Iodine status of soils, grain crops, and irrigation waters in Pakistan

A study was carried out across 86 locations of the country to investigate iodine supply potential of soils, grains and underground waters for onward design of an environmental intervention in Pakistan. Wheat crops were the principal crop in this study since it supplies 75 % of calorific energy in an average Pakistani diet. TMAH-extractable iodine in soils provided a geometric mean of 0.66 µg g−1, far lower than the worldwide mean of 3.0 µg g−1 for soil iodine. Bioavailable (water-extractable) iodine concentration had a geometric mean of 2.4 % (of TMAH-extractable iodine). Median iodine concentrations in tube well sourced waters were 7.3 µg L−1. Median wheat grain-iodine concentrations were 0.01 µg g−1. In most of the grain samples, TMAH-extractable iodine was below detection limit of 0.01 µg g−1. The highest wheat grain iodine was measured on a soil having highest TMAH-extractable iodine. An iodine intake of 25.4 µg a day has been estimated based on median wheat grain iodine measured and groundwater consumption compared to world health organisation (WHO) recommendations of iodine intake of 150 µg a day. This nominal intake of iodine is alarming since 60 % of Pakistani households do not consume iodised salt

Contribution of siderophore systems to growth and urinary tract colonization of asymptomatic bacteriuria Escherichia coli

The molecular mechanisms that define asymptomatic bacteriuria (ABU) E. coli colonization of the human urinary tract remain to be properly elucidated. Here we utilize ABU E. coli strain 83972 as a model to dissect the contribution of siderophores to iron acquisition, growth, fitness and colonization of the urinary tract. We show that E. coli 83972 produces enterobactin, salmochelin, aerobactin and yersiniabactin, and examine the role of these systems using mutants defective in siderophore biosynthesis and uptake. Enterobactin and aerobactin contributed most to total siderophore activity and growth in defined iron-deficient media. No siderophores were detected in an 83972 quadruple mutant deficient in all four siderophore biosynthesis pathways; this mutant did not grow in defined iron-deficient media but grew in iron-limited pooled human urine due to iron uptake via the FecA ferric citrate receptor. In a mixed 1:1 growth assay with 83972 there was no fitness disadvantage of the 83972 quadruple biosynthetic mutant, demonstrating its capacity to act as a ‘cheater’ and utilize siderophores produced by the wild-type strain for iron uptake. An 83972 enterobactin/salmochelin double receptor mutant was outcompeted by 83972 in human urine and the mouse urinary tract, indicating a role for catecholate receptors in urinary tract colonization

Disruption of Intraflagellar Transport in Adult Mice Leads to Obesity and Slow-Onset Cystic Kidney Disease

SummaryThe assembly of primary cilia is dependant on intraflagellar transport (IFT), which mediates the bidirectional movement of proteins between the base and tip of the cilium. In mice, congenic mutations disrupting genes required for IFT (e.g., Tg737 or the IFT kinesin Kif3a) are embryonic lethal, whereas kidney-specific disruption of IFT results in severe, rapidly progressing cystic pathology [1–3]. Although the function of primary cilia in most tissues is unknown, in the kidney they are mechanosenstive organelles that detect fluid flow through the tubule lumen [4]. The loss of this flow-induced signaling pathway is thought to be a major contributing factor to cyst formation [5–7]. Recent data also suggest that there is a connection between ciliary dysfunction and obesity as evidenced by the discovery that proteins associated with human obesity syndromes such as Alström and Bardet-Biedl localize to this organelle [8]. To more directly assess the importance of cilia in postnatal life, we utilized conditional alleles of two ciliogenic genes (Tg737 and Kif3a) to systemically induce cilia loss in adults. Surprisingly, the cystic kidney pathology in these mutants is dependent on the time at which cilia loss was induced, suggesting that cyst formation is not simply caused by impaired mechanosensation. In addition to the cystic pathology, the conditional cilia mutant mice become obese, are hyperphagic, and have elevated levels of serum insulin, glucose, and leptin. We further defined where in the body cilia are required for normal energy homeostasis by disrupting cilia on neurons throughout the central nervous system and on pro-opiomelanocortin-expressing cells in the hypothalamus, both of which resulted in obesity. These data establish that neuronal cilia function in a pathway regulating satiety responses

