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A Macroporous Cyclodextrin Monolith for Continuous Removal of Per- and Polyfluoroalkyl Substances from Water
Mixed-Length Multivariate Covalent Organic Framework for Combined Near-Infrared Photodynamic Therapy and Drug Delivery
Real-Space Quantitative Molecular Analysis at Single-Molecule Resolution
Electron-Rich Macrocycle-Based Metal–Organic Frameworks for Efficient Photocatalytic CO<sub>2</sub> Reduction
Transgenerational inheritance of diminished ovarian reserve triggered by prenatal propylparaben exposure in mice
Socioeconomic predictors of vulnerability to flood-induced displacement
Abstract Floods displace an average of 12 million people every year, and are responsible for 54% of all disaster-induced displacements. Displacement risk scales with the vulnerability of exposed populations, but this vulnerability is poorly understood at a global scale. Here we show that measures of human development and rural areas explain more of the variance of displacement vulnerability than income levels measured by gross domestic product. We combine global flood and displacement data to estimate vulnerability, as the ratio of displacement to exposure, for over 300 historical flood events. We find that this vulnerability varies by several orders of magnitude both between and within countries. A random forest regression shows that infant mortality rate and population density are among the most important predictors of displacement vulnerability at national level and within countries, respectively, highlighting the vulnerability of low-income and marginalized populations and of rural communities. Our results indicate that, rather than relying on overall economic development alone, targeted investments are needed to improve living conditions and coping capacities for the most vulnerable groups, particularly outside of large cities, and to prepare for increasing flood hazards due to climate change.
The potential bidirectional relationship between long COVID and menstruation
Abstract Women have reported menstrual changes following SARS-CoV-2 infection and variation in long COVID symptoms across the menstrual cycle. We examined (i) whether COVID is linked to abnormal uterine bleeding (AUB), (ii) if long COVID symptoms vary with the menstrual cycle, and (iii) potential underlying mechanisms. Here we show long COVID was associated with AUB in a UK population. When compared to those never infected (n = 9423), long COVID participants (n = 1048) reported increased menstrual volume, duration and intermenstrual bleeding, while those who recovered from acute COVID (n = 1,716) reported minimal menstrual disruption. Long COVID symptoms examined in 54 women across the menstrual cycle revealed that severity was highest during the perimenstrual and proliferative phases. Serum and endometrial analysis revealed higher serum 5α-dihydrotestosterone and lower endometrial androgen receptors in long COVID versus no COVID. Other ovarian hormones showed no significant differences. Serum cytokine profiling indicated increased menstrual inflammation with long COVID and immune cell aggregates were observed in menstrual endometrium. In conclusion, long COVID was associated with AUB but not impaired ovarian function. Differences in peripheral and endometrial inflammation may contribute to AUB and long COVID symptom severity. We anticipate our findings will instigate exploration of new therapeutic strategies for women with long COVID.
SARS-CoV-2 infection dynamics in a MHCI-mismatched lung transplant recipient
Abstract A 48-year-old patient underwent lung transplantation because of severe COVID-19, which aggravated his underlying interstitial lung disease, despite the presence of detectable SARS-CoV-2. Subsequently, the graft is re-infected early in the post-procedural phase, leading to viral persistence for more than five months. By analyzing viral evolution and effector immune response within the transplanted organ, we observe three main findings. First, virus evolution differs in the transplanted organ compared to that in the upper respiratory tract and is affected by monoclonal SARS-CoV-2-specific antibodies and molnupiravir. Second, we show the potential clinical relevance of T cell HLA restriction that may facilitate viral clearance in the upper respiratory tract compared to the ongoing viral replication in the HLA mismatch organ. Third, close monitoring and modulation of immunosuppressive and antiviral therapy enables viral clearance in a lung transplantation setting despite incomplete SARS-CoV-2 clearance prior to transplantation.
Transcriptional dynamics of the oligodendrocyte lineage and its regulation by the brain erythropoietin system
Gray matter correlates of childhood maltreatment lack replicability in a multi-cohort brain-wide association study
Abstract Childhood maltreatment effects on cerebral gray matter have been frequently discussed as a neurobiological pathway for depression. However, localizations are highly heterogeneous, and recent reports have questioned the replicability of mental health neuroimaging findings. Here, we investigate the replicability of gray matter correlates of maltreatment, measured retrospectively via the Childhood Trauma Questionnaire, across three large adult cohorts (total N = 3225). Pooling cohorts yields maltreatment-related gray matter reductions, with most extensive effects when not controlling for depression diagnosis (maximum partial R2 = .022). However, none of these effects significantly replicate across cohorts. Non-replicability is consistent across a variety of maltreatment subtypes and operationalizations, as well as subgroup analyses with and without depression, and stratified by sex. Results are furthermore consistent across a variety of gray matter operationalizations, including voxel-based morphometry and parcellation-based cortical and subcortical measures. In this work, we show that there is little evidence for the replicability of gray matter correlates of childhood maltreatment, when adequately controlling for psychopathology. This underscores the need to focus on replicability research in mental health neuroimaging.
