Epigenetic Evolution of ACE2 and IL-6 Genes: Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 Susceptibility in Vertebrates

The current novel coronavirus disease (COVID-19) has spread globally within a matter of months. The virus establishes a success in balancing its deadliness and contagiousness, and causes substantial differences in susceptibility and disease progression in people of different ages, genders and pre-existing comorbidities. These host factors are subjected to epigenetic regulation; therefore, relevant analyses on some key genes underlying COVID-19 pathogenesis were performed to longitudinally decipher their epigenetic correlation to COVID-19 susceptibility. The genes of host angiotensin-converting enzyme 2 (ACE2, as the major virus receptor) and interleukin (IL)-6 (a key immuno-pathological factor triggering cytokine storm) were shown to evince active epigenetic evolution via histone modification and cis/trans-factors interaction across different vertebrate species. Extensive analyses revealed that ACE2 ad IL-6 genes are among a subset of non-canonical interferon-stimulated genes (non-ISGs), which have been designated for their unconventional responses to interferons (IFNs) and inflammatory stimuli through an epigenetic cascade. Furthermore, significantly higher positive histone modification markers and position weight matrix (PWM) scores of key cis-elements corresponding to inflammatory and IFN signaling, were discovered in both ACE2 and IL6 gene promoters across representative COVID-19-susceptible species compared to unsusceptible ones. The findings characterize ACE2 and IL-6 genes as non-ISGs that respond differently to inflammatory and IFN signaling from the canonical ISGs. The epigenetic properties ACE2 and IL-6 genes may serve as biomarkers to longitudinally predict COVID-19 susceptibility in vertebrates and partially explain COVID-19 inequality in people of different subgroups

Client Commitment Language During Motivational Interviewing Predicts Drug Use Outcomes

Client language from a motivational interview (MI) and drug use outcome were investigated. Interview videotapes of 84 drug abusers were coded for frequency and strength of utterances expressing commitment, desire, ability, need, readiness, and reasons to change or maintain their habit. Cluster analysis of proportion days abstinent (PDA) revealed 3 groups: high PDA at intake and follow-up (3, 6, 9, 12 months; maintainers); low intake PDA/high follow-up PDA (changers); and low intake PDA/low to moderate follow-up PDA (stragglers). Distinct group patterns emerged for commitment strength (CS) during MI. Clients dishonest in checklist self-report exhibited CS similar to stragglers. CS for client evaluation of a change plan predicted outcome PDA. CS was predicted by the strength of desire, ability, need, and reasons, but more strongly predicted outcome PDA, suggesting CS is a pathway for their influence on behavior

Integrate structural analysis, isoform diversity, and interferon-inductive propensity of ACE2 to predict SARS-CoV2 susceptibility in vertebrates

The current new coronavirus disease (COVID-19) has caused globally over 0.4/6 million confirmed deaths/infected cases across more than 200 countries. As the etiological coronavirus (a.k.a. SARS-CoV2) may putatively have a bat origin, our understanding about its intermediate reservoir between bats and humans, especially its tropism in wild and domestic animals are mostly unknown. This constitutes major concerns in public health for the current pandemics and potential zoonosis. Previous reports using structural analysis of the viral spike protein (S) binding its cell receptor of angiotensin-converting enzyme 2 (ACE2), indicate a broad potential of SARS-CoV2 susceptibility in wild and particularly domestic animals. Through integration of key immunogenetic factors, including the existence of S-binding-void ACE2 isoforms and the disparity of ACE2 expression upon early innate immune response, we further refine the SARS-CoV2 susceptibility prediction to fit recent experimental validation. In addition to showing a broad susceptibility potential across mammalian species based on structural analysis, our results also reveal that domestic animals including dogs, pigs, cattle and goats may evolve ACE2-related immunogenetic diversity to restrict SARS-CoV2 infections. Thus, we propose that domestic animals may be unlikely to play a role as amplifying hosts unless the virus has further species-specific adaptation. Findings may relieve relevant public concerns regarding COVID-19-like risk in domestic animals, highlight virus-host coevolution, and evoke disease intervention through targeting ACE2 molecular diversity and interferon optimization

Vegetation and Invertebrate Community Response to Eastern Hemlock Decline in Southern New England

The introduction of Adelges tsugae (Hemlock Woolly Adelgid [HWA]) to the eastern United States has had a devastating impact on Tsuga canadensis (Eastern Hemlock). Although much research has been done to assess HWA impacts on ecosystem processes and vegetation structure, few researchers have examined community-level changes in highly infested forest stands. Here we assess the impact of Eastern Hemlock mortality on vegetation and invertebrate diversity and community structure by comparing low-impact (healthy) stands and stands heavily impacted by HWA. We sampled the vegetative and invertebrate diversity of 8 sites (4 low impact and 4 high impact) in the summer and fall of 2008. We found a shift in the understory plant community and the canopy and subcanopy arthropod communities. Herbaceous plant species richness was significantly higher at high-impact sites, with Betula lenta (Black Birch) being the most common woody species. Overall, forest invertebrate community diversity (measured using the Shannon-Weaver diversity index) was greater in high- versus low-impact sites. Of the 21 indicator species significantly associated with a given forest type, 14 and 7 species were associated with high- and low-impact forests, respectively. Variation in arthropod community structure was driven by above-ground differences; ground-level arthropod community composition did not differ between high- and low-impact sites. These results demonstrate some of the biodiversity impacts that can result from the invasion of an exotic insect into forested systems

Adolescent Injury Rates

OBJECTIVE To describe the frequency of adolescent athlete injury based upon injury location, injury diagnosis, activity, playing surface, weather condition, and sport. MAIN.OUTCOME MEASUREMENTInjury frequency per injury location, diagnosis, activity, and playing surface were determined. Injury location and diagnosis frequency were reported by weather condition. Injuries per 1000 athletic exposures were analyzed by sport

The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia.

The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment. High treRNA also correlates with poor prognostic indicators such as unmutated IGHV and high ZAP70 protein expression. We validated these initial findings in samples collected in a clinical trial comparing the nucleoside analog fludarabine alone or in combination with the alkylating agent cyclophosphamide in untreated CLL samples collected prior to starting therapy (E2997). High expression of treRNA was independently prognostic for shorter progression free survival in patients receiving fludarabine plus cyclophosphamide. Given these results, in order to study the role of treRNA in DNA damage response we generated a model cell line system where treRNA was over-expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control line, there was less cell death in OSU-CLL over-expressing treRNA after exposure to fludarabine and mafosfamide, due in part to a reduction in DNA damage. Therefore, we suggest that treRNA is a novel biomarker in CLL associated with aggressive disease and poor response to chemotherapy through enhanced protection against cytotoxic mediated DNA damage

The Business Case for Racial Equity, 2013

Striving for racial equity -- a world where race is no longer a factor in the distribution of opportunity -- is a matter of social justice. But moving toward racial equity can generate significant economic returns as well. When people face barriers to achieving their full potential, the loss of talent, creativity, energy, and productivity is a burden not only for those disadvantaged, but for communities, businesses, governments, and the economy as a whole. Initial research on the magnitude of this burden in the United States (U.S.), as highlighted in this brief, reveals impacts in the trillions of dollars in lost earnings, avoidable public expenditures, and lost economic output