Communities of culturable yeasts and yeast-like fungi in oligotrophic hypersaline coastal waters of the Arabian Gulf surrounding Qatar

This report is the first investigation of yeast biodiversity from the oligotrophic hypersaline coastal waters of the Arabian Gulf surrounding Qatar. Yeasts and yeast-like fungi, were cultured from seawater sampled at 13 coastal areas surrounding Qatar over a period of 2 years (December 2013–September 2015). Eight hundred and forty-two isolates belonging to 82 species representing two phyla viz., Ascomycota (23 genera) and Basidiomycota (16 genera) were identified by molecular sequencing. The results indicated that the coastal waters of the Qatari oligotrophic marine environment harbor a diverse pool of yeast species, most of which have been reported from terrestrial, clinical and aquatic sources in various parts of the world. Five species, i.e., Candida albicans, C. parapsilosis, C. tropicalis, Pichia kudriavzevii and Meyerozyma guilliermondii (n?=?252/842; 30% isolates) are known as major opportunistic human pathogens. Fifteen species belonging to nine genera (n?=?498/842; 59%) and 12 species belonging to seven genera (n?=?459/842; 55%) are hydrocarbon degrading yeast and pollution indicator yeast species, respectively. Ascomycetous yeasts were predominant (66.38%; 559/842) as compared to their basidiomycetous counterparts (33.6%; 283/842). The most isolated yeast genera were Candida (28%; 236/842) (e.g., C. aaseri, C. boidinii, C. glabrata, C. intermedia, C. oleophila, C. orthopsilosis, C. palmioleophila, C. parapsilosis, C. pseudointermedia, C. rugopelliculosa, C. sake, C. tropicalis and C. zeylanoides), Rhodotorula (12.7%; 107/842), Naganishia (8.4%; 71/842), Aureobasidium (7.4%; 62/842), Pichia (7.3%; 62/842), and Debaryomyces (6.4%; 54/842). A total of eleven yeast species ( n = 38) isolated in this study are reported for the first time from the marine environment. Chemical testing demonstrated that seven out of the 13 sites had levels of total petroleum hydrocarbons (TPH) ranging from 200 to 900 µg/L, whereas 6 sites showed higher TPH levels (>?1000–21000 µg/L). The results suggest that the yeast community structure and density are impacted by various physico-chemical factors, namely total organic carbon, dissolved organic carbon and sulphur.

     

HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrest

Impaired adult neurogenesis has been observed in several neurodegenerative diseases, including human immunodeficiency virus (HIV-1)-associated dementia (HAD). Here we report that the HIV-envelope glycoprotein gp120, which is associated with HAD pathogenesis, inhibits proliferation of adult neural progenitor cells (aNPCs) in vitro and in vivo in the dentate gyrus of the hippocampus of HIV/gp120-transgenic mice. We demonstrate that HIV/gp120 arrests cell-cycle progression of aNPCs at the G1 phase via a cascade consisting of p38 mitogen-activated protein kinase (MAPK) --> MAPK-activated protein kinase 2 (a cell-cycle checkpoint kinase) --> Cdc25B/C. Our findings define a molecular mechanism that compromises adult neurogenesis in this neurodegenerative disorder.     

Ebola Cases and Health System Demand in Liberia

In 2014, a major epidemic of human Ebola virus disease emerged in West Africa, where human-to-human transmission has now been sustained for greater than 12 months. In the summer of 2014, there was great uncertainty about the answers to several key policy questions concerning the path to containment. What is the relative importance of nosocomial transmission compared with community-acquired infection? How much must hospital capacity increase to provide care for the anticipated patient burden? To which interventions will Ebola transmission be most responsive? What must be done to achieve containment? In recent years, epidemic models have been used to guide public health interventions. But, model-based policy relies on high quality causal understanding of transmission, including the availability of appropriate dynamic transmission models and reliable reporting about the sequence of case incidence for model fitting, which were lacking for this epidemic. To investigate the range of potential transmission scenarios, we developed a multi-type branching process model that incorporates key heterogeneities and time-varying parameters to reflect changing human behavior and deliberate interventions in Liberia. Ensembles of this model were evaluated at a set of parameters that were both epidemiologically plausible and capable of reproducing the observed trajectory. Results of this model suggested that epidemic outcome would depend on both hospital capacity and individual behavior. Simulations suggested that if hospital capacity was not increased, then transmission might outpace the rate of isolation and the ability to provide care for the ill, infectious, and dying. Similarly, the model suggested that containment would require individuals to adopt behaviors that increase the rates of case identification and isolation and secure burial of the deceased. As of mid-October, it was unclear that this epidemic would be contained even by 99% hospitalization at the planned hospital capacity. A new version of the model, updated to reflect information collected during October and November 2014, predicts a significantly more constrained set of possible futures. This model suggests that epidemic outcome still depends very heavily on individual behavior. Particularly, if future patient hospitalization rates return to background levels (estimated to be around 70%), then transmission is predicted to remain just below the critical point around R _eff = 1. At the higher hospitalization rate of 85%, this model predicts near complete elimination in March to June, 2015.     

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis

BackgroundObservational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.ConclusionsThis IPD meta-analysis found no evidence that COC or NET-EN use increases women’s risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.     

