Excess maternal salt or fructose intake programmes sex-specific, stress- and fructose-sensitive hypertension in the offspring

The Western diet is typically high in salt and fructose, which have pressor activity. Maternal diet can affect offspring blood pressure, but the extent to which maternal intake of excess salt and fructose may influence cardiovascular function of the offspring is unknown. We sought to determine the effect of moderate maternal dietary intake of salt and/or fructose on resting and stimulated cardiovascular function of the adult male and female offspring. Pregnant rats were fed purified diets (±4 % salt) and water (±10 % fructose) before and during gestation and through lactation. Male and female offspring were weaned onto standard laboratory chow. From 9 to 14 weeks of age, cardiovascular parameters (basal, circadian and stimulated) were assessed continuously by radiotelemetry. Maternal salt intake rendered opposite-sex siblings with a 25-mmHg difference in blood pressure as adults; male offspring were hypertensive (15 mmHg mean arterial pressure (MAP)) and female offspring were hypotensive (10 mmHg MAP) above and below controls, respectively. Sex differences were unrelated to endothelial nitric oxide activity in vivo, but isolation-induced anxiety revealed a significantly steeper coupling between blood pressure and heart rate in salt-exposed male offspring but not in female offspring. MAP of all offspring was refractory to salt loading but sensitive to subsequent dietary fructose, an effect exacerbated in female offspring from fructose-fed dams. Circadian analyses of pressure in all offspring revealed higher mean set-point for heart rate and relative non-dipping of nocturnal pressure. In conclusion, increased salt and fructose in the maternal diet has lasting effects on offspring cardiovascular function that is sex-dependent and related to the offspring’s stress–response axis

Waste-derived inosilicate carrier for antimicrobial Zn2+ and Ag+ ions

Recent research by the authors has demonstrated that the inosilicate, lithium metasilicate (Li2SiO3), can be prepared by hydrothermal synthesis from waste green container glass (GCG) [1,2]. This study investigated the potential of this material to be ion-exchanged with antimicrobial Zn2+ or Ag+ ions for use as a filler in polymer composites. Antimicrobial polymer composites are an advantage in applications where the communication of pathogenic bacteria poses a problem, such as hospitals, abattoirs and food-processing factories. The naturally-occurring biodegradable mucopolysaccharide derivative, chitosan, was used as a model polymer in this study. The lithium metasilicate product was synthesised from GCG in LiOH(aq) and ion-exchanged with either Zn2+ or Ag+ ions via batch sorption. The in vitro antibacterial properties of solvent-cast metasilicate-chitosan composite membranes were then evaluated by zone of inhibition against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus

HIV testing and engagement with the HIV treatment cascade among men who have sex with men in Africa: A systematic review and meta-analysis

Background HIV disproportionately affects gay, bisexual, and other men who have sex with men (MSM) in Africa, where many countries criminalise same-sex behaviour. We assessed changes in the engagement of African MSM with HIV testing and treatment cascade stages over time, and the influence of anti-LGBT legislation and stigma. Methods We systematically searched the peer-reviewed literature to October 10th , 2018 for studies and extracted or derived estimates of HIV testing and/or engagement with the HIV treatment cascade among African MSM from published reports. We derived pooled estimates using inverse-variance random-effects models. We used subgroup and meta-regression analysis to assess associations between testing and status awareness outcomes and study and participant characteristics including the severity of country-level anti-LGBT legislation. Findings Our searches identified 75 independent eligible studies that provided estimates for 44,993 MSM across one or more of five testing and treatment cascade outcomes. HIV testing increased significantly over time overall, with pooled overall proportions of MSM ever tested of 67·3% (95%Confidence interval 62·1-72·3%,N=44) and tested in the past 12 months of 50·1% (42·4-57·8%,N=31) post-2011 – 14% and 18% points higher than pre-2011, respectively. Post-2011, ever testing was highest in Southern(80·0%) and lowest in Northern(34·4%) and Central(56·1%) Africa, with the greatest increase in Western Africa(from 42·4 to 70·9%). Levels of both testing outcomes and status awareness were statistically significantly lower in countries with the most severe anti-LGBT legislation. Few estimates were available for later stages of the treatment cascade. Available data post61 2011 suggest that the pooled proportion of MSM HIV-positive aware has remained low (18·5%, 12·5-25·3%,N=28) whereas proportions of current ART use were 23·7% (15·5- 33·0%,N=14) among all MSM living with HIV and 53·4% (36·9-69·5%,N=6) among MSM HIV-positive aware. Levels of viral suppression among MSM currently on ART were good (pooled: 75·6%, 64·4-85·5%,N=4), but low among all MSM living with HIV (pooled: 24·7%, 18·8-31·2%,N=4). Interpretation Available data suggests that levels of HIV status awareness among MSM living with HIV in Africa remain low, despite recent improvements in HIV testing; limited data is available on levels of engagement in care, ART use and viral suppression. We found that severe anti LGBT legislation was associated with lower HIV testing and status awareness. Achieving UNAIDS 90-90-90 targets will require substantial improvements

Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation

An effect of thyroid hormone (TH) on erythropoiesis has been known for more than a century but the molecular mechanism(s) by which TH affects red cell formation is still elusive. Here we demonstrate an essential role of TH during terminal human erythroid cell differentiation; specific depletion of TH from the culture medium completely blocked terminal erythroid differentiation and enucleation. Treatment with TRβ agonists stimulated premature erythroblast differentiation in vivo and alleviated anemic symptoms in a chronic anemia mouse model by regulating erythroid gene expression. To identify factors that cooperate with TRβ during human erythroid terminal differentiation, we conducted RNA-seq in human reticulocytes and identified nuclear receptor coactivator 4 (NCOA4) as a critical regulator of terminal differentiation. Furthermore, Ncoa4 −/− mice are anemic in perinatal periods and fail to respond to TH by enhanced erythropoiesis. Genome-wide analysis suggests that TH promotes NCOA4 recruitment to chromatin regions that are in proximity to Pol II and are highly associated with transcripts abundant during terminal differentiation. Collectively, our results reveal the molecular mechanism by which TH functions during red blood cell formation, results that are potentially useful to treat certain anemias. Keywords: thyroid hormone; erythropoiesis; NCOA4; nuclear receptorUnited States. Defense Advanced Research Projects Agency (Award HR0011-14-2-0005)United States. Department of Defense (Award W81WH-12-1-0449)National Heart, Lung, and Blood Institute (Grant P01 HL032262-25

Conservation of co-evolved interactions: understanding the Maculinea–Myrmica complex

1. The six papers in this Special Issue of Insect Conservation and Diversity are presented as a gedenkschrift honouring ground‐breaking contributions made by the late Graham Elmes towards understanding the biology of Myrmica ants and their social parasites. 2. A common theme is that each research paper contributes new knowledge applicable to the future survival of Maculinea (= Phengaris) species of butterflies, which have become flagships for insect conservation across Europe. All Maculinea species are highly specialised, with larvae that feed briefly on a specific foodplant before living underground for 11–23 months as social parasites of Myrmica colonies. 3. This introductory overview provides a brief history of the research that has led to the current collection, with emphasis on Graham Elmes' life and work. It is followed by three research papers that illustrate the diversity, socio‐biology and ecology of Myrmica ants. A fourth describes an extreme adaptation that increases the efficiency with which some populations of Maculinea larvae exploit the resources within Myrmica nests. A fifth, more theoretical, paper models the constraints that typically lead to host specificity among social parasites and explores why host switches are rare and quick

Effect of oleic acid supplementation on prostaglandin production in maternal endometrial and fetal allantochorion cells isolated from late gestation ewes

Elevated circulating non-esterified fatty acids including oleic acid (OA) are associated with many pregnancy related complications. Prostaglandins (PGs) play crucial roles during parturition. We investigated the effect of OA supplementation on PG production using an in vitro model of ovine placenta

The association between heterosexual anal intercourse and HIV acquisition in three prospective cohorts of women