Modulation of Allergic Inflammation in the Nasal Mucosa of Allergic Rhinitis Sufferers With Topical Pharmaceutical Agents

Allergic rhinitis (AR) is a chronic upper respiratory disease estimated to affect between 10 and 40% of the worldwide population. The mechanisms underlying AR are highly complex and involve multiple immune cells, mediators, and cytokines. As such, the development of a single drug to treat allergic inflammation and/or symptoms is confounded by the complexity of the disease pathophysiology. Complete avoidance of allergens that trigger AR symptoms is not possible and without a cure, the available therapeutic options are typically focused on achieving symptomatic relief. Topical therapies offer many advantages over oral therapies, such as delivering greater concentrations of drugs to the receptor sites at the source of the allergic inflammation and the reduced risk of systemic side effects. This review describes the complex pathophysiology of AR and identifies the mechanism(s) of action of topical treatments including antihistamines, steroids, anticholinergics, decongestants and chromones in relation to AR pathophysiology. Following the literature review a discussion on the future therapeutic strategies for AR treatment is provided

'It's because I like things… it's a status and he buys me airtime': exploring the role of transactional sex in young women's consumption patterns in rural South Africa (secondary findings from HPTN 068).

BACKGROUND: 'Transactional sex', defined as a non-marital, non-commercial sexual relationship in which money or material goods are exchanged for sex, is associated with young women's increased vulnerability to HIV infection. Existing research illustrates that the motivations for transactional sex are complex. The fulfilment of psycho-social needs such as the need to belong to a peer group are important factors underlying young women's desires to obtain certain consumption items and thus engage in transactional sex. METHODS: We use a mixed-methods approach to explore the relationship between transactional sex and consumption patterns among young women in rural Mpumalanga province, South Africa. In the secondary analysis of 693 sexually active young women, we use factor analysis to group the different consumption items and we use multivariable logistic regression to demonstrate the relationship between transactional sex and consumption patterns. The qualitative study uses five focus group discussions and 19 in-depth interviews to explore further young women's motivations for acquiring different consumption items. RESULTS: The quantitative results show that young women that engage in transactional sex have higher odds of consuming items for entertainment (e.g., movie tickets) than on practical items (e.g., food and groceries). The qualitative findings also revealed that young women's perceptions of items that were considered a 'need' were strongly influenced by peer pressure and a desire for improved status. Further, there was a perception that emerged from the qualitative data that relationships with sugar daddies offered a way to acquire consumer goods associated with a 'modern lifestyle', such as items for personal enhancement and entertainment. However, young women seem aware of the risks associated with such relationships. More importantly, they also develop relationship with partners of similar age, albeit with the continued expectation of material exchange, despite engaging in the relationship for love. CONCLUSION: This study shows that young women are willing to take certain risks in order to have a degree of financial independence. Interventions that provide alternative methods of attaining this independence, such as the provision of cash transfers may have potential in preventing them from engaging in transactional relationships. Further, the psycho-social reasons that drive young women's motivations for consumption items resulting in risky sexual behaviours need to be better understood

The β-isoform of BCCIP promotes ADP release from the RAD51 presynaptic filament and enhances homologous DNA pairing

Homologous recombination (HR) is a template-driven repair pathway that mends DNA double-stranded breaks (DSBs), and thus helps to maintain genome stability. The RAD51 recombinase facilitates DNA joint formation during HR, but to accomplish this task, RAD51 must be loaded onto the single-stranded DNA. DSS1, a candidate gene for split hand/split foot syndrome, provides the ability to recognize RPA-coated ssDNA to the tumor suppressor BRCA2, which is complexed with RAD51. Together BRCA2-DSS1 displace RPA and load RAD51 onto the ssDNA. In addition, the BRCA2 interacting protein BCCIP normally colocalizes with chromatin bound BRCA2, and upon DSB induction, RAD51 colocalizes with BRCA2-BCCIP foci. Down-regulation of BCCIP reduces DSB repair and disrupts BRCA2 and RAD51 foci formation. While BCCIP is known to interact with BRCA2, the relationship between BCCIP and RAD51 is not known. In this study, we investigated the biochemical role of the β-isoform of BCCIP in relation to the RAD51 recombinase. We demonstrate that BCCIPβ binds DNA and physically and functionally interacts with RAD51 to stimulate its homologous DNA pairing activity. Notably, this stimulatory effect is not the result of RAD51 nucleoprotein filament stabilization; rather, we demonstrate that BCCIPβ induces a conformational change within the RAD51 filament that promotes release of ADP to help maintain an active presynaptic filament. Our findings reveal a functional role for BCCIPβ as a RAD51 accessory factor in HR