A mesothelial differentiation gateway drives fibrosis
Evolutionary history of ponerine ants highlights how the timing of dispersal events shapes modern biodiversity
Harms of introduced large herbivores outweigh benefits to native biodiversity
Abstract Introduced species significantly impact native biodiversity worldwide, with extensive research on harms but relatively less focus on benefits. Here, using the IUCN Environmental Impact Classification for Alien Taxa (EICAT) and EICAT+ frameworks, we assess 2021 negative and positive impacts of introduced large mammalian herbivores globally. We show that negative impacts are more common, and of higher magnitude than positive impacts, i.e. affect populations, not only the performance of individuals. Native species on islands and at higher trophic level experience greater impacts. Reported impact magnitudes decline over time only for positive impacts. Most positive impacts are caused indirectly through changes in species interactions and ecosystem properties, often following negative impacts on native plants through herbivory and disturbance. We therefore advise caution regarding the intentional introduction of large mammalian herbivores for conservation purposes (rewilding, assisted colonization) without rigorous assessment of their impacts on native communities.
Q&A Translational Cancer Nanomedicine
Multicolor fate mapping of microglia reveals polyclonal proliferation, heterogeneity, and cell-cell interactions after ischemic stroke in mice
Abstract Microglial proliferation is a principal element of the inflammatory response to brain ischemia. However, the precise proliferation dynamics, phenotype acquisition, and functional consequences of newly emerging microglia are not yet understood. Using multicolor fate mapping and computational methods, we here demonstrate that microglia exhibit polyclonal proliferation in the ischemic lesion of female mice. The peak number of clones occurs at 14 days, while the largest clones are observed at 4 weeks post-stroke. Whole-cell patch-clamp recordings of microglia reveal a homogeneous acute response to ischemia with a pattern of outward and inward currents that evolves over time. In the resolution phase, 8 weeks post-stroke, microglial cells within one clone share similar membrane properties, while neighboring microglia from different clones display more heterogeneous electrophysiological profiles. Super-resolution microscopy and live-cell imaging unmask various forms of cell-cell interactions between microglial cells from different clones. Overall, this study demonstrates the polyclonal proliferation of microglia after cerebral ischemia and suggests that clonality contributes to their functional heterogeneity. Thus, targeting clones with specific functional phenotypes may have potential for future therapeutic modulation of microglia after stroke.
Warming induces unexpectedly high soil respiration in a wet tropical forest
Abstract Tropical forests are a dominant regulator of the global carbon cycle, exchanging more carbon dioxide with the atmosphere than any other terrestrial biome. Climate models predict unprecedented climatic warming in tropical regions in the coming decades; however, in situ field warming studies are severely lacking in tropical forests. Here we present results from an in situ warming experiment in Puerto Rico, where soil respiration responses to +4 oC warming were assessed half-hourly for a year. Soil respiration rates were 42-204% higher in warmed relative to ambient plots, representing some of the highest soil respiration rates reported for any terrestrial ecosystem. While respiration rates were significantly higher in the warmed plots, the temperature sensitivity (Q10) was 71.7% lower, pointing to a mechanistic shift. Even with reduced Q10, if observed soil respiration rates persist in a warmer world, the feedback to future climate could be considerably greater than previously predicted or observed.
Gephyrin filaments represent the molecular basis of inhibitory postsynaptic densities
Abstract The multifunctional protein gephyrin clusters inhibitory receptors at the postsynaptic membrane in the CNS. Gephyrin has been proposed to form the inhibitory postsynaptic density by liquid-liquid phase separation, involving a complex interplay between receptor binding and oligomerization via its conserved G- and E-domains. Here we show by single particle cryo-EM analysis that dimerization promotes the formation of gephyrin filaments in which two E-domain dimers are linked by Z-shaped interfaces formed between two subdomains II (SDII) of adjacent dimers. Deletion of SDII, introduction of two epilepsy-causing pathogenic variants, or neutralization of an opposing charge in the interface abolish the formation of filaments, in vitro phase separation, and synaptic receptor clustering in hippocampal neurons. In conclusion, this work identifies gephyrin E-domain filaments as the structural foundation underlying gephyrin both phase separation and receptor clustering at inhibitory postsynaptic densities.