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Nutrient availability is a key determinant of tumor cell behavior. While nutrient‐rich conditions favor proliferation and tumor growth, scarcity, and particularly glutamine starvation, promotes cell dedifferentiation and chemoresistance. Here, linking ribosome biogenesis plasticity with tumor cell fate, we uncover that the amino acid sensor general control non‐derepressible 2 (GCN2; also known as eIF‐2‐alpha kinase 4) represses the expression of the precursor of ribosomal RNA (rRNA), 47S, under metabolic stress. We show that blockade of GCN2 triggers cell death by an irremediable nucleolar stress and subsequent TP53‐mediated apoptosis in patient‐derived models of colon adenocarcinoma (COAD). In nutrient‐rich conditions, a cell‐autonomous GCN2 activity supports cell proliferation by stimulating 47S rRNA transcription, independently of the canonical integrated stress response (ISR) axis. Impairment of GCN2 activity prevents nuclear translocation of methionyl‐tRNA synthetase (MetRS), resulting in nucleolar stress, mTORC1 inhibition and, ultimately, autophagy induction. Inhibition of the GCN2–MetRS axis drastically improves the cytotoxicity of RNA polymerase I (RNA pol I) inhibitors, including the first‐line chemotherapy oxaliplatin, on patient‐derived COAD tumoroids. Our data thus reveal that GCN2 differentially controls ribosome biogenesis according to the nutritional context. Furthermore, pharmacological co‐inhibition of the two GCN2 branches and RNA pol I activity may represent a valuable strategy for elimination of proliferative and metabolically stressed COAD cells.

Abstract Sudan, a country located in northeastern Africa, is grappling with a profound health crisis resulting from the recent war that erupted on April 15, 2023. This conflict has inflicted significant damage on the country's health system, particularly through the destruction of healthcare infrastructure. Approximately 61% of health facilities have been destroyed, leaving only 16% operating optimally in Khartoum. Hospitals and clinics, vital for public health, have become targets of violence, exacerbating the challenges faced by the nation. The World Health Organization has noted the closure of roughly 16 hospitals since the start of the conflicts due to staff safety concerns as well as a shortage of hospital supplies, consumables, and medication. There has also been a gradual waning of donor support and resources allocated to address protracted crises and emergencies worldwide Sudan receives very little funding from donor organizations to maintain its healthcare system, which worsens the nation's general public health architecture. This makes the country vulnerable to serious challenges like disease outbreaks, starvation, infectious diseases, deteriorating health infrastructure, and mental health issues. To successfully reduce the severity of negative impacts on public health, the crisis must be ceased and facilities reopened. An emergency disease surveillance system for infectious diseases should be established, women and child health should be prioritized, and mental health awareness programs and services should be implemented. The global community must support the efforts to mitigate the devastating effects of this crisis. This article aims to highlight the critical impact of the recent war on Sudan's healthcare, advocating for urgent measures, including facility reopening, disease surveillance, and global support to mitigate devastating consequences.

Abstract The effects of density are key in determining population dynamics, since they can positively or negatively affect the fitness of individuals. These effects have great relevance for polyphagous insects for which immature stages develop within a single site of finite feeding resources. Drosophila suzukii is a crop pest that induces severe economic losses for agricultural production; however, little is known about the effects of density on its life‐history traits. In the present study, we (i) investigated the egg distribution resulting from females' egg‐laying strategy and (ii) tested the immediate (on immatures) and delayed (on adults) effects of larval density on emergence rate, development time, potential fecundity, and adult size. The density used varied in a range between 1 and 50 larvae. We showed that 44.27% of the blueberries used for the oviposition assay contained between 1 and 11 eggs in aggregates. The high experimental density (50 larvae) has no immediate effect in the emergence rate but has effect on larval developmental time. This trait was involved in a trade‐off with adult life‐history traits: The time of larval development was reduced as larval density increased, but smaller and less fertile females were produced. Our results clearly highlight the consequences of larval crowding on the juveniles and adults of this fly.

Abstract Genetic diversity and temperature increases associated with global climate change are known to independently influence population growth and extinction risk. Whether increasing temperature may influence the effect of genetic diversity on population growth, however, is not known. We address this issue in the model protist system Tetrahymena thermophila. We test the hypothesis that at temperatures closer to the species’ thermal optimum (i.e., the temperature at which population growth is maximal, or Topt), genetic diversity should have a weaker effect on population growth compared to temperatures away from the thermal optimum. To do so, we grew populations of T. thermophila with varying levels of genetic diversity at increasingly warmer temperatures and quantified their intrinsic population growth rate, r. We found that genetic diversity increases population growth at cooler temperatures, but that as temperature increases, this effect weakens. We also show that a combination of changes in the amount of expressed genetic diversity (G) in r, plastic changes in population growth across temperatures (E), and strong G × E interactions underlie this temperature effect. Our results uncover important but largely overlooked temperature effects that have implications for the management of small populations with depauperate genetic stocks in an increasingly warming world.

Whole genome and exome sequencing (WGS/WES) are the most popular next‐generation sequencing (NGS) methodologies and are at present often used to detect rare and common genetic variants of clinical significance. We emphasize that automated sequence data processing, management, and visualization should be an indispensable component of modern WGS and WES data analysis for sequence assembly, variant detection (SNPs, SVs), imputation, and resolution of haplotypes. In this manuscript, we present a newly developed findable, accessible, interoperable, and reusable (FAIR) bioinformatics‐genomics pipeline Java based Whole Genome/Exome Sequence Data Processing Pipeline (JWES) for efficient variant discovery and interpretation, and big data modeling and visualization. JWES is a cross‐platform, user‐friendly, product line application, that entails three modules: (a) data processing, (b) storage, and (c) visualization. The data processing module performs a series of different tasks for variant calling, the data storage module efficiently manages high‐volume gene‐variant data, and the data visualization module supports variant data interpretation with Circos graphs. The performance of JWES was tested and validated in‐house with different experiments, using Microsoft Windows, macOS Big Sur, and UNIX operating systems. JWES is an open‐source and freely available pipeline, allowing scientists to take full advantage of all the computing resources available, without requiring much computer science knowledge. We have successfully applied JWES for processing, management, and gene‐variant discovery, annotation, prediction, and genotyping of WGS and WES data to analyze variable complex disorders. In summary, we report the performance of JWES with some reproducible case studies, using open access and in‐house generated, high‐quality datasets.

