562 research outputs found

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

    Get PDF
    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

    Get PDF
    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

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

    Get PDF
    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

    Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation

    Get PDF
    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

    Convergent development of low-relatedness supercolonies in Myrmica ants.

    Get PDF
    Many ant species have independently evolved colony structures with multiple queens and very low relatedness among nestmate workers, but it has remained unclear whether low-relatedness kin structures can repeatedly arise in populations of the same species. Here we report a study of Danish island populations of the red ant Myrmica sulcinodis and show that it is likely that such repeated developments occur. Two microsatellite loci were used to estimate genetic differentiation (F(ST)) among three populations and nestmate relatedness within these populations. The F(ST) values were highly significant due to very different allele frequencies among the three populations with relatively few common alleles and relatively many rare alleles, possibly caused by single queen foundation and rare subsequent immigration. Given the isolation of the islands and the low investment in reproduction, we infer that each of the populations was most likely established by a single queen, even though all three extant populations now have within-colony relatedness 95%), and the genetic differentiation of nests showed a significantly positive correlation with the distance between them. Both male-biased sex-ratio and genetic viscosity are expected characteristics of populations where queens have very local dispersal and where new colonies are initiated through nest-budding. Based on a comparison with other M. sulcinodis populations we hypothesise a distinct succession of population types and suggest that this may be a possible pathway to unicoloniality, ie, development towards a complete lack of colony kin structure and unrelated nestmate workers

    Thiosquaramides: pH switchable anion transporters

    Get PDF
    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

    PPAR-α and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal

    Get PDF
    Many acute and chronic anaemias, including haemolysis, sepsis and genetic bone marrow failure diseases such as Diamond–Blackfan anaemia, are not treatable with erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU-Es) that respond to Epo are either too few in number or are not sensitive enough to Epo to maintain sufficient red blood cell production. Treatment of these anaemias requires a drug that acts at an earlier stage of red cell formation and enhances the formation of Epo-sensitive CFU-E progenitors. Recently, we showed that glucocorticoids specifically stimulate self-renewal of an early erythroid progenitor, burst-forming unit erythroid (BFU-E), and increase the production of terminally differentiated erythroid cells. Here we show that activation of the peroxisome proliferator-activated receptor α (PPAR-α) by the PPAR-α agonists GW7647 and fenofibrate synergizes with the glucocorticoid receptor (GR) to promote BFU-E self-renewal. Over time these agonists greatly increase production of mature red blood cells in cultures of both mouse fetal liver BFU-Es and mobilized human adult CD34+ peripheral blood progenitors, with a new and effective culture system being used for the human cells that generates normal enucleated reticulocytes. Although Ppara−/− mice show no haematological difference from wild-type mice in both normal and phenylhydrazine (PHZ)-induced stress erythropoiesis, PPAR-α agonists facilitate recovery of wild-type but not Ppara−/− mice from PHZ-induced acute haemolytic anaemia. We also show that PPAR-α alleviates anaemia in a mouse model of chronic anaemia. Finally, both in control and corticosteroid-treated BFU-E cells, PPAR-α co-occupies many chromatin sites with GR; when activated by PPAR-α agonists, additional PPAR-α is recruited to GR-adjacent sites and presumably facilitates GR-dependent BFU-E self-renewal. Our discovery of the role of PPAR-α agonists in stimulating self-renewal of early erythroid progenitor cells suggests that the clinically tested PPAR-α agonists we used may improve the efficacy of corticosteroids in treating Epo-resistant anaemias.United States. Defense Advanced Research Projects Agency (Grant HR0011-14-2-0005)United States. Army Medical Research and Materiel Command (Grant W81WH-12-1-0449)National Heart, Lung, and Blood Institute (Grant 2 P01 HL032262-25

    How common and frequent is heterosexual anal intercourse among South Africans? A systematic review and meta-analysis.

    Get PDF
    BACKGROUND: HIV is transmitted more effectively during anal intercourse (AI) than vaginal intercourse (VI). However, patterns of heterosexual AI practice and its contribution to South Africa's generalized epidemic remain unclear. We aimed to determine how common and frequent heterosexual AI is in South Africa. METHODS: We searched for studies reporting the proportion practising heterosexual AI (prevalence) and/or the number of AI and unprotected AI (UAI) acts (frequency) in South Africa from 1990 to 2015. Stratified random-effects meta-analysis by sub-groups was used to produce pooled estimates and assess the influence of participant and study characteristics on AI prevalence. We also estimated the fraction of all sex acts which were AI or UAI and compared condom use during VI and AI. RESULTS: Of 41 included studies, 31 reported on AI prevalence and 14 on frequency, over various recall periods. AI prevalence was high across different recall periods for sexually active general-risk populations (e.g. lifetime = 18.4% [95%CI:9.4-27.5%], three-month = 20.3% [6.1-34.7%]), but tended to be even higher in higher-risk populations such as STI patients and female sex workers (e.g. lifetime = 23.2% [0.0-47.4%], recall period not stated = 40.1% [36.2-44.0%]). Prevalence was higher in studies using more confidential interview methods. Among general and higher-risk populations, 1.2-40.0% and 0.7-21.0% of all unprotected sex acts were UAI, respectively. AI acts were as likely to be condom protected as vaginal acts. CONCLUSION: Reported heterosexual AI is common but variable among South Africans. Nationally and regionally representative sexual behaviour studies that use standardized recall periods and confidential interview methods, to aid comparison across studies and minimize reporting bias, are needed. Such data could be used to estimate the extent to which AI contributes to South Africa's HIV epidemic

    Adventurous Physical Activity Environments: A Mainstream Intervention for Mental Health

    Get PDF
    Adventurous physical activity has traditionally been considered the pastime of a small minority of people with deviant personalities or characteristics that compel them to voluntarily take great risks purely for the sake of thrills and excitement. An unintended consequence of these traditional narratives is the relative absence of adventure activities in mainstream health and well-being discourses and in large-scale governmental health initiatives. However, recent research has demonstrated that even the most extreme adventurous physical activities are linked to enhanced psychological health and well-being outcomes. These benefits go beyond traditional ‘character building’ concepts and emphasize more positive frameworks that rely on the development of effective environmental design. Based on emerging research, this paper demonstrates why adventurous physical activity should be considered a mainstream intervention for positive mental health. Furthermore, the authors argue that understanding how to design environments that effectively encourage appropriate adventure should be considered a serious addition to mainstream health and well-being discourse

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

    Get PDF
    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
    corecore