Nkx2-5 and Sarcospan genetically interact in the development of the muscular ventricular septum of the heart

The muscular ventricular septum separates the flow of oxygenated and de-oxygenated blood in air-breathing vertebrates. Defects within it, termed muscular ventricular septal defects (VSDs), are common, yet less is known about how they arise than rarer heart defects. Mutations of the cardiac transcription factor NKX2-5 cause cardiac malformations, including muscular VSDs. We describe here a genetic interaction between Nkx2-5 and Sarcospan (Sspn) that affects the risk of muscular VSD in mice. Sspn encodes a protein in the dystrophin-glycoprotein complex. Sspn knockout (Sspn(KO)) mice do not have heart defects, but Nkx2-5(+/−)/Sspn(KO) mutants have a higher incidence of muscular VSD than Nkx2-5(+/−) mice. Myofibers in the ventricular septum follow a stereotypical pattern that is disrupted around a muscular VSD. Subendocardial myofibers normally run in parallel along the left ventricular outflow tract, but in the Nkx2-5(+/−)/Sspn(KO) mutant they commonly deviate into the septum even in the absence of a muscular VSD. Thus, Nkx2-5 and Sspn act in a pathway that affects the alignment of myofibers during the development of the ventricular septum. The malalignment may be a consequence of a defect in the coalescence of trabeculae into the developing ventricular septum, which has been hypothesized to be the mechanistic basis of muscular VSDs

Preservation of geochemical characteristics in Permo-Triassic mudstones by metagenesis and low-grade metamorphism in the Tethys Himalaya, Central Nepal

Abstract HKT-ISTP 2013 A

Compromised Mitochondrial Protein Import Acts as a Signal for UPRmt

The induction of the mitochondrial unfolded protein response (UPRmt) results in increased transcription of the gene encoding the mitochondrial chaperone HSP70. We systematically screened the C. elegans genome and identified 171 genes that, when knocked down, induce the expression of an hsp-6 HSP70 reporter and encode mitochondrial proteins. These genes represent many, but not all, mitochondrial processes (e.g., mitochondrial calcium homeostasis and mitophagy are not represented). Knockdown of these genes leads to reduced mitochondrial membrane potential and, hence, decreased protein import into mitochondria. In addition, it induces UPRmt in a manner that is dependent on ATFS-1 but that is not antagonized by the kinase GCN-2. We propose that compromised mitochondrial protein import signals the induction of UPRmt and that the mitochondrial targeting sequence of ATFS-1 functions as a sensor for this signal

Why do women not use antenatal services in low and middle income countries? A metasynthesis of qualitative studies

Background: Almost 50% of women in low & middle income countries (LMIC’s) don’t receive adequate antenatal care. Women’s views can offer important insights into this problem. Qualitative studies exploring inadequate use of antenatal services have been undertaken in a range of countries, but the findings are not easily transferable. We aimed to inform the development of future antenatal care programmes through a synthesis of findings in all relevant qualitative studies. Methods and Findings: Using a pre-determined search strategy, we identified robust qualitative studies reporting on the views and experiences of women in LMIC’s who received inadequate antenatal care. We used meta-ethnographic techniques to generate themes and a line of argument synthesis. We derived policy relevant hypotheses from the findings. We included 21 papers representing the views of more than 1230 women from 15 countries. Three key themes were identified: ‘Pregnancy as socially risky and physiologically healthy’; ‘Resource use and survival in conditions of extreme poverty’and ‘Not getting it right first time’. The line of argument synthesis describes a dissonance between programme design and cultural contexts that may restrict access and discourage return visits. We hypothesize that centralized, risk-focused antenatal care programmes may be at odds with the resources, beliefs and experiences of pregnant women who underuse antenatal services. Conclusions: Our findings suggest that there may be a mis-alignment between current antenatal provision and the social and cultural context of some women in LMIC’s. Antenatal care provision that is theoretically and contextually at odds with local contextual beliefs and experiences are likely to be underused, especially when attendance generates increased personal risks of lost family resource or physical danger during travel; when the promised care is not delivered due to resource constraints; and when women experience covert or overt abuse in care settings

Big Food, Food Systems, and Global Health

In an article that forms part of the PLoS Medicine series on Big Food, guest editors David Stuckler and Marion Nestle lay out why more examination of the food industry is necessary, and offer three competing views on how public health professionals might engage with Big Food

Effectiveness of the Local Adaptation Plan of Action to support climate change adaptation in Nepal

A key challenge in climate change adaptation in developing countries as a whole, and to handling global change in particular, is to link local adaptation needs on the one hand, with national adaptation initiatives on the other, so that vulnerable households and communities can directly benefit. This study assesses the impact of the Nepal government’s efforts to promote its Local Adaptation Plan of Action (LAPA) and its applicability to other least developed countries (LDCs). Based on data gathered from two field studies in Nepal, the research shows that the Nepal’s LAPA has succeeded in mobilizing local institutions and community groups in adaptation planning and recognizing their role in adaptation. However, the LAPA approach and implementation have been constrained by sociostructural and governance barriers that have failed to successfully integrate local adaptation needs in local planning and increase the adaptive capacity of vulnerable households. This paper describes the mechanisms of suitable governance strategies for climate change adaptation specific to Nepal and other LDCs. It also argues the need to adopt an adaptive comanagement approach, where the government and all stakeholders identify common local- and national-level mainstreaming strategy for knowledge management, resource mobilization, and institutional development, ultimately using adaptation as a tool to handle global change

Introduction: Human ecology in the Himalaya

Knowledge of human adaptation in the Himalayas has developed more slowly than that for other world mountain systems. At the same time, the opening of the region to research has focused attention toward description in a “natural history” mode until quite recently. Where these studies have addressed issues of adaptation they have tended to do so more as a heuristic tool rather than in terms of contributing to the development of adaptive perspectives from a uniquely Himalayan vantage point. The contributions to this special issue suggest some of Himalayan cultural ecology's new themes as it more directly assumes a truly processual approach that incorporates the individual and domestic dimensions of adaptation within historical and social contexts .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44482/1/10745_2004_Article_BF00889710.pd

Understanding the consumption of folic acid during preconception, among Pakistani, Bangladeshi and white British mothers in Luton, UK: a qualitative study

Background To review the similarities and differences in Pakistani, Bangladeshi and White British mothers health beliefs (attitudes, knowledge and perceptions) and health behaviour regarding their consumption of folic acid pre-conception, to reduce the risk of neural tube defects. Methods Our study used a descriptive qualitative research approach, implementing face-to-face focus group discussions with Pakistani, Bangladeshi or White British mothers (normal birth outcomes and mothers with poor birth outcomes) and semi-structured interviews or focus groups with service providers using semi-structured topic guides. This method is well suited for under researched areas where in-depth information is sought. There were three sample groups: 1. Pakistani, Bangladeshi and White British mothers with normal birth outcomes (delivery after 37 weeks of gestation, in the preceding 6 to 24 months, weighing 2500 g and living within a specified postcode area in Luton, UK). 2. Pakistani Bangladeshi and white British bereaved mothers who had suffered a perinatal mortality (preceding 6 to 24 months, residing within a specificied postcode area). 3. Healthcare professionals working on the local maternity care pathway (i.e. services providing preconception, antenatal, antepartum and postpartum care). Transcribed discussions were analysed using the Framework Analysis approach. Results The majority of mothers in this sample did not understand the benefits or optimal time to take folic acid pre-conception. Conversely, healthcare professionals believed the majority of women did consume folic acid, prior to conception. Conclusions There is a need to increase public health awareness of the optimal time and subsequent benefits for taking folic acid, to prevent neural tube defects.</p