123 research outputs found

    Exploring Niches for Short-Season Grain Legumes in Semi-Arid Eastern Kenya — Coping with the Impacts of Climate Variability

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    Climate variability is the major risk to agricultural production in semi-arid agroecosystems and the key challenge to sustain farm livelihoods for the 500 million people who inhabit these areas worldwide. Short-season grain legumes have great potential to address this challenge and help to design more resilient and productive farming systems. However, grain legumes display a great diversity and differ widely in growth, development, and resource use efficiency. Three contrasting short season grain legumes common bean (Phaseolus vulgaris L.), cowpea (Vigna unguiculata (L.) Walp.] and lablab [Lablab purpureus (L.) Sweet] were selected to assess their agricultural potential with respect to climate variability and change along the Machakos-Makueni transect in semi-arid Eastern Kenya. This was undertaken using measured data [a water response trial conducted during 2012/13 and 2013/14 in Machakos, Kenya] and simulated data using the Agricultural Production System sIMulator (APSIM). The APSIM crop model was calibrated and validated to simulate growth and development of short-season grain legumes in semi-arid environments. Water use efficiency (WUE) was used as indicator to quantify the production potential. The major traits of adaptation include early flowering and pod and seed set before the onset of terminal drought. Early phenology together with adapted canopy architecture allowed more optimal water use and greater partitioning of dry matter into seed (higher harvest index). While common bean followed a comparatively conservative strategy of minimizing water loss through crop transpiration, the very short development time and compact growth habit limited grain yield to rarely exceed 1,000 kg ha−1. An advantage of this strategy was relatively stable yields independent of in-crop rainfall or season length across the Machakos-Makueni transect. The growth habit of cowpea in contrast minimized water loss through soil evaporation with rapid ground cover and dry matter production, reaching very high grain yields at high potential sites (3,000 kg ha−1) but being highly susceptible to in-season drought. Lablab seemed to be best adapted to dry environments. Its canopy architecture appeared to be best in compromising between the investment in biomass as a prerequisite to accumulate grain yield by minimizing water loss through soil evaporation and crop transpiration. This lead to grain yields of up to 2,000 kg ha−1 at high potential sites and >1,000 kg ha−1 at low potential sites. The variance of observed and simulated WUE was high and no clear dependency on total rainfall alone was observed for all three short-season grain legumes, highlighting that pattern of water use is also important in determining final WUEbiomass and WUEgrain. Mean WUEgrain was lowest for cowpea (1.5–3.5 kggrain ha−1 mm−1) and highest for lablab (5–7 kggrain ha−1 mm−1) reflecting the high susceptibility to drought of cowpea and the good adaptation to dry environments of lablab. Results highlight that, based on specific morphological, phonological, and physiological characteristics, the three short-season grain legumes follow different strategies to cope with climate variability. The climate-smart site-specific utilization of the three legumes offers promising options to design more resilient and productive farming systems in semi-arid Eastern Kenya

    A case-control study of GST polymorphisms and arsenic related skin lesions

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    BACKGROUND: Polymorphisms in GSTT1, GSTM1 and GSTP1 impact detoxification of carcinogens by GSTs and have been reported to increase susceptibility to environmentally related health outcomes. Individual factors in arsenic biotransformation may influence disease susceptibility. GST activity is involved in the metabolism of endogenous and exogenous compounds, including catalyzing the formation of arsenic-GSH conjugates. METHODS: We investigated whether polymorphisms in GSTT1, GSTP1 and GSTM1 were associated with risk of skin lesions and whether these polymorphisms modify the relationship between drinking water arsenic exposure and skin lesions in a case control study of 1200 subjects frequency matched on age and gender in community clinics in Pabna, Bangladesh in 2001–2002. RESULTS AND DISCUSSION: GSTT1 homozygous wildtype status was associated with increased odds of skin lesions compared to the null status (OR1.56 95% CI 1.10–2.19). The GSTP1 GG polymorphism was associated with greater odds of skin lesions compared to GSTP1 AA, (OR 1.86 (95%CI 1.15–3.00). No evidence of effect modification by GSTT1, GSTM1 or GSTP1 polymorphisms on the association between arsenic exposure and skin lesions was detected. CONCLUSION: GSTT1 wildtype and GSTP1 GG are associated with increased risk of skin lesions

