Smith

During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control HIV replication in extrafollicular regions, but not in the follicle. Here, we show CXCR5hiCD44hiCD8 T cells are a regulatory subset differing from conventional CD8 T cells, and constitute the majority of CD8 T cells in the follicle. This subset, CD8 follicular regulatory T cells (CD8 TFR), expand in chronic SIV infection, exhibit enhanced expression of Tim-3 and IL-10, and express less perforin compared to conventional CD8 T cells...

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No abstract text is available yet for this article.

Essential in the Green Revolution was the development of high-yielding dwarf varieties of rice (Oryza sativa L.), but their selection was not based on responses to water limitation. We studied physiological responses to progressive drought of the dwarf rice mutant, d1, in which the RGA1 gene, which encodes the GTP-binding α-subunit of the heterotrimeric G protein, is non-functional. Wild-type (WT) plants cease net carbon fixation 11 days after water is withheld, while d1 plants maintain net photosynthesis for an additional week...

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The brain is a major target for HIV infection and is a potential viral reservoir even in virologically well-controlled HIV-infected individuals. Data presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) suggested that during early HIV infection, CD4+ T cells in the meninges and choroid plexus serve as an important early site of HIV infection in the central nervous system (CNS), with brain macrophages and microglial cells becoming an important source of viral replication with advancing disease...

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A syndemic is defined as the convergence of two or more diseases that act synergistically to magnify the burden of disease. The intersection and syndemic interaction between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have had deadly consequences around the world. Without adequate control of the TB-HIV syndemic, the long-term TB elimination target set for 2050 will not be reached. There is an urgent need for additional resources and novel approaches for the diagnosis, treatment, and prevention of both HIV and TB...

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Genome editing driven by zinc-finger nucleases (ZFNs) yields high gene-modification efficiencies (>10%) by introducing a recombinogenic double-strand break into the targeted gene. The cleavage event is induced using two custom-designed ZFNs that heterodimerize upon binding DNA to form a catalytically active nuclease complex. Using the current ZFN architecture, however, cleavage-competent homodimers may also form that can limit safety or efficacy via off-target cleavage. Here we develop an improved ZFN architecture that eliminates this problem...

The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind...

The purpose of this study was to exam the impact of type 2 diabetes mellitus (T2DM) on CD4 cell count trends in adults with HIV. In a longitudinal retrospective study in an urban primary care HIV clinic in the southeastern United States from 2010 to 2012, patients with HIV medical charts were audited to obtain their CD4 cell count, diabetes status, weight, and demographic information. Rates of increase of CD4 T cell count (i.e. slopes) were obtained using a linear mixed-effects model. Most of the HIV-T2DM cohort (n = 262) and HIV-only cohort (n = 2399) were African American (76%) and male (77%)...

Custom-designed zinc finger nucleases (ZFNs), proteins designed to cut at specific DNA sequences, are becoming powerful tools in gene targeting--the process of replacing a gene within a genome by homologous recombination (HR). ZFNs that combine the non-specific cleavage domain (N) of FokI endonuclease with zinc finger proteins (ZFPs) offer a general way to deliver a site-specific double-strand break (DSB) to the genome. The development of ZFN-mediated gene targeting provides molecular biologists with the ability to site-specifically and permanently modify plant and mammalian genomes including the human genome via homology-directed repair of a targeted genomic DSB...

OBJECTIVES: Dolutegravir (DTG), a second-generation integrase strand transfer inhibitor (INSTI), is now among the most frequently used antiretroviral agents. However, recent reports have raised concerns about potential neurotoxicity. METHODS: We performed a retrospective analysis of a cohort of HIV-infected patients who had initiated an INSTI in two large German out-patient clinics between 2007 and 2016. We compared discontinuation rates because of adverse events (AEs) within 2 years of starting treatment with dolutegravir, raltegravir or elvitegravir/cobicistat...

There is a growing interest in essential oils (EOs) as possible alternatives for traditional chemical pesticides. This study was carried out to characterize the chemical composition of the three EOs extracted from Verbena officinalis, Majorana hortensis, and Salvia officinalis using gas chromatography (GC) and GC-mass spectrometry (GC-MS) and to evaluate in vitro their efficacy against some phyto or human pathogens. The antifungal activity was investigated against Colletotrichum acutatum and Botrytis cinerea in comparison with Azoxystrobin as a large spectrum fungicide...

After induced mutagenesis and transgenesis, genome editing is the next step in the development of breeding techniques. Genome editing using site-directed nucleases - including meganucleases, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR/Cas9 system - is based on the mechanism of double strand breaks. The nuclease is directed to cleave the DNA at a specific place of the genome which is then repaired by natural repair mechanisms. Changes are introduced during the repair that are either accidental or can be targeted if a DNA template with the desirable sequence is provided...

BACKGROUND: To investigate metabolic changes associated with second-line antiretroviral therapy (ART) following virological failure of first-line ART. METHODS: SECOND-LINE was an open-label randomized controlled trial. Participants were randomized 1:1 to receive ritonavir-boosted lopinavir (LPV/r) with 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N[t]RTI group) or raltegravir (RAL group). 210 participants had a dual energy X-ray absorptiometry (DXA)-scan at baseline, week 48 and 96...

Zinc-finger nucleases (ZFNs) are targetable DNA cleavage reagents that have been adopted as gene-targeting tools. ZFN-induced double-strand breaks are subject to cellular DNA repair processes that lead to both targeted mutagenesis and targeted gene replacement at remarkably high frequencies. This article briefly reviews the history of ZFN development and summarizes applications that have been made to genome editing in many different organisms and situations. Considerable progress has been made in methods for deriving zinc-finger sets for new genomic targets, but approaches to design and selection are still being perfected...

No abstract text is available yet for this article.

Previously, we reported that the rice dwarf mutant, d1, is defective in the alpha subunit of the heterotrimeric G protein (Galpha). In the present study, gibberellin (GA) signaling in d1 and the role of the Galpha protein in the GA-signaling pathway were investigated. Compared with the wild type, GA induction of alpha-amylase activity in aleurone cells of d1 was greatly reduced. Relative to the wild type, the GA(3)-treated aleurone layer of d1 had lower expression of Ramy1A, which encodes alpha-amylase, and OsGAMYB, which encodes a GA-inducible transcriptional factor, and no increase in expression of Ca(2 +)-ATPase...