The extent to which receptive anal intercourse (RAI) increases the HIV acquisition risk of women compared to receptive vaginal intercourse (RVI) is poorly understood. We evaluated RAI practice over time and its association with HIV incidence during three prospective HIV cohorts of women: RV217, MTN-003 (VOICE), and HVTN 907. At baseline, 16% (RV 217), 18% (VOICE) of women reported RAI in the past 3 months and 27% (HVTN 907) in the past 6 months, with RAI declining during follow-up by around 3-fold. HIV incidence in the three cohorts was positively associated with reporting RAI at baseline, albeit not always significantly. The adjusted hazard rate ratios for potential confounders (aHR) were 1.1 (95% Confidence interval: 0.8-1.5) for VOICE and 3.3 (1.6-6.8) for RV 217, whereas the ratio of cumulative HIV incidence by RAI practice was 1.9 (0.6-6.0) for HVTN 907. For VOICE, the estimated magnitude of association increased slightly when using a time-varying RAI exposure definition (aHR = 1.2; 0.9-1.6), and for women reporting RAI at every follow-up survey (aHR = 2.0 (1.3-3.1)), though not for women reporting higher RAI frequency (> 30% acts being RAI vs. no RAI in the past 3 months; aHR = 0.7 (0.4-1.1)). Findings indicated precise estimation of the RAI/HIV association, following multiple RVI/RAI exposures, is sensitive to RAI exposure definition, which remain imperfectly measured. Information on RAI practices, RAI/RVI frequency, and condom use should be more systematically and precisely recorded and reported in studies looking at sexual behaviors and HIV seroconversions; standardized measures would aid comparability across geographies and over time

The Effect of Systemic Racism and Homophobia on Police Enforcement and Sexual and Emotional Violence among Sex Workers in East London:Findings from a Cohort Study

There is extensive qualitative evidence of violence and enforcement impacting sex workers who are ethnically or racially minoritized, and gender or sexual minority sex workers, but there is little quantitative evidence. Baseline and follow-up data were collected among 288 sex workers of diverse genders (cis/transgender women and men and non-binary people) in London (2018–2019). Interviewer-administered and self-completed questionnaires included reports of rape, emotional violence, and (un)lawful police encounters. We used generalized estimating equation models (Stata vs 16.1) to measure associations between (i) ethnic/racial identity (Black, Asian, mixed or multiple vs White) and recent (6 months) or past police enforcement and (ii) ethnic/racial and sexual identity (lesbian, gay or bisexual (LGB) vs. heterosexual) with recent rape and emotional violence (there was insufficient data to examine  the association with transgender/non-binary identities). Ethnically/racially minoritized sex workers (26.4%) reported more police encounters partly due to increased representation in street settings (51.4% vs 30.7% off-street, p = 0.002). After accounting for street setting, ethnically/racially minoritized sex workers had higher odds of recent arrest (adjusted odds ratio 2.8, 95% CI 1.3–5.8), past imprisonment (aOR 2.3, 95% CI 1.1–5.0), police extortion (aOR 3.3, 95% CI 1.4–7.8), and rape (aOR 3.6, 95% CI 1.1–11.5). LGB-identifying sex workers (55.4%) were more vulnerable to rape (aOR 2.4, 95% CI 1.1–5.2) and emotional violence. Sex workers identifying as ethnically/racially minoritized (aOR 2.1, 95% CI 1.0–4.5), LGB (aOR 2.0, 95% CI 1.0–4.0), or who use drugs (aOR 2.0, 95% CI 1.1–3.8) were more likely to have experienced emotional violence than white-identifying, heterosexual or those who did not use drugs. Experience of any recent police enforcement was associated with increased odds of rape (aOR 3.6, 95% CI 1.3–8.4) and emotional violence (aOR 4.9, 95% CI 1.8–13.0). Findings show how police enforcement disproportionately targets ethnically/racially minoritized sex workers and contributes to increased risk of rape and emotional violence, which is elevated among sexual and ethnically/racially minoritized workers

Thiosquaramides: pH switchable anion transporters

The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquar-amides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with pKa values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH