234 research outputs found

    Isolation and characterisation of human telomeres

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    Impact of COVID‑19 on food security and diet quality in Chilanga District, Zambia

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    Introduction Food security and nutrition have been severely impacted during the COVID-19 pandemic, particularly in low- and middle-income countries (LMICs). We aimed to quantify the impacts of the pandemic on food security and diet diversity within Chilanga District in Zambia and identify target areas for high-impact social protection and safety net programs. Methods We conducted a cross-sectional study in Chilanga district immediately after the Omicron variant surge in February 2022. Diet quality and food security were assessed based on a household diet questionnaire and a Minimum Dietary Diversity-Women (MDD-W) score was calculated. A paired t-test was used to determine whether there was a statistically significant change in the MDD-W score and McNemar test was used to investigate the change in food security between the pre- and peri-COVID-19 period. Results Compared to the pre-COVID-19 period, there were increases in food prices across the board in the peri- COVID-19 period and decreased consumption of key food categories including legumes, dairy and vitamin A rich foods. Despite high rates of food insecurity, only 6.6% of surveyed households received any cash or in-kind assistance from a government agency, non-profit, or other organization in the post-COVID-19 period. Conclusion The COVID-19 pandemic had significant impacts on food security and dietary diversity in Chilanga district. This is particularly relevant in the low-income communities that we surveyed, which had pre-existing challenges with food security. Additional resources must be invested in Chilanga District and similarly affected areas to address this gap in access to food and promote national equity

    Undernutrition in older children and adolescents in peri-urban Zambia

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    Background: Adolescents make up roughly a quarter of the population in Zambia; however, most nutrition-related programming is targeted at the underfive population. Understanding the scale of undernutrition in older children and adolescents is fundamental to alleviating food insecurity and addressing undernutrition across all age groups. Methods: A cross-sectional survey was performed in four low-income, peri-urban compounds in Chilanga District which included anthropometric measurements of children between ages 6 months-19 years and a household-level diet diversity and food security questionnaire. Wasting was used for children under 5 and thinness for children 5–19 years. Descriptive analysis and multivariate logistic regression were conducted to quantify the prevalence and distribution of malnutrition and understand the impact of food security. Results: We surveyed 393 households and 1,004 children between the ages of 6 months and 19 years. Children aged 6–9 years had the highest prevalence of severe thinness (5.2%) and adolescents (10–19 years) had the highest rates of moderate thinness (6.5%). Across all age groups, more than 75% of children were in households that worried about running out of food in the previous month. 24.9% of adolescents and 28.4% of older children were in households were more likely to go a whole day without eating compared to 16.9% of children under 5. Conclusion: Our survey indicated that malnutrition in adolescents and older children living in Chilanga district was comparable to those under 5. Interventions to address undernutrition must be targeted at older children and adolescents in order to ameliorate this burden

    Undernutrition in older children and adolescents in peri-urban Zambia

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    Background: Adolescents make up roughly a quarter of the population in Zambia; however, most nutrition-related programming is targeted at the underfive population. Understanding the scale of undernutrition in older children and adolescents is fundamental to alleviating food insecurity and addressing undernutrition across all age groups. Methods: A cross-sectional survey was performed in four low-income, peri-urban compounds in Chilanga District which included anthropometric measurements of children between ages 6 months-19 years and a household-level diet diversity and food security questionnaire. Wasting was used for children under 5 and thinness for children 5–19 years. Descriptive analysis and multivariate logistic regression were conducted to quantify the prevalence and distribution of malnutrition and understand the impact of food security. Results: We surveyed 393 households and 1,004 children between the ages of 6 months and 19 years. Children aged 6–9 years had the highest prevalence of severe thinness (5.2%) and adolescents (10–19 years) had the highest rates of moderate thinness (6.5%). Across all age groups, more than 75% of children were in households that worried about running out of food in the previous month. 24.9% of adolescents and 28.4% of older children were in households were more likely to go a whole day without eating compared to 16.9% of children under 5. Conclusion: Our survey indicated that malnutrition in adolescents and older children living in Chilanga district was comparable to those under 5. Interventions to address undernutrition must be targeted at older children and adolescents in order to ameliorate this burden

    Diphthamide modification of eEF2 requires a J-domain protein and is essential for normal development

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    The intracellular target of diphtheria toxin is a modified histidine residue, diphthamide, in the translation elongation factor, eEF2. This enigmatic modification occurs in all eukaryotes, and is produced in yeast by the action of five gene products, DPH1 to DPH5. Sequence homologues of these genes are present in all sequenced eukaryotic genomes and in higher eukaryotes there is functional evidence for DPH1, 2, 3, and 5 acting in diphthamide biosynthesis. We have identified a mouse mutant in the remaining gene, Dph4. Cells derived from homozygous mutant embryos lack the diphthamide modification of EF2 and are resistant to killing by diphtheria toxin. Reporter-tagged DPH4 protein localizes to the cytoskeleton, in contrast to the localization of DPH1, and consistent with evidence that DPH4 is not part of a proposed complex containing DPH1, 2 and 3. Mice homozygous for the mutation are retarded in growth and development and almost always die before birth. Those that survive long enough have preaxial polydactyly, a duplication of digit 1 of the hind foot. This same defect is seen in embryos homozygous for mutation of DPH1, suggesting that lack of diphthamide on eEF2 could result in translational failure of specific proteins, rather than a generalized translation downregulation

