Alkaloids: Therapeutic Potential against Human Coronaviruses

Alkaloids are a class of natural products known to have wide pharmacological activity and have great potential for the development of new drugs to treat a wide array of pathologies. Some alkaloids have antiviral activity and/or have been used as prototypes in the development of synthetic antiviral drugs. In this study, eleven anti-coronavirus alkaloids were identified from the scientific literature and their potential therapeutic value against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is discussed. In this study, in silico studies showed an affinity of the alkaloids for binding to the receptor-binding domain of the SARS-CoV-2 spike protein, putatively preventing it from binding to the host cell. Lastly, several mechanisms for the known anti-coronavirus activity of alkaloids were discussed, showing that the alkaloids are interesting compounds with potential use as bioactive agents against SARS-CoV-2

Belief in a zero-sum game and subjective well-being across 35 countries

This article presents a short research report on the relationship between perceived antagonism in social relations measured using the Belief in a Zero-Sum Game (BZSG) scale, life satisfaction, and positive and negative affect. Given that individuals who believe that life is like a zero-sum game are likely to perceive their daily interactions with others as unfair, we expected that individuals with high BZSG experience more negative affect and fewer positive one, resulting in a lower satisfaction with life. In addition, we examined whether country-level BZSG may play a moderating role in these associations. Data were collected from student samples (N=7146) in 35 countries. Multilevel modelling revealed that perceived social antagonism in social relations is negatively associated with satisfaction with life and that this relationship is mediated by both positive and negative affect at the individual level. The relation of individual BZSG and negative affect on satisfaction with life were weaker in societies with higher country-level BZSG, suggesting that the effects of BZSG may be less detrimental in these countries. These findings extend previous knowledge about predictors of life satisfaction and suggest that social beliefs might also be an important factor that influences subjective well-being. The contribution of the study is that the separate treatment of life satisfaction and positive and negative affect may be helpful in many research situations, particularly from a cross-cultural perspective

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Chemical conjugation of heterologous proteins on the surface of cowpea mosaic virus

10.1021/bc0402888Bioconjugate Chemistry154807-813BCCH

Supplementary Material for: Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety

The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations