The role of unintegrated DNA in HIV infection

Integration of the reverse transcribed viral genome into host chromatin is the hallmark of retroviral replication. Yet, during natural HIV infection, various unintegrated viral DNA forms exist in abundance. Though linear viral cDNA is the precursor to an integrated provirus, increasing evidence suggests that transcription and translation of unintegrated DNAs prior to integration may aid productive infection through the expression of early viral genes. Additionally, unintegrated DNA has the capacity to result in preintegration latency, or to be rescued and yield productive infection and so unintegrated DNA, in some circumstances, may be considered to be a viral reservoir. Recently, there has been interest in further defining the role and function of unintegrated viral DNAs, in part because the use of anti-HIV integrase inhibitors leads to an abundance of unintegrated DNA, but also because of the potential use of non-integrating lentiviral vectors in gene therapy and vaccines. There is now increased understanding that unintegrated viral DNA can either arise from, or be degraded through, interactions with host DNA repair enzymes that may represent a form of host antiviral defence. This review focuses on the role of unintegrated DNA in HIV infection and additionally considers the potential implications for antiviral therapy

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.Peer reviewe

Electrohydrodynamic phenomena

This work is a review article focused on exploring the interactions between external and induced electric fields and fluid motion, in the presence of embedded charges. Such interactions are generally termed electrohydrodynamics (EHD), which encompasses a vast range of flows stemming from multiscale physical effects. In this review article we shall mainly emphasize on two mechanisms of particular interest to fluid dynamists and engineers, namely electrokinetic flows and the leaky dielectric model. We shed light on the underlying physics behind the above mentioned phenomena and subsequently demonstrate the presence of a common underpinning pattern which governs any general electrohydrodynamic motion. Hence we go on to show that the seemingly unrelated fields of electrokinetics and the leaky dielectric models are indeed closely related to each other through the much celebrated Maxwell stresses, which have long been known as stresses caused in fluids in presence of electric and magnetic fields. Interactions between Maxwell Stresses and charges (for instance, in the form of ions) present in the fluid generates a body force on the same and eventually leads to flow actuation. We show that the manifestation of the Maxwell stresses itself depends on the charge densities, which in turn is dictated by the underlying motion of the fluid. We demonstrate how such inter-related dynamics may give rise intricately coupled and non-linear system of equations governing the dynamical state of the system. This article is mainly divided into two parts. First, we explore the realms of electrokinetics, wherein the formation and the structure of the so-called electrical double layer (EDL) is delineated. Subsequently, we review EDL’s relevance to electroosmosis and streaming potential with the key being the presence and absence of an applied pressure gradient. We thereafter focus on the leaky dielectric model, wherein the fundamental governing equations and its main difference with electrokinetics are described. We limit our attentions to the leaky dielectric motion around droplets and flat surfaces and subsequent interface deformation. To this end, through a rigorous review of a number of previous articles, we establish that the interface shapes can be finely tailored to achieve the desired geometrical characteristics by tuning the fluid properties. We further discuss previous studies, which have shown migration of droplets in the presence of strong electric fields. Finally, we describe the effects of external agents such as surface impurities on leaky dielectric motion and attempt to establish a qualitative connection between the leaky dielectric model and EDLs. We finish off with some pointers for further research activities and open questions in this field.by Aditya Bandopadhyay and Uddipta Ghos