Browse Articles

Barriers to orthodox medical care of prostate cancer in Ghana

Integrating Pollutant registers for the climate change risk evaluation of industrial companies in Australia, Europe and North America

The changing relationship between racial identity and skin color in Brazil

In recent years, Brazil’s non-White (Brown and Black) population became a numerical majority for the first time since the 19th century. Although we know this change was mostly due to racial reclassification, we do not know how such changes are related to skin color, the primary marker of race in Brazil. Using data from six Latin American Public Opinion Project (LAPOP), or America’s Barometer, surveys from 2010 to 2023, we examine how changes in racial self-identification (White, Brown, or Black) are related to respondent skin color (light, medium, or dark). We ask how the association between self-identified race and skin color changed over the 13-y period and to what extent these trends varied by educational level. We found a “darkening” of racial identification over time, especially among those with medium and dark skin, who increasingly identified as Black. Brazilians with light skin increasingly identified as Brown, but this was partly explained by changes in interviewer reporting of skin color in the same period. We found only minor evidence that education level was related to changing racial classification over time. Our findings further understanding of recent trends in racial reclassification, which may reflect growing Black consciousness and the extension of racial quotas to both Brown and Black Brazilians in federal universities and public sector jobs.

Investigation of electrochromic performances of multicolor V2O5 devices fabricated at low processing temperature

Deletion of metal transporter Zip14 reduces major histocompatibility complex II expression in murine small intestinal epithelial cells

Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation. Elevated fecal lipocalin-2, calprotectin, IgG levels, and dysbiosis support the inflammatory phenotype. Here, we show through RNA-sequencing, using purified intestinal epithelial cells (IECs), that Zip14 deletion produces markedly reduced expression of major histocompatibility complex class II (MHCII) molecules and the master MHCII transactivator ( Ciita ). qPCR, western analysis, and immunohistochemistry confirmed loss of MHCII. Spectrofluorimetry with zinc probe FluoZin-3 showed reduced labile zinc in IECs from knockout mice. Chromatin immunoprecipitation assays, using Ciita antibody and IEC chromatin, suggest decreased transcription accounts for depressed expression of specific MHCII genes. Assay for Transposase-Accessible Chromatin (ATAC) sequencing (ATAC-seq) demonstrated that H2-Aa , H2-Ab1 and other MHCII genes result from chromatin remodeling yielding closed chromatin at regulatory regions of these genes. In agreement, ATAC-seq showed peak density of the chromosomal regulatory region of Ciita is consistent with down regulation of specific MHCII genes in IECs with Zip14 loss. Finally, dietary zinc supplementation of knockout mice and zinc supplementation of intestinal organoids with Zip14 deletion restored transcript levels. Taken together, our data suggest that cellular zinc delivery, via Zip14, is necessary for proper chromatin occupancy, required for normal MHCII expression and effective immune functions, and to preclude inflammatory disorders of the small intestine.

Significant reduction in Hepatitis B virus infections following 32 years of universal Hepatitis B vaccination as part of EPI, Thailand

Reply to Zhang et al.: Parallel vector memories are required to explain all behavioral data in navigating bumblebees

Multi-view knowledge representation learning for personalized news recommendation

Zoos must embrace animal death for education and conservation

Multi-objective optimization and algorithmic evaluation for EMS in a HRES integrating PV, wind, and backup storage

Abstract This manuscript focuses on optimizing a Hybrid Renewable Energy System (HRES) that integrates photovoltaic (PV) panels, wind turbines (WT), and various energy storage systems (ESS), including batteries, supercapacitors (SCs), and hydrogen storage. The system uses a multi-objective optimization strategy to balance power management, aiming to minimize costs and reduce the likelihood of loss of power supply probability (LPSP). Seven different algorithms are assessed to identify the most efficient one for achieving these objectives, with the goal of selecting the algorithm that best balances cost efficiency and system performance. The system is assessed across three operational scenarios: (1) when energy supply meets demand with help from backup systems, (2) when demand exceeds supply and energy storage systems are depleted, and (3) when energy generation surpasses demand and storage systems are full. The HBA-based optimization effectively manages energy flow and storage, ensuring grid stability and minimizing overcharging risks. This system offers a reliable and sustainable power supply for isolated microgrids, effectively managing energy production, storage, and distribution. The research sets a new benchmark for future studies in decentralized energy systems, particularly in balancing technical efficiency and economic feasibility.

Confined cell migration along extracellular matrix space in vivo

Collective migration of cancer cells is often interpreted using concepts derived from the physics of active matter, but the experimental evidence is mostly restricted to observations made in vitro. Here, we study collective invasion of metastatic cancer cells injected into the mouse deep dermis using intravital multiphoton microscopy combined with a skin window technique and three-dimensional quantitative image analysis. We observe a multicellular but low-cohesive migration mode characterized by rotational patterns which self-organize into antiparallel persistent tracks with orientational nematic order. We analyze the deformations induced by the cells in the extracellular matrix and find broadly distributed strain bands with a prevalence of compression. A model of active nematic hydrodynamics is able to describe several statistical features of the experimentally observed flow, suggesting that collective cancer cell invasion can be interpreted as a nematic active fluid in the turbulent regime. Our results help elucidate the migration patterns of cancer cells in vivo and provide quantitative guidance for the development of realistic in vitro and in silico models for collective cell migration.