Imagining the future at the global and national scale: a comparative study of British and Dutch press coverage of Rio 1992 and Rio 2012

Climate change and imagined futures are intricately linked, discussed by policymakers and reported in the media. In this article we focus on the construction of future expectation in the press coverage of the 1992 and 2012 United Nations conferences in Rio de Janeiro in British and Dutch national newspapers. We use a novel combination of methods, semantic co-word networks and metaphor analysis to analyse imagined futures. Our findings show that between 1992 and 2012 there was a switch from future-oriented hope to past-oriented disappointment regarding implementing international agreements on climate change policy. While the UK focused on global issues, the Netherlands focused on national (including colonial) and local ones, reflecting different views and expectations about the future of climate change adaptation and mitigation

'It’s because I like things… it’s a status and he buys me airtime': exploring the role of transactional sex in young women’s consumption patterns in rural South Africa (secondary findings from HPTN 068)

Abstract: Background ‘Transactional sex’, defined as a non-marital, non-commercial sexual relationship in which money or material goods are exchanged for sex, is associated with young women’s increased vulnerability to HIV infection. Existing research illustrates that the motivations for transactional sex are complex. The fulfilment of psycho-social needs such as the need to belong to a peer group are important factors underlying young women’s desires to obtain certain consumption items and thus engage in transactional sex. Methods We use a mixed-methods approach to explore the relationship between transactional sex and consumption patterns among young women in rural Mpumalanga province, South Africa. In the secondary analysis of 693 sexually active young women, we use factor analysis to group the different consumption items and we use multivariable logistic regression to demonstrate the relationship between transactional sex and consumption patterns. The qualitative study uses five focus group discussions and 19 in-depth interviews to explore further young women’s motivations for acquiring different consumption items. Results The quantitative results show that young women that engage in transactional sex have higher odds of consuming items for entertainment (e.g., movie tickets) than on practical items (e.g., food and groceries). The qualitative findings also revealed that young women’s perceptions of items that were considered a ‘need’ were strongly influenced by peer pressure and a desire for improved status. Further, there was a perception that emerged from the qualitative data that relationships with sugar daddies offered a way to acquire consumer goods associated with a ‘modern lifestyle’, such as items for personal enhancement and entertainment. However, young women seem aware of the risks associated with such relationships. More importantly, they also develop relationship with partners of similar age, albeit with the continued expectation of material exchange, despite engaging in the relationship for love. Conclusion This study shows that young women are willing to take certain risks in order to have a degree of financial independence. Interventions that provide alternative methods of attaining this independence, such as the provision of cash transfers may have potential in preventing them from engaging in transactional relationships. Further, the psycho-social reasons that drive young women’s motivations for consumption items resulting in risky sexual behaviours need to be better understood

Regulation of Hepatic Triacylglycerol Metabolism by CGI-58 Does Not Require ATGL Co-activation

SummaryAdipose triglyceride lipase (ATGL) and comparative gene identification 58 (CGI-58) are critical regulators of triacylglycerol (TAG) turnover. CGI-58 is thought to regulate TAG mobilization by stimulating the enzymatic activity of ATGL. However, it is not known whether this coactivation function of CGI-58 occurs in vivo. Moreover, the phenotype of human CGI-58 mutations suggests ATGL-independent functions. Through direct comparison of mice with single or double deficiency of CGI-58 and ATGL, we show here that CGI-58 knockdown causes hepatic steatosis in both the presence and absence of ATGL. CGI-58 also regulates hepatic diacylglycerol (DAG) and inflammation in an ATGL-independent manner. Interestingly, ATGL deficiency, but not CGI-58 deficiency, results in suppression of the hepatic and adipose de novo lipogenic program. Collectively, these findings show that CGI-58 regulates hepatic neutral lipid storage and inflammation in the genetic absence of ATGL, demonstrating that mechanisms driving TAG lipolysis in hepatocytes differ significantly from those in adipocytes