O (C181 or Y181) and the main (Y181 only) HIV-1 lineages did not appreciably impact RT activity or function. Group O RT structural models, based on group M subtype B RT crystal structures, revealed that most evolutionarily linked amino acids appear on a surface-exposed region of one subunit while in a noncatalytic RT pocket of the other subunit. This pocket binds nonnucleoside RT inhibitors (NNRTI); therefore, NNRTI sensitivity was used to probe enzyme differences in these group O and M lineages. In contrast to observations showing acquired drug resistance associated with fitness loss, the C181Y mutation in the C181 group O lineage resulted in a loss of intrinsic NNRTI resistance and was accompanied by fitness loss. Other mutations linked to the NNRTI-resistant C181 lineage also resulted in altered NNRTI sensitivity and a net fitness cost. Based on RT asymmetry and conservation of the intricate reverse transcription process, millions of years of divergent primate lentivirus evolution may be constrained to discrete mutations that appear primarily in the nonfunctional, solvent-accessible NNRTI binding pocket