    An Atlas of the Thioredoxin Fold Class Reveals the Complexity of Function-Enabling Adaptations

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    The group of proteins that contain a thioredoxin (Trx) fold is huge and diverse. Assessment of the variation in catalytic machinery of Trx fold proteins is essential in providing a foundation for understanding their functional diversity and predicting the function of the many uncharacterized members of the class. The proteins of the Trx fold class retain common features—including variations on a dithiol CxxC active site motif—that lead to delivery of function. We use protein similarity networks to guide an analysis of how structural and sequence motifs track with catalytic function and taxonomic categories for 4,082 representative sequences spanning the known superfamilies of the Trx fold. Domain structure in the fold class is varied and modular, with 2.8% of sequences containing more than one Trx fold domain. Most member proteins are bacterial. The fold class exhibits many modifications to the CxxC active site motif—only 56.8% of proteins have both cysteines, and no functional groupings have absolute conservation of the expected catalytic motif. Only a small fraction of Trx fold sequences have been functionally characterized. This work provides a global view of the complex distribution of domains and catalytic machinery throughout the fold class, showing that each superfamily contains remnants of the CxxC active site. The unifying context provided by this work can guide the comparison of members of different Trx fold superfamilies to gain insight about their structure-function relationships, illustrated here with the thioredoxins and peroxiredoxins

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    The Problematization of Sexuality among Women Living with HIV and a New Feminist Approach for Understanding and Enhancing Women’s Sexual Lives

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    In the context of HIV, women’s sexual rights and sexual autonomy are important but frequently overlooked and violated. Guided by community voices, feminist theories, and qualitative empirical research, we reviewed two decades of global quantitative research on sexuality among women living with HIV. In the 32 studies we found, conducted in 25 countries and composed mostly of cis-gender heterosexual women, sexuality was narrowly constructed as sexual behaviours involving risk (namely, penetration) and physiological dysfunctions relating to HIV illness, with far less attention given to the fullness of sexual lives in context, including more positive and rewarding experiences such as satisfaction and pleasure. Findings suggest that women experience declines in sexual activity, function, satisfaction, and pleasure following HIV diagnosis, at least for some period. The extent of such declines, however, is varied, with numerous contextual forces shaping women’s sexual well-being. Clinical markers of HIV (e.g., viral load, CD4 cell count) poorly predicted sexual outcomes, interrupting widely held assumptions about sexuality for women with HIV. Instead, the effects of HIV-related stigma intersecting with inequities related to trauma, violence, intimate relations, substance use, poverty, aging, and other social and cultural conditions primarily influenced the ways in which women experienced and enacted their sexuality. However, studies framed through a medical lens tended to pathologize outcomes as individual “problems,” whereas others driven by a public health agenda remained primarily preoccupied with protecting the public from HIV. In light of these findings, we present a new feminist approach for research, policy, and practice toward understanding and enhancing women’s sexual lives—one that affirms sexual diversity; engages deeply with society, politics, and history; and is grounded in women’s sexual rights

    Efficacy of self-monitored blood pressure, with or without telemonitoring, for titration of antihypertensive medication (TASMINH4): an unmasked randomised controlled trial.

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    BACKGROUND: Studies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care. METHODS: This study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mm Hg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisation was by a secure web-based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pressure at 12 months from randomisation. Primary analysis was of available cases. The trial is registered with ISRCTN, number ISRCTN 83571366. FINDINGS: 1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 [SD 16·7] mm Hg and telemonitoring, 136·0 [16·1] mm Hg vs usual care, 140·4 [16·5]; adjusted mean differences vs usual care: self-monitoring alone, -3·5 mm Hg [95% CI -5·8 to -1·2]; telemonitoring, -4·7 mm Hg [-7·0 to -2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference -1·2 mm Hg [95% CI -3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups. INTERPRETATION: Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care. FUNDING: National Institute for Health Research via Programme Grant for Applied Health Research (RP-PG-1209-10051), Professorship to RJM (NIHR-RP-R2-12-015), Oxford Collaboration for Leadership in Applied Health Research and Care, and Omron Healthcare UK
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