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Effects of soil biofumigation on non-target springtails (Collembola) and earthworms (Opisthopora)

Locating a control of plant and ecosystem water fluxes deep in the leaf

Incidence and factors associated with central line-associated bloodstream infection in patients with chronic intestinal failure. A 20-year retrolective cohort

Background Type 3 Intestinal Failure (IF-3) is a chronic condition in which patients may require long-term Outpatient Intravenous Supplementation (OIS) to maintain hydration and nutrition, they are susceptible to catheter-related infectious complications. The present study aimed to determine the incidence of factors associated with central line-associated bloodstream infection (CLABSI) in patients with IF-3 on OIS. Methodology Retrolective cohort study of patients with IF-3 undergoing OIS treated at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, a national tertiary care and referral center in Mexico City, between 2004 and 2024. Sociodemographic, anthropometric, biochemical, clinical, and microbiological data, including isolated pathogens, were collected. Variables associated with CLABSI incidence were determined using Poisson regression analysis. Results Sixty patients were included, of which 31 (51.7%) were female and 29 (48.3%) were male. The mean age was 49.5 ± 18.1 years, and BMI was 19.8 ± 5.31 kg/m 2 . The primary pathophysiological mechanism of IF-3 was short bowel syndrome (n = 23 (38.3%)). Twenty-seven (45%) patients developed CLABSI, resulting in 36 events over 27,200 catheter days, with an incidence rate of 1.323 per 1,000 catheter days. Fifty-seven pathogens were isolated, the most frequent being Gram-negative bacteria (52.6%), specifically the Enterobacter cloacae complex (23.3%) and Klebsiella oxytoca (16.6%). Patients with intestinal stomas had a higher incidence of CLABSI (74% vs 48.4%; p = 0.039). Depression (IR 1.43; 95% CI 1.04–1.97, p = 0.028) was associated with a higher incidence of CLABSI. Conclusions The incidence rate of CLABSI was lower than reported in other studies in upper-middle-income countries. Depression and the presence of intestinal stomas may be associated with a higher risk of CLABSI, possibly through their impact on self-care and stress-inflammation pathways. These results underscore the importance of psychosocial and clinical factors in preventing CLABSI. Multicentre studies are needed to enhance external validity across diverse settings.

Uncovering the role of integrated stress in Alzheimer’s disease through single-cell and transcriptomic analysis

MET goes to the membrane—A new place for the “old” juvenile hormone receptor

Determinants of skilled birth attendant delivery among reproductive age women in Lesotho: A multilevel analysis of demographic and health survey data

Background Skilled birth attendant (SBA) delivery, defined as childbirth assisted by trained healthcare professionals such as doctors, midwives, and nurses, is a cornerstone of the World Health Organization’s Safe Motherhood Initiative to reduce maternal mortality. Despite high SBA coverage in Lesotho, maternal mortality remains elevated. This study aimed to assess the determinants of SBA delivery among reproductive-age women in Lesotho using the 2023–2024 Lesotho Demographic and Health Survey data. Methods A cross-sectional study design was applied using nationally representative data of 1,407 women aged 15–49 years. Multilevel logistic regression models were employed. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were reported, with p-values <0.05 considered statistically significant. Results Skilled birth attendant (SBA) coverage was 91.8%. Women aged 35–49 had 60% lower odds of SBA delivery (AOR = 0.40; 95% CI: 0.17, 0.95). Higher maternal education (primary: AOR = 1.47; 95% CI: 1.02, 4.90; secondary: AOR = 1.63; 95% CI: 1.12, 2.94; and tertiary: AOR = 3.88; 95% CI: 2.50, 5.20), wealthier households (AOR = 4.30; 95% CI: 1.10, 16.80), and age at first birth between 20–24 years (AOR = 3.74; 95% CI: 1.77, 7.89) were positively associated with SBA delivery. Women initiating ANC in the third trimester had 63% lower odds of SBA use (AOR = 0.37; 95% CI: 0.14, 0.99). Conclusion Despite high SBA coverage in Lesotho, disparities exist, particularly among older women and late ANC initiators. Targeted policies such as community-based health education programs, transport support for rural women, mobile health reminders, incentives for facility deliveries, and the deployment of skilled birth attendants in underserved areas are vital to improving access, promoting education, encouraging early ANC engagement, and ultimately enhancing SBA utilization to reduce maternal mortality.

