Lamin A Δexon9 mutation leads to telomere and chromatin defects but not genomic instability

Over 300 mutations in the LMNA gene, encoding A-type lamins, are associated with 15 human degenerative disorders and premature aging syndromes. Although genomic instability seems to contribute to the pathophysiology of some laminopathies, there is limited information about what mutations cause genomic instability and by which molecular mechanisms. Mouse embryonic fibroblasts depleted of A-type lamins or expressing mutants lacking exons 8–11 (Lmna(Δ8–11/Δ8–11)) exhibit alterations in telomere biology and DNA repair caused by cathepsin L-mediated degradation of 53BP1 and reduced expression of BRCA1 and RAD51. Thus, a region encompassing exons 8–11 seems essential for genome integrity. Given that deletion of lamin A exon 9 in the mouse (Lmna(Δ9/Δ9)) results in a progeria phenotype, we tested if this domain is important for genome integrity. Lmna(Δ9/Δ9) MEFs exhibit telomere shortening and heterochromatin alterations but do not activate cathepsin L-mediated degradation of 53BP1 and maintain expression of BRCA1 and RAD51. Accordingly, Lmna(Δ9/Δ9) MEFs do not present genomic instability, and expression of mutant lamin A Δexon9 in lamin-depleted cells restores DNA repair factors levels and partially rescues nuclear abnormalities. These data reveal that the domain encoded by exon 9 is important to maintain telomere homeostasis and heterochromatin structure but does not play a role in DNA repair, thus pointing to other exons in the lamin A tail as responsible for the genomic instability phenotype in Lmna(Δ8–11/Δ8–11) mice. Our study also suggests that the levels of DNA repair factors 53BP1, BRCA1 and RAD51 could potentially serve as biomarkers to identify laminopathies that present with genomic instability

Pregnancy and Fetal Outcomes After Exposure to Mefloquine in the Pre- and Periconception Period and During Pregnancy

Pregnant women who travel to malarious areas and their clinicians need data on the safety of malaria chemoprophylaxis. The drug safety database analysis of mefloquine exposure in pregnancy showed that the birth defect prevalence and fetal loss in maternal, prospectively-monitored cases were comparable to background rate

Estimating above ground net biomass change in tropical and subtropical forests: refinement of IPCC default values using forest plot data

As countries advance in greenhouse gas (GHG) accounting for climate change mitigation, consistent estimates of above ground biomass (AGB) net change are needed for the tropics and subtropics. Countries with limited forest monitoring capabilities rely on 2006 IPCC default AGB net change values, which are averages per ecological zone, per continent. These previous defaults come from single studies, provide no uncertainty indications, and aggregate old secondary forests and old-growth forests. In this study, we update these default values using forest plot data. In comparison with previous estimates, new values include data published from 2006 onwards, are derived from multiple sites per global ecological zone, provide measures of variation, and divide forests >20 years old into older secondary forests and old-growth forests. We compiled 176 AGB chronosequences in secondary forests and AGB net change rates from 536 permanent plots in old-growth and managed or logged forests. In this dataset, across all continents and ecozones, AGB net change rates in younger secondary forests (go years) are higher than rates in older secondary (>20 years and ≤100 years) forests and managed or logged forests, which in turn are higher than rates in old-growth forests (> 100 years). Data availability is highest for North and South America, followed by Asia then Africa. We provide a rigorous and traceable refinement of the IPCC 2006 AGB net change default rates, identify which areas in the tropics and subtropics require more research on AGB change, and reflect on possibilities for improvement as more data becomes available

A systematic review on health resilience to economic crises

Background The health effects of recent economic crises differ markedly by population group. The objective of this systematic review is to examine evidence from longitudinal studies on factors influencing resilience for any health outcome or health behaviour among the general population living in countries exposed to financial crises. Methods We systematically reviewed studies from six electronic databases (EMBASE, Global Health, MEDLINE, PsycINFO, Scopus, Web of Science) which used quantitative longitudinal study designs and included: (i) exposure to an economic crisis; (ii) changes in health outcomes/behaviours over time; (iii) statistical tests of associations of health risk and/or protective factors with health outcomes/behaviours. The quality of the selected studies was appraised using the Quality Assessment Tool for Quantitative Studies. PRISMA reporting guidelines were followed. Results From 14,584 retrieved records, 22 studies met the eligibility criteria. These studies were conducted across 10 countries in Asia, Europe and North America over the past two decades. Ten socio-demographic factors that increased or protected against health risk were identified: gender, age, education, marital status, household size, employment/occupation, income/ financial constraints, personal beliefs, health status, area of residence, and social relations. These studies addressed physical health, mortality, suicide and suicide attempts, mental health, and health behaviours. Women’s mental health appeared more susceptible to crises than men’s. Lower income levels were associated with greater increases in cardiovascular disease, mortality and worse mental health. Employment status was associated with changes in mental health. Associations with age, marital status, and education were less consistent, although higher education was associated with healthier behaviours. Conclusions Despite widespread rhetoric about the importance of resilience, there was a dearth of studies which operationalised resilience factors. Future conceptual and empirical research is needed to develop the epidemiology of resilience

Ocurrencia natural del hiperparásito Ampelomyces quisqualis (Ascomycota, Phaeosphaeriaceae) en ambientes urbanos de Tucumán (Argentina)

Platanus × acerifolia es usado como un árbol urbano de sombra a lo largo de Argentina. A finales del otoño e invierno del 2023, las hojas y frutos de P. × acerifolia que mostraban los típicos síntomas de un mildiú pulverulento, se recolectaron en las principales calles de Tucumán, Argentina. Basados en su morfología y comparando con descripciones disponibles, el hongo fue identificado como la forma asexual de Erysiphe platani. Los especímenes estaban fuertemente hiperparasitados por Ampelomyces quisqualis, un ascomicete micoparásito usado como controlador biológico natural del desarrollo de especies de mildiú pulverulento. Este trabajo reporta la ocurrencia natural de Ampelomyces en ambientes urbanos de Argentina. Se describen e ilustran los síntomas de la enfermedad y las características morfológicas del anamorfo y el micoparásito.Platanus × acerifolia is used as an urban shade tree in many cities throughout Argentina.In late autumn and winter of 2023, leaves and fruits of P. × acerifolia showingtypical symptoms of a powdery mildew were collected along the main streets ofTucumán, Argentina. Its morphology and comparison with published descriptionsallowed us to identify the fungus as the asexual morph of Erysiphe platani. Thespecimens were heavily hyperparasitized by Ampelomyces quisqualis, a mycoparasiticascomycete, used as a natural biological control of the development of powderymildew species. This work reports the natural occurrence of Ampelomyces in urbanenvironments in Argentina. The disease symptoms and morphological characteristicsof the powdery mildew anamorph and the mycoparasite are described and illustrated.Fil: Castillo, Lucas A.. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Suarez, Guillermo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentin

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201