Efficacy and Safety of Abacavir/Lamivudine/Zidovudine Plus Tenofovir in HBV/HIV-1 Coinfected Adults: 48-Week Data

In HBV/HIV-coinfected patients, the risk of end-stage liver disease and death is increased. This open-label, prospective, pilot study evaluated abacavir/lamivudine/zidovudine twice daily plus tenofovir once daily in HBV/HIV-coinfected antiretroviral-naïve subjects. Nine adults (8 males) enrolled, with baseline mean HIV-1 RNA = 4.5 log10 copies/mL, HBV DNA = 9.0 log10 copies/mL, and median CD4 count =158 cells/mm3. No subject had baseline ALT >5x ULN

Targeting DNA G-quadruplexes with helical small molecules.

We previously identified quinoline-based oligoamide helical foldamers and a trimeric macrocycle as selective ligands of DNA quadruplexes. Their helical structures might permit targeting of the backbone loops and grooves of G-quadruplexes instead of the G-tetrads. Given the vast array of morphologies G-quadruplex structures can adopt, this might be a way to achieve sequence selective binding. Here, we describe the design and synthesis of molecules based on macrocyclic and helically folded oligoamides. We tested their ability to interact with the human telomeric G-quadruplex and an array of promoter G-quadruplexes by using FRET melting assay and single-molecule FRET. Our results show that they constitute very potent ligands--comparable to the best so far reported. Their modes of interaction differ from those of traditional tetrad binders, thus opening avenues for the development of molecules specific for certain G-quadruplex conformations.We thank the “Cancer Research UK” for doctoral funding (SM) and “Association pour la recherche sur le cancer” for a postdoctoral fellowship (KLR). The Balasubramanian laboratory is core-funded by a programme grant from Cancer Research UK. TH acknowledges the NIH grant GM065367.This is the final version. It was first published by Wiley at http://onlinelibrary.wiley.com/doi/10.1002/cbic.201402439/abstract

B-1 Cell Heterogeneity and the Regulation of Natural and Antigen-Induced IgM Production.

A small subset of B cells, termed B-1 cells, with developmental origins, phenotypes, and functions that are distinct from those of conventional B cells exist in mice. It contributes the vast majority of spontaneously produced "natural" IgM. Natural IgM is constitutively produced, even in the absence of microbiota, and fulfills many distinct functions in tissue homeostasis and host defense. B-1 cells also respond with IgM production to innate signals and pathogen exposure, while maintaining steady-state levels natural IgM. Thus, within the B-1 cell pool, cells of distinct and heterogeneous functionality must exist to facilitate these different functions. This review considers three factors that may contribute to this heterogeneity: first, developmental differences regarding the origins of the precursors, second, tissue-specific signals that may differentially affect B-1 cells in the tissue compartments, and finally responsiveness to self-antigens as well as innate and antigen-specific signals. All three are likely to shape the repertoire and responsiveness of B-1 cells to homeostatic- and antigen-induced signals and thus contribute to the functional heterogeneity among these innate-like B cells

Mechanisms Linking Physical Activity with Psychiatric Symptoms Across the Lifespan:A Systematic Review

Background: Physical activity has been suggested as a protective factor against psychiatric symptoms. While numerous studies have focused on the magnitude of physical activity’s effect on psychiatric symptoms, few have examined the potential mechanisms. Objective: The current review aimed to synthesize scientific evidence of the mechanisms through which physical activity might reduce psychiatric symptoms across the lifespan. Methods: We included articles that were published before March 2022 from five electronic databases (MEDLINE, Web of Science, PsycINFO, Embase, and Cochrane). A qualitative synthesis of studies was conducted. The risk of bias assessment was performed using The Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews. Studies were included if they explored the possible mechanisms through which physical activity influences psychiatric symptoms (i.e., internalizing and externalizing symptoms) across the lifespan. Results: A total of 22 articles were included (three randomized controlled trials, four non-randomized controlled trials, three prospective longitudinal studies, and 12 cross-sectional studies). Overall, most of the studies focused on children, adolescents, and young adults. Our findings showed that self-esteem, self-concept, and self-efficacy were the only consistent paths through which physical activity influences psychiatric symptoms (specifically depressive and anxiety symptoms) across the lifespan. There were insufficient studies to determine the role of neurobiological mechanisms. Conclusions: Overall, future physical activity interventions with the purpose of improving mental health should consider these mechanisms (self-esteem, self-concept, self-efficacy) to develop more effective interventions. Clinical Trial Registration: The protocol of this study was registered in the PROSPERO database (registration number CRD42021239440) and published in April 2022.</p

Mechanisms linking physical activity with psychiatric symptoms across the lifespan:A protocol for a systematic review

INTRODUCTION: Persistent psychiatric symptomatology during childhood and adolescence predicts vulnerability to experience mental illness in adulthood. Physical activity is well-known to provide mental health benefits across the lifespan. However, the underlying mechanisms linking physical activity and psychiatric symptoms remain underexplored. In this context, we aim to systematically synthesise evidence focused on the mechanisms through which physical activity might reduce psychiatric symptoms across all ages. METHODS AND ANALYSIS: With the aid of a biomedical information specialist, we will develop a systematic search strategy based on the predetermined research question in the following electronic databases: MEDLINE, Embase, Web of Science, Cochrane and PsycINFO. Two independent reviewers will screen and select studies, extract data and assess the risk of bias. In case of inability to reach a consensus, a third person will be consulted. We will not apply any language restriction, and we will perform a qualitative synthesis of our findings as we anticipate that studies are scarce and heterogeneous. ETHICS AND DISSEMINATION: Only data that have already been published will be included. Then, ethical approval is not required. Findings will be published in a peer-reviewed journal and presented at conferences. Additionally, we will communicate our findings to healthcare providers and other sections of society (eg, through regular channels, including social media). PROSPERO REGISTRATION NUMBER: CRD42021239440

Characteristics of Ramachandran maps of L-alanine diamides as computed by various molecular mechanics, semiempirical and ab initio MO methods. A search for primary standard of peptide conformational stability

The optimized geometries and relative energies obtained by four force field and two semi-empirical methods were compared with ab initio results computed for formyl-L-alaninamide. Not all methods yielded the same number of minimum energy conformers. Furthermore, while the optimized geometries of the conformers found were comparable, the computed relative energies varied substantially. Also, the force field calculations produced Ramachandran maps that did not even have the appearance of the ab initio Ramachandran map. Correlating the ab initio relative energies (Delta E) or free energy (Delta G) with the log of relative populations, In(p(x)/p(gamma L)), led to linear relationships from which four conformers deviated; two of them (alpha(L) and epsilon(L)) were overly destabilized and two of them (gamma(L) and gamma(D)) were over-stabilized. It is suggested that, after such deviations are corrected, a primary standard may be obtained that might be useful in further investigations related to force-field parametrization as well as protein folding. (C) 1998 Elsevier Science B.V. All rights reserved