Doping induced enhancement for acetone sensing in ceria

Competition between a transmembrane helix on Scap and a membrane cholesterol regulates Scap–Insig interaction and SREBP activation

Cholesterol homeostasis in mammalian cells relies on the interaction between two endoplasmic reticulum (ER) sterol-sensing membrane proteins, Scap and Insig. Their interaction regulates activation of transcription factors called sterol regulatory element–binding proteins (SREBPs) that control genes for cholesterol biosynthesis and uptake. Previous studies suggested a model where cholesterol sensing by Scap involves communication across the ER membrane between two functional domains, a cholesterol-binding domain on the luminal side and a COPII-binding domain on the cytosolic side. When ER cholesterol is low, Scap binds COPII adapter proteins to facilitate ER-to-Golgi transport and proteolytic activation of SREBPs. When ER cholesterol is above a threshold concentration, this transport is blocked, a process that requires Insigs. However, the precise molecular mechanisms by which cholesterol and Insigs control the conformations of Scap remain unknown. Here, we elucidate the 3.2 Å cryo-EM structure of a Scap/Insig complex in the presence of saturating amounts of cholesterol. Structure-guided mutagenesis of the Scap/Insig interface indicates that Scap’s transmembrane helix 7 (TM7) plays a critical role in transducing conformational changes between the luminal and cytosolic sides of the ER membrane to control Scap/SREBP transport from ER to Golgi. An intramembrane cholesterol bound at the Scap/Insig interface competes with the intramolecular interaction of Scap’s TM7 at this interface to modulate cholesterol sensing. These results further advance our understanding of how Scap senses cholesterol and provides additional targets for controlling cholesterol and lipid synthesis in the context of metabolic diseases and even some cancers.

Targeting ceramide metabolism to restore hypoxia-induced apoptosis in p53-deficient colon cancer cells

Hypoxic stress in solid tumors triggers growth arrest and apoptosis through p53 activation and stabilization. This environment inactivates p53 and drives the expansion of p53-mutant clones, which accentuate tumor aggressiveness. Ceramide, a signaling sphingolipid, was previously identified as a downstream collaborator with p53 in the stress-induced apoptosis and cell cycle arrest. Among sphingolipids, the balance between pro- and anti-apoptotic products, dictated by the expression and activity of appropriate enzymes, helps determine cell fate in response to hypoxia. The current study aimed to understand the role of ceramide in HCT116 human colon cancer cells response to hypoxia in the presence or absence of p53, and to determine whether the modulation of ceramide metabolism could sensitize the resistant p53-deficient cells to hypoxia-induced cell death. We observed that HCT116 p53-deficient cells were resistant to hypoxic cell death. We explored the role of ceramide in this response by screening for different sphingolipid metabolites through liquid-chromatography-mass spectrometry, and by measuring the expression of key enzymes involved in ceramide biosynthesis and breakdown. We also evaluated the changes in the cellular response to hypoxia associated with introduction of sphingolipid metabolites or with modulating the activity of related sphingolipid-metabolizing enzymes. In hypoxic p53-deficient cells, ceramide was synthesized via the de novo pathway through the action of ceramide synthases and dihydroceramide desaturase (DEGS1) driving the evasion of hypoxia-induced apoptosis. Among the accumulating ceramide species in p53 deficient cells, C24-ceramide was the most abundant and possibly contributing to their resistance. Tipping the sphingolipid balance in favor of pro-apoptotic sphingolipids, through the addition of C6 ceramide or sphingosine, or through the combined pharmacologic inhibition of DEGS1 and sphingosine kinase 1, helped circumvent the cellular resistance to hypoxia-induced apoptosis in cells lacking p53. Therefore, modulating sphingolipid metabolism may be a viable approach in the treatment of solid tumors with hypoxic regions.