Concerted control of gliogenesis by InR/TOR and FGF signalling in the Drosophila post-embryonic brain

Glial cells are essential for the development and function of the nervous system. In the mammalian brain, vast numbers of glia of several different functional types are generated during late embryonic and early foetal development. However, the molecular cues that instruct gliogenesis and determine glial cell type are poorly understood. During post-embryonic development, the number of glia in the Drosophila larval brain increases dramatically, potentially providing a powerful model for understanding gliogenesis. Using glial-specific clonal analysis we find that perineural glia and cortex glia proliferate extensively through symmetric cell division in the post-embryonic brain. Using pan-glial inhibition and loss-of-function clonal analysis we find that Insulin-like receptor (InR)/Target of rapamycin (TOR) signalling is required for the proliferation of perineural glia. Fibroblast growth factor (FGF) signalling is also required for perineural glia proliferation and acts synergistically with the InR/TOR pathway. Cortex glia require InR in part, but not downstream components of the TOR pathway, for proliferation. Moreover, cortex glia absolutely require FGF signalling, such that inhibition of the FGF pathway almost completely blocks the generation of cortex glia. Neuronal expression of the FGF receptor ligand Pyramus is also required for the generation of cortex glia, suggesting a mechanism whereby neuronal FGF expression coordinates neurogenesis and cortex gliogenesis. In summary, we have identified two major pathways that control perineural and cortex gliogenesis in the post-embryonic brain and have shown that the molecular circuitry required is lineage specific.     

Regulated temporal-spatial astrocyte precursor cell proliferation involves BRAF signalling in mammalian spinal cord

Expansion of astrocyte populations in the central nervous system is characteristic of evolutionarily more complex organisms. However, regulation of mammalian astrocyte precursor proliferation during development remains poorly understood. Here, we used Aldh1L1-GFP to identify two morphologically distinct types of proliferative astrocyte precursors: radial glia (RG) in the ventricular zone and a second cell type we call an 'intermediate astrocyte precursor' (IAP) located in the mantle region of the spinal cord. Astrogenic RG and IAP cells proliferated in a progressive ventral-to-dorsal fashion in a tight window from embryonic day 13.5 until postnatal day 3, which correlated precisely with the pattern of active ERK signalling. Conditional loss of BRAF function using BLBP-cre resulted in a 20% decrease in astrocyte production, whereas expression of activated BRAFV600E resulted in astrocyte hyperproliferation. Interestingly, BRAFV600E mitogenic effects in astrocytes were restricted, in part, by the function of p16INK4A-p19(ARF), which limited the temporal epoch for proliferation. Together, these findings suggest that astrocyte precursor proliferation involves distinct RG and IAP cells; is subjected to temporal and spatial control; and depends in part on BRAF signalling at early stages of mammalian spinal cord development.     

Pathognomonic genetic expression profile within peripheral blood mononuclear cells of rheumatic heart disease patients

In this study we have tested the effects of d-propranolol (D-Pro) on the iron uptake, iron release and oxidative response of iron-loaded cells in a cellular model of iron-overload using isolated rat peritoneal macrophages incubated with iron-dextran (Fe-D). Pretreatment of macrophages with D-Pro (5–200 μ M) prior to Fe-D exposure decreased the cellular iron content and partially prevented iron release from latex-activated macrophages. Release of reactive oxygen species from activated cells was detected by dichlorodihydrofluorescein (DCDHF, 5 μ M) oxidation. We found that loading cells with Fe-D increased their response to latex, which was prevented by the lysosomotropic antioxidant agent D-Pro (10 μ M).     

Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants

In sickle cell anemia (SCA), inflammatory (i.e., intravascular sickling and transient vasoocclusive) events result in chronic endothelial activation. In addition to sickling behavior, sickle (SS) red blood cells exhibit abnormal interaction with the vascular endothelium, which is considered to have an important role in initiation of vasoocclusion. Upregulation of endothelial adhesion molecules caused by oxidants (and cytokines) may lead to increased SS red cell adhesion. We hypothesize that endothelial activation is indispensable in SS red cell adhesion to the endothelium and that antioxidants will have an inhibitory effect on this interaction. We examined the effect of selected antioxidants in ex vivo mesocecum vasculature, a well-established model that allows measurement of hemodynamic parameters and, by intravital microscopy, can allow quantification of adhesion. We tested antioxidant enzymes (SOD and catalase) and an intravascular SOD mimetic, polynitroxyl albumin (PNA), in the presence of platelet-activating factor (PAF); the latter causes endothelial oxidant generation and endothelial activation, which characterize SCA. In ex vivo preparations, PAF not only induced marked endothelial oxidant generation, it also enhanced SS red cell adhesion, resulting in frequent blockage of small-diameter venules. The adhesion, inversely related to venular diameter, and vasoocclusion were markedly inhibited by antioxidants, resulting in improved hemodynamics. PNA, the most effective antioxidant, also abolished SS red cell adhesion in non-PAF-activated preparations. Thus SS red cell adhesion and related vasoocclusion may be ameliorated by antioxidant therapy with a stable and long-acting molecule (e.g., PNA).