Abstract The climate of the western Mediterranean was characterized by a strong precipitation gradient during the Holocene driven by atmospheric circulation patterns. The scarcity of terrestrial paleoclimate archives has precluded exploring this hydroclimate pattern during Marine Isotope Stages 5 to 3. Here we present stable carbon and oxygen isotope records from three flowstones from southeast Iberia, which show that Dansgaard/Oeschger events were associated with more humid conditions. This is in agreement with other records from the Iberian Peninsula, the Mediterranean, and western Europe, which all responded in a similar way to millennial‐scale climate variability in Greenland. This general increase in precipitation during Dansgaard/Oeschger events cannot be explained by any present‐day or Holocene winter atmospheric circulation pattern. Instead, we suggest that changes in sea surface temperature played a dominant role in determining precipitation amounts in the western Mediterranean.

Abstract Objective Post‐traumatic stress disorder (PTSD) is a chronic, disabling condition. Our main objective is to investigate the association between trait mindfulness and PTSD over a period of 54 months. The secondary objective is to provide an exhaustive description of PTSD trajectories after the Bataclan attack. Methods We designed a prospective cohort study of 133 subjects present in the Bataclan concert hall during the November 2015 terrorist attack in Paris, France. Data were recorded 6, 18, 30, and 54 months after the attack. The primary endpoint was evaluated using the PTSD Check List Scale. Trait mindfulness was measured by the 14‐item Freiburg Mindfulness Inventory. Results FMI scores were consistently, significantly, and negatively associated with PCL‐5 scores. Adjusted odds ratios were at 0.81 (6 months), 0.88 (18 months) 0.82 (30 months), and 0.81 (54 months). PTSD prevalence 6 months after the event was 77%; it remained at 41% after 54 months. PTSD status of subjects is fluctuating. Latent class analysis divided the cohort into 3 groups: 21% of subject who remained below PTSD threshold throughout, 30% who remained above throughout, and 49% who steadily reduced their PTSD scores over time. Conclusion In our cohort, mindfulness is negatively associated with PTSD. Mindfulness programs are designed to improve global resilience and treat anxiety and mood disorders. Further research is needed to investigate if improving trait mindfulness is possible and beneficial for patients suffering from PTSD.

Background HIV infection and depression are each associated with increased ischemic stroke risk. Whether depression is a risk factor for stroke within the HIV population is unknown. Methods and Results We analyzed data on 106 333 (33 528 HIV‐positive; 72 805 HIV‐negative) people who were free of baseline cardiovascular disease from an observational cohort of HIV‐positive people and matched uninfected veterans in care from April 1, 2003 through December 31, 2014. International Classification of Diseases, Ninth Revision (ICD‐9) codes from medical records were used to determine baseline depression and incident stroke. Depression occurred in 19.5% of HIV‐positive people. After a median of 9.2 years of follow‐up, stroke rates were highest among people with both HIV and depression and lowest among those with neither condition. In Cox proportional hazard models, depression was associated with an increased risk of stroke for HIV‐positive people after adjusting for sociodemographic characteristics and cerebrovascular risk factors (hazard ratio [HR], 1.18; 95% CI: 1.03–1.34; 0.014). The depression‐stroke relationship was attenuated by alcohol use disorders, cocaine use, and baseline antidepressant use, and unaffected by combined antiretroviral therapy use or individual antiretroviral agents. A numerically higher HR of depression on stroke was found among those younger than 60 years. Conclusions Depression is associated with an increased risk of stroke among HIV‐positive people after adjusting for sociodemographic characteristics, traditional cerebrovascular risk factors, and HIV‐specific factors. Alcohol use disorders, cocaine use, and baseline antidepressant use accounted for some of the observed stroke risk. Depression may be a novel, independent risk factor for ischemic stroke in HIV, particularly among younger people.

A reliable estimate of recharge is needed for the sustainable management of groundwater resources. Water stable isotope (δO and δH) profiles in the unsaturated zone are frequently used to quantify groundwater recharge based on the seasonality of water isotopic compositions in precipitation. A very simple approach consists of integrating the soil water content between peak values of soil water isotopic composition, typically corresponding to precipitation signatures from warm and cold seasons. When precipitation isotopic compositions are available, a conceptual surface water isotopes budget and lumped parameter dispersion model can be computed. These models were applied on two field sites with similar permeable soils with grass cover but contrasting recharge regimes and seasonality, one in the Paris Basin (France) with continuous recharge from autumn to spring and the other in the St. Lawrence Lowlands (Quebec, Canada) with episodic recharge in fall and after snowmelt. For the two sites, the peak-to-peak method and isotope surface budget led to comparable recharge intensities. At least at the Paris Basin site, evaporation was shown to slightly modify the average unsaturated zone and hence groundwater isotope composition. The proposed parameterization of isotope fractionation due to evaporation allows qualitative estimation of the fraction of evaporation, at least during the recharge seasons. In spite of its simplifications and limitations, the proposed parsimonious model can give estimates of recharge in a variety of sites even if they are not well characterized, as it benefits from the large availability of monthly isotopic compositions in precipitation.