A high resolution urban and rural settlement map of Africa using deep learning and satellite imagery

Abstract Accurate and consistent mapping of urban and rural areas is crucial for sustainable development, spatial planning, and policy design. It is particularly important in simulating the complex interactions between human activities and natural resources. Existing global urban-rural datasets such as such as GHSL-SMOD, GHS Degree of Urbanisation, and GRUMP are often spatially coarse, methodologically inconsistent, and poorly adapted to heterogeneous regions such as Africa, which limits their usefulness for policy and research. Their coarse grids and rule-based classification methods obscure small or informal settlements, and produce inconsistencies between countries. In this study, we develop a DeepLabV3-based deep learning framework that integrates multi-source data, including Landsat-8 imagery, VIIRS nighttime lights, ESRI Land Use Land Cover (LULC), and GHS-SMOD, to produce a 10 m resolution urban-rural map across the African continent from 2016 to 2022. The use of Landsat data also highlights the potential to extend this mapping approach historically, reaching back to the 1990s. The model employs semantic segmentation to capture fine-scale settlement morphology, and its outputs are validated using the Demographic and Health Surveys (DHS) dataset, which provides independent, survey-based urban-rural labels. The model achieves an overall accuracy of 65% and a Kappa coefficient of 0.47 at the continental scale, outperforming existing global products such as SMOD. The resulting High-Resolution Urban-Rural (HUR) dataset provides an open and reproducible framework for mapping human settlements, supporting UN Sustainable Development Goal (SDG) 11—Sustainable Cities and Communities—and enabling more context-aware analyses of Africa’s rapidly evolving settlement systems, which indirectly support other SDGs, such as SDG 1 (No Poverty), by distinguishing human settlement types. We release a continent-wide urban-rural dataset covering the period from 2016 to 2022, offering a new source for high-resolution settlement mapping in Africa.oxy_aqreply_end

Peptide-based covalent inhibitor of tubulin detyrosination promotes mesenchymal-to-epithelial transition in lung cancer cells

Detyrosination is a reversible posttranslational modification specific to α-tubulin, which has been implicated in cancer progression and invasiveness by promoting epithelial-to-mesenchymal transition. The members of the vasohibin family, VASH1 and VASH2, were previously identified as the first class of enzymes involved in catalyzing this modification. Here, we report the development of a covalent VASH inhibitor, which is characterized by high specificity and low toxicity. By combining the use of a new compound with molecular approaches in lung cancer cell lines, we find that tubulin detyrosination plays an important role in the maintenance of mesenchymal properties. We show that in the absence of VASH activity, collective cell migration and 3D spheroid formation are severely compromised. Moreover, we demonstrate that the observed phenotypes are caused by the accumulation of the important epithelial marker E-cadherin with simultaneous reduction in mesenchymal markers N-cadherin and vimentin. Taken together, our study establishes tubulin detyrosination as a promising target for the future development of anticancer treatment.

Retraction: NAD(P)H: Quinone oxidoreductase 1 deficiency conjoint with marginal vitamin C deficiency causes cigarette smoke induced myelodysplastic syndromes

Structural basis for diosgenin as an inverse agonist of retinoic acid receptor-related orphan receptor γ

Mass spectrometry footprinting reveals how kinetic stabilizers counteract transthyretin dynamics altered by pathogenic mutations

The aggregation of transthyretin (TTR) results in life-threatening transthyretin amyloidosis. Familial forms of the disease arise from point mutations that destabilize the TTR tetramer, leading to its dissociation and/or monomer unfolding and subsequent formation of amyloid fibrils. Small molecules that kinetically stabilize the native tetramer effectively inhibit this aggregation. Although over 300 X-ray crystal structures of TTR have been determined, these data refer to a static structure and do not capture the conformational effects of mutations and ligand binding. Here, we demonstrate that hydrogen–deuterium exchange (HDX) and fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry (MS) offer critical insights into the conformational dynamics associated with TTR amyloidogenic mutations and the binding of kinetic stabilizers. The results indicate that the design of TTR binders should consider the specific conformational traits of each TTR pathogenic variant. We propose that incorporating MS-based techniques into TTR drug discovery will expedite the development of effective pathology-specific aggregation inhibitors.