    Genetic background modifies vulnerability to glaucoma related phenotypes in Lmx1b mutant mice

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    Variants in the LIM homeobox transcription factor 1-beta (LMX1B) gene predispose individuals to elevated intraocular pressure (IOP), a key risk factor for glaucoma. However, the effect of LMX1Bmutations varies widely between individuals. To better understand the mechanisms underlying LMX1B-related phenotypes and individual differences, we backcrossed the Lmx1bV265D (also known as Lmx1bIcst ) allele onto the C57BL/6J (B6), 129/Sj (129), C3A/BLiA-Pde6b+ /J (C3H) and DBA/2J-Gpnmb+ (D2-G) mouse strain backgrounds. Strain background had a significant effect on the onset and severity of ocular phenotypes in Lmx1bV265D/+ mutant mice. Mice of the B6 background were the most susceptible to developing abnormal IOP distribution, severe anterior segment developmental anomalies (including malformed eccentric pupils, iridocorneal strands and corneal abnormalities) and glaucomatous nerve damage. By contrast, Lmx1bV265D mice of the 129 background were the most resistant to developing anterior segment abnormalities, had less severe IOP elevation than B6 mutants at young ages and showed no detectable nerve damage. To identify genetic modifiers of susceptibility to Lmx1bV265D -induced glaucoma-associated phenotypes, we performed a mapping cross between mice of the B6 (susceptible) and 129 (resistant) backgrounds. We identified a modifier locus on Chromosome 18, with the 129 allele(s) substantially lessening severity of ocular phenotypes, as confirmed by congenic analysis. By demonstrating a clear effect of genetic background in modulating Lmx1b-induced phenotypes, providing a panel of strains with different phenotypic severities and identifying a modifier locus, this study lays a foundation for better understanding the roles of LMX1B in glaucoma with the goal of developing new treatments

    Filamin a regulates neural progenitor proliferation and cortical size through Wee1-dependent Cdk1 phosphorylation

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    Cytoskeleton-associated proteins play key roles not only in regulating cell morphology and migration but also in proliferation. Mutations in the cytoskeleton-associated gene filamin A (FlnA) cause the human disorder periventricular heterotopia (PH). PH is a disorder of neural stem cell development that is characterized by disruption of progenitors along the ventricular epithelium and subsequent formation of ectopic neuronal nodules. FlnA-dependent regulation of cytoskeletal dynamics is thought to direct neural progenitor migration and proliferation. Here we show that embryonic FlnA null mice exhibited a reduction in brain size, and decline in neural progenitor numbers over time. The drop in the progenitor population was not attributable to cell death or changes in premature differentiation, but to prolonged cell cycle duration. Suppression of FlnA led to prolongation of the entire cell cycle length, principally in M-phase. FlnA loss impaired degradation of cyclin b1-related proteins, thereby delaying the onset and progression through mitosis. We found that the cdk1 kinase Wee1 bound FlnA, demonstrated increased expression levels after loss of FlnA function, and was associated with increased phosphorylation of cdk1. Phosphorylation of cdk1 inhibited activation of the anaphase promoting complex degradation system, which was responsible for cyclin b1 degradation and progression through mitosis. Collectively, our results demonstrate a molecular mechanism whereby FlnA loss impaired G2 to M phase entry, leading to cell cycle prolongation, compromised neural progenitor proliferation, and reduced brain size

    Undernutrition in older children and adolescents in peri-urban Zambia

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    BackgroundAdolescents make up roughly a quarter of the population in Zambia; however, most nutrition-related programming is targeted at the under-five population. Understanding the scale of undernutrition in older children and adolescents is fundamental to alleviating food insecurity and addressing undernutrition across all age groups.MethodsA cross-sectional survey was performed in four low-income, peri-urban compounds in Chilanga District which included anthropometric measurements of children between ages 6 months-19 years and a household-level diet diversity and food security questionnaire. Wasting was used for children under 5 and thinness for children 5–19 years. Descriptive analysis and multivariate logistic regression were conducted to quantify the prevalence and distribution of malnutrition and understand the impact of food security.ResultsWe surveyed 393 households and 1,004 children between the ages of 6 months and 19 years. Children aged 6–9 years had the highest prevalence of severe thinness (5.2%) and adolescents (10–19 years) had the highest rates of moderate thinness (6.5%). Across all age groups, more than 75% of children were in households that worried about running out of food in the previous month. 24.9% of adolescents and 28.4% of older children were in households were more likely to go a whole day without eating compared to 16.9% of children under 5.ConclusionOur survey indicated that malnutrition in adolescents and older children living in Chilanga district was comparable to those under 5. Interventions to address undernutrition must be targeted at older children and adolescents in order to ameliorate this burden
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