Maternal iron deficiency assessed by serum ferritin and birth outcomes in mainland China

Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction

Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects. We postulated that inhibition of GABA’s degradation enzyme, GABA aminotransferase (GABA-AT), would increase endogenous GABA levels and produce analgesia. We evaluated antinociceptive efficacy of the potent GABA-AT inhibitor OV329 in rodent models of neuropathic and inflammatory pain and assessed possible side effects (i.e., reward and motor impairment). OV329 attenuated the development and maintenance of mechanical and cold hypersensitivities induced by the chemotherapeutic agent paclitaxel. Prophylactic OV329, administered systemically, normalized paclitaxel-induced increases in glutamate levels and suppressed neuropathic nociception. Intrathecal OV329 suppressed paclitaxel-induced mechanical hypersensitivity, elevating GABA, and reducing glutamate levels in the lumbar spinal cord, consistent with a spinal site of action. Furthermore, OV329 largely synergized with paclitaxel to enhance 4T1 tumor cell line cytotoxicity without altering viability of nontumor cells. OV329 also attenuated inflammation-induced mechanical hypersensitivity induced by intraplanar injection of complete Freund’s adjuvant (CFA) with efficacy comparable to morphine. Unlike morphine, OV329 did not produce reward in a conditioned place preference assay in mice and was not self-administered intravenously by rats. Antinociceptive efficacy of OV329 was observed at doses that did not impair motor function or produce tolerance following chronic dosing. Thus, inhibition of GABA-AT with OV329 represents a unique therapeutic strategy to alleviate neuropathic and inflammatory pain with no apparent abuse liability, potentially producing a beneficial spectrum of pharmacological effects through enzymatic regulation.

Retinal ganglion cells encode the direction of motion outside their classical receptive field

Retinal ganglion cells (RGCs) typically respond to light stimulation over their spatially restricted receptive field. Using large-scale recordings in the mouse retina, we show that a subset of non- direction-selective (DS) RGCs exhibit asymmetric activity, selective to motion direction, in response to a stimulus crossing an area far beyond the classic receptive field. The extraclassical response arises via inputs from an asymmetric distal zone and is enhanced by desensitization mechanisms and an inherent DS component, creating a network of neurons responding to motion toward the optic disc. Pharmacological manipulations revealed the necessity of glycinergic amacrine cells for this response. Using in vivo recordings, we identified similar extraclassical responses in lateral geniculate nucleus neurons, suggesting such non conventional DS information is transferred to downstream structures. Our results suggest a complex integration of motion direction processing across the visual field, which arises beyond the classical receptive field boundaries.

Chromatin enables precise and scalable gene regulation with factors of limited specificity

Biophysical constraints limit the specificity with which transcription factors (TFs) can target regulatory DNA. While individual nontarget binding events may be low affinity, the sheer number of such interactions could present a challenge for gene regulation by degrading its precision or possibly leading to an erroneous induction state. Chromatin can prevent nontarget binding by rendering DNA physically inaccessible to TFs, at the cost of energy-consuming remodeling orchestrated by pioneer factors (PFs). Under what conditions and by how much can chromatin reduce regulatory errors on a global scale? We use a theoretical approach to compare two scenarios for gene regulation: one that relies on TF binding to free DNA alone and one that uses a combination of TFs and chromatin-regulating PFs to achieve desired gene expression patterns. We find, first, that chromatin effectively silences groups of genes that should be simultaneously OFF, thereby allowing more accurate graded control of expression for the remaining ON genes. Second, chromatin buffers the deleterious consequences of nontarget binding as the number of OFF genes grows, permitting a substantial expansion in regulatory complexity. Third, chromatin-based regulation productively co-opts nontarget TF binding for ON genes in order to establish a “leaky” baseline expression level, which targeted activator or repressor binding subsequently up- or down-modulates. Thus, on a global scale, using chromatin simultaneously alleviates pressure for high specificity of regulatory interactions and enables an increase in genome size with minimal impact on global expression error.