“I feel good… I knew that I would…”: The role of self in musical reward across cultures

Listening to music can be a rewarding experience for many. Research has shown that multiple factors influence musical reward including personality, age, and musical expertise. However, the role of culture in shaping musical reward remains underexplored. Most cross-cultural studies in music psychology have compared individuals from different countries. This study adopted a novel approach by examining self-construal, an individual-level explanation for cultural differences, in relation to musical rewards associated with favourite music across cultures. A cross-sectional online questionnaire was administered to 435 participants. Results from the multilevel regression analyses, using the two-dimensional model of self-construal, revealed that only within-region variation of interdependent and independent self-construals, not between-region variation of interdependence and independence, were positively associated with musical reward. Specifically, both self-construals were associated with emotion evocation and social reward, while independent self-construal was associated with musical seeking, mood regulation, and sensory-motor subtypes. When applying the eight-dimensional model of self-construal, distinct self-construal profiles emerged in relation to different musical reward subtypes, with the interdependent pole of connectedness to others positively associated with most subtypes except for emotion evocation reward. These findings provide preliminary evidence that self-construal influences the types of rewards experienced across cultures. In particular, one’s sense of self, whether construed as interdependent or independent, shapes the types of rewards experienced with favourite music. This study underscores the importance of incorporating specific cultural factors in cross-cultural research on musical reward. By examining self-construal, this work contributes to a more nuanced understanding of cultural diversity in music psychology.

Navigating population-level coancestry in forensic mixture analysis

How attention-like behavior emerges in an artificial neural network

Impact of MED12 mutation and CDK8 activity on uterine leiomyoma growth and response to gonadotropin-releasing hormone agonist treatment

MED12 exon 2 mutation is the most frequent mutation associated with uterine leiomyomas. MED12 wild-type leiomyomas have a higher growth potential than mutant leiomyomas, suggesting that the mutation limits leiomyoma growth. MED12 forms a complex with CDK8 and is involved in the phosphorylation of RNA polymerase II, playing a role in transcriptional regulation. However, its mechanism of action in leiomyoma growth is not clear. We aimed to clarify the relationship between MED12 mutation status, response to gonadotropin-releasing hormone (GnRH) agonist treatment, and CDK8 activity in leiomyomas. We also examined the effects of CDK8 inhibitors on primary cultured uterine leiomyoma cells. We classified 44 surgically removed uterine leiomyomas into four groups according to GnRH agonist use and MED12 mutation status. CDK8 was co-immunoprecipitated from leiomyoma tissue extracts using MED12 antibody to test its kinase activity in vitro , and the amount of phosphorylated substrate was measured. Cell proliferation and apoptosis of primary cultured MED12 wild-type leiomyoma cells were evaluated in the presence of a CDK8 inhibitor and sex steroid hormones. Of the 44 leiomyomas tested, 11 MED12 wild-type leiomyomas without preoperative GnRH agonist treatment had significantly higher CDK8 activity than nine GnRH agonist-treated MED12 wild-type leiomyomas and 15 leiomyomas with MED12 mutations without GnRH agonist treatment. Treatment of primary cultured MED12 wild-type cells with CDK8 inhibitors significantly inhibited cell growth and increased apoptosis. MED12 wild-type leiomyoma cells without GnRH agonist treatment showed high CDK8 activity, and inhibition of CDK8 activity suppressed cell growth in vitro .

Association of the novel remnant cholesterol inflammatory index with acute coronary syndrome risk in hospitalized patients with diabetes: a two-center study

Competition for heritable wealth, not cultural group selection, drives the evolution of monogamy

The decline of polygyny and the rise of monogamy among complex, stratified societies characterized by high wealth inequality present a long-standing puzzle in anthropology. Competing explanations suggest that monogamy either i) reduces reproductive inequality, fosters cooperation, and enhances success in intergroup competition, or ii) mitigates conflict over heritable wealth—especially land—under conditions of high social stratification and ecological constraints. Both frameworks are influenced by the history of Indo-European societies, where monogamy has long been normative and closely associated with land inheritance and state formation. However, normative monogamy is also found in many societies beyond this historical context. To evaluate these competing hypotheses, we formalized their causal structure and applied Bayesian phylogenetic multilevel models to a global sample of 186 societies. Our results show that monogamy is strongly associated with land privatization and, in some regions, with ecological or demographic proxies for land scarcity—supporting the view that competition over heritable wealth promotes monogamy globally. In contrast, support for the intergroup competition model is inconsistent: While it may explain monogamy in some language families, these dynamics do not extend to most societies in our sample. Our findings suggest that monogamy arose repeatedly under similar socioecological conditions and cannot be fully explained by theories based primarily on Indo-European history.