Despite efficient virological suppression on antiretroviral therapy (ART), people living with HIV (PLWH), experience an increased burden of premature co-morbidities, such as cancer and end-organ disease. With remaining challenges in terms of access to therapy, adherence and potential long-term drug toxicity, improving their long-term healthcare outcome, including new strategies for HIV clearance, remains a global priority. There is, therefore, an ongoing need to better characterize and harness the immune response in order to develop new strategies and supplement current therapeutic approaches for a "functional" cure. Current efforts toward HIV eradication to enhance immune recognition and elimination of persistently infected cells have highlighted the need for an optimized "kill" approach. Natural killer (NK) cells play an important role in antiviral defense and by virtue of their innate and adaptive features hold great promise as a focus of "kill" efforts. Galvanized by advances in the cancer field, NK cell exploitation, represents a transformative approach to augment HIV therapeutic modalities, circumventing many of the limitations inherent to T cell approaches. In this review we will discuss recent advances in our understanding of the development of NK cell adaptive/memory responses in HIV infection and highlight new and exciting opportunities to exploit the beneficial attributes of NK cells for HIV immunotherapy.Paracoccidioides brasiliensis is a temperature-dependent dimorphic fungus that causes systemic paracoccidioidomycosis, a granulomatous disease. The massive production of reactive oxygen species (ROS) by the host's cellular immune response is an essential strategy to restrain the fungal growth. Among the ROS, the hydroperoxides are very toxic antimicrobial compounds and fungal peroxidases are part of the pathogen neutralizing antioxidant arsenal against the host's defense. Among them, the peroxiredoxins are highlighted, since some estimates suggest that they are capable of decomposing most of the hydroperoxides generated in the host's mitochondria and cytosol. We presently characterized a unique P. brasiliensis 1-Cys peroxiredoxin (PbPrx1). Our results reveal that it can decompose hydrogen peroxide and organic hydroperoxides very efficiently. We showed that dithiolic, but not monothiolic compounds or heterologous thioredoxin reductant systems, were able to retain the enzyme activity. Structural analysis revealed that PbPrx1 has an α/β structure that is similar to the 1-Cys secondary structures described to date and that the quaternary conformation is represented by a dimer, independently of the redox state. We investigated the PbPrx1 localization using confocal microscopy, fluorescence-activated cell sorter, and immunoblot, and the results suggested that it localizes both in the cytoplasm and at the cell wall of the yeast and mycelial forms of P. brasiliensis, as well as in the yeast mitochondria. Our present results point to a possible role of this unique P. brasiliensis 1-Cys Prx1 in the fungal antioxidant defense mechanisms.Malassezia includes yeasts belong to the subphylum Ustilaginomycotina within the Basidiomycota. Malassezia yeasts are commonly found as commensals on human and animal skin. Nevertheless, Malassezia species are also associated with several skin disorders, such as dandruff/seborrheic dermatitis, atopic eczema, pityriasis versicolor, and folliculitis. More recently, associations of Malassezia with Crohn's disease, pancreatic ductal adenocarcinoma, and cystic fibrosis pulmonary exacerbation have been reported. The increasing availability of genomic and molecular tools have played a crucial role in understanding the genetic basis of Malassezia commensalism and pathogenicity. In the present review we report genomics advances in Malassezia highlighting unique features that potentially impacted Malassezia biology and host adaptation. Furthermore, we describe the recently developed protocols for Agrobacterium tumefaciens-mediated transformation in Malassezia, and their applications for random insertional mutagenesis or targeted gene replacement strategies.Sterile alpha motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) acts as a restriction factor for several RNA and DNA viruses by limiting the intracellular pool of deoxynucleoside triphosphates. Here, we investigated the regulation of SAMHD1 expression during human cytomegalovirus (HCMV) infection. SAMHD1 knockdown using shRNA increased the activity of the viral UL99 late gene promoter in human fibroblasts by 7- to 9-fold, confirming its anti-HCMV activity. We also found that the level of SAMHD1 was initially increased by HCMV infection but decreased partly at the protein level at late stages of infection. SAMHD1 loss was not observed with UV-inactivated virus and required viral DNA replication.  https://www.selleckchem.com/products/LY2603618-IC-83.html  This reduction of SAMHD1 was effectively blocked by MLN4924, an inhibitor of the Cullin-RING-E3 ligase (CRL) complexes, but not by bafilomycin A1, an inhibitor of vacuolar-type H+-ATPase. Indirect immunofluorescence assays further supported the CRL-mediated SAMHD1 loss at late stages of virus infection. Knockdown of CUL2 and to a lesser extent CUL1 using siRNA stabilized SAMHD1 in normal fibroblasts and inhibited SAMHD1 loss during virus infection. Altogether, our results demonstrate that SAMHD1 inhibits the growth of HCMV, but HCMV causes degradation of SAMHD1 at late stages of viral infection through the CRL complexes.Chronic hypertension during gestation is associated with an increased risk of adverse pregnancy outcomes including pre-eclampsia, fetal growth restriction and preterm birth. Research into new chemotherapeutic regimes for the treatment of hypertension in pregnancy is limited due to concerns about fetal toxicity and teratogenicity, and new therapeutic avenues are being sought in alternative physiological pathways. Historically, generation of the vasodilator nitric oxide was believed to be solely from L-arginine by means of nitric oxide synthase enzymes. Recently, a novel pathway for the reduction of dietary inorganic nitrate to nitrite by the bacteria in the oral cavity and subsequently to vasodilatory nitric oxide within the body has been uncovered. Dietary nitrate is abundant in green leafy vegetables, including beetroot and spinach, and reduction of exogenous nitrate to nitrite by oral bacteria can increase nitric oxide in the vasculature, lessening hypertension. Supplements rich in nitrate may be an attractive choice for treatment due to fewer side effects than drugs that are currently used to treat hypertensive pregnancy disorders.