Electrochemical NAD+ regeneration in bacterial organelles

The 1831 CE mystery eruption identified as Zavaritskii caldera, Simushir Island (Kurils)

Polar ice cores and historical records evidence a large-magnitude volcanic eruption in 1831 CE. This event was estimated to have injected ~13 Tg of sulfur (S) into the stratosphere which produced various atmospheric optical phenomena and led to Northern Hemisphere climate cooling of ~1 °C. The source of this volcanic event remains enigmatic, though one hypothesis has linked it to a modest phreatomagmatic eruption of Ferdinandea in the Strait of Sicily, which may have emitted additional S through magma–crust interactions with evaporite rocks. Here, we undertake a high-resolution multiproxy geochemical analysis of ice-core archives spanning the 1831 CE volcanic event. S isotopes confirm a major Northern Hemisphere stratospheric eruption but, importantly, rule out significant contributions from external evaporite S. In multiple ice cores, we identify cryptotephra layers of low K andesite-dacite glass shards occurring in summer 1831 CE and immediately prior to the stratospheric S fallout. This tephra matches the chemistry of the youngest Plinian eruption of Zavaritskii, a remote nested caldera on Simushir Island (Kurils). Radiocarbon ages confirm a recent (<300 y) eruption of Zavaritskii, and erupted volume estimates are consistent with a magnitude 5 to 6 event. The reconstructed radiative forcing of Zavaritskii (−2 ± 1 W m −2 ) is comparable to the 1991 CE Pinatubo eruption and can readily account for the climate cooling in 1831–1833 CE. These data provide compelling evidence that Zavaritskii was the source of the 1831 CE mystery eruption and solve a confounding case of multiple closely spaced observed and unobserved volcanic eruptions.

A detailed spatiotemporal atlas of the white matter tracts for the fetal brain

This study presents the construction of a comprehensive spatiotemporal atlas of white matter tracts in the fetal brain for every gestational week between 23 and 36 wk using diffusion MRI (dMRI). Our research leverages data collected from fetal MRI scans, capturing the dynamic changes in the brain’s architecture and microstructure during this critical period. The atlas includes 60 distinct white matter tracts, including commissural, projection, and association fibers. We employed advanced fetal dMRI processing techniques and tractography to map and characterize the developmental trajectories of these tracts. Our findings reveal that the development of these tracts is characterized by complex patterns of fractional anisotropy (FA) and mean diffusivity (MD), coinciding with the intensity of histogenic processes such as axonal growth, involution of the radial-glial scaffolding, and synaptic pruning. This atlas can serve as a useful resource for neuroscience research and clinical practice, improving our understanding of the fetal brain and potentially aiding in the early diagnosis of neurodevelopmental disorders. By detailing the normal progression of white matter tract development, the atlas can be used as a benchmark for identifying deviations that may indicate neurological anomalies or predispositions to disorders.

Integrin-activating <i>Yersinia</i> protein Invasin sustains long-term expansion of primary epithelial cells as 2D organoid sheets

Matrigel ® /BME ® , a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells [T. Sato et al. , Nature 459 , 262–265 (2009); T. Sato et al. , Gastroenterology 141 , 1762–1772 (2011)]. Here, we show that interaction between Matrigel’s major component laminin-111 with epithelial α6β1-integrin is crucial for this process. The outer membrane protein Invasin of Yersinia is known to activate multiple integrin–β1 complexes, including integrin α6β1. A C-terminal integrin-binding fragment of Invasin, coated on culture plates, mediated gut epithelial cell adhesion. Addition of organoid growth factors allowed multipassage expansion in 2D. Polarization, junction formation, and generation of enterocytes, goblet cells, Paneth cells, and enteroendocrine cells were stable over time. Sustained expansion of other human, mouse, and even snake epithelia was accomplished under comparable conditions. The 2D “organoid sheet” format holds advantages over the 3D “in gel” format in terms of imaging, accessibility of basal and apical domains, and automation for high-throughput screening. Invasin represents a fully defined, affordable, versatile, and animal-free complement to Matrigel ® /BME ® .

Moisture-driven carbonation kinetics for ultrafast CO ₂ mineralization

CO 2 mineralization, a process where CO 2 reacts with minerals to form stable carbonates, presents a sustainable approach for CO 2 sequestration and mitigation of global warming. While the crucial role of water in regulating CO 2 mineralization efficiency is widely acknowledged, a comprehensive understanding of the underlying mechanisms remains elusive. This study employs a combined experimental and atomistic simulation approach to elucidate the intricate mechanisms governing moisture-driven carbonation kinetics of calcium-bearing minerals. A self-designed carbonation reactor equipped with an ultrasonic atomizer is used to meticulously control the water content during carbonation experiments. Grand Canonical Monte Carlo simulations reveal that maximum CO 2 uptake occurs at a critical water content where the initiation of capillary condensation significantly enhanced liquid–gas interactions. This phenomenon leads to CO 2 adsorption–driven ultrafast carbonation at an optimal moisture content (0.1 to 0.2 g/g, water mass ratio to total wet mass of the mineral). A higher moisture content decimates the carbonation rate by crippling CO 2 intake within mineral pores. However, at exceptionally high moisture levels, the carbonation reaction sites shift from internal mesopores to the grain surface. This results in surface dissolution–driven ultrafast carbonation, attributed to the monotonically decreasing free energy of dissolution with increasing surface water thickness, as revealed by metadynamics simulations. This study provides a fundamental and unified understanding of the multifaceted role of water in mineral carbonation, paving the way for optimizing ultrafast CO 2 mineralization strategies for global decarbonization efforts.