Browse Articles

Bacterial growth in poly(vinyl alcohol) hydrogel with nutrients and indicator

Biallelic variants in CELSR1 cause brain malformations, neurodevelopmental disorders and epilepsy in humans

Efficient adaptive rotated object detection for 1D and QR barcodes

Reconstructing the early spatial spread of pandemic respiratory viruses in the United States

Understanding the geographic spread of emerging respiratory viruses is critical for pandemic preparedness, yet the early spatiotemporal dynamics of the 2009 H1N1 pandemic influenza and severe acute respiratory syndrome coronavirus 2 in the United States remain unclear. While mobility and genomic data have revealed important aspects of pandemic spatial spread, several key questions remain: Did the two pandemics follow similar spatial transmission routes? How rapidly did they spread across the United States? What role did stochastic processes play in early spatial transmission? To address these questions, we integrated high-resolution disease data with a robust, data-efficient inference framework combining air travel, commuting flows, and pathogen superspreading potentials to reconstruct their spatial spread across US metropolitan areas. The two pandemics exhibited distinct transmission pathways across locations; however, both pandemics established local circulation in most metropolitan areas within weeks, driven by several shared transmission hubs. Early spatial spread was more strongly associated with air travel than with commuting, though stochastic dynamics introduced substantial uncertainty in transmission routes, creating challenges for timely detection and control. Simulations indicate that broad wastewater surveillance coverage beyond top transmission hubs coupled with effective infection control may slow initial spatial expansion. Our findings highlight the rapid, stochastic spread of pandemic respiratory pathogens and the difficulties of early outbreak containment.

Interphase electron redistribution induced by confined transformation in PtPdBiSn nanoplates for efficient ethanol oxidation electrocatalysis

Cuproptosis of bronchial epithelial cells triggers airway remodeling in chronic asthma

Prior novelty invigorates future mesolimbic target detection

The ability to adapt to a dynamic world relies on detecting, learning, and responding to environmental changes. The detection of novelty serves as a critical indicator of such changes, priming mechanisms to detect and respond to goal-relevant information. However, neural regions that support novelty detection (hippocampus) and goal-directed behavior [dopaminergic midbrain (VTA) and prefrontal cortex (PFC)] have yet to be described as a sequential process that unfolds over time. Using a forward-prediction functional MRI model, we explored interactions between the hippocampus, VTA, and PFC in humans performing a novelty-imbued target-detection task. Hippocampal novelty activation predicted subsequent VTA target activation, enhancing readiness to detect goal-relevant information. Concurrently, goal-directed PFC activation modulated VTA target activation, refining focus on behaviorally significant cues. These circuits function both synergistically and independently, promoting subsequent hippocampal activity during target trials. This work provides insights into how distributed circuits coordinate to optimize adaptive behavior.

Precise excision of expanded GGC repeats in NOTCH2NLC via CRISPR/Cas9 for treating neuronal intranuclear inclusion disease

Abstract Neuronal intranuclear inclusion disease (NIID) is an adult-onset neurodegenerative disease caused by expanded GGC repeats in the 5’ untranslated region of the human-specific NOTCH2NLC gene. The high sequence similarity between NOTCH2NLC and its paralogs poses a significant challenge for precise gene editing. Here, we develop a CRISPR/spCas9-based gene-editing strategy that precisely excises the expanded GGC repeats in NOTCH2NLC without detectable off-target effects on the highly homologous NOTCH2/NOTCH2NL family genes (<2% sequence divergence at this locus). The efficacy, specificity and safety of this approach are rigorously validated across multiple experimental models, including human cell lines, NIID iPSCs, and our previously established transgenic NIID mouse model. Our results demonstrate that precise excision of the expanded GGC repeats effectively alleviates NIID-related neuropathological, molecular and behavioral abnormalities. This study establishes the proof of concept for genome editing as a therapeutic strategy for NIID and other related repeat expansion disorders.

Prevalence and clinical significance of guideline-directed medical therapy in acute heart failure with reduced or mildly reduced ejection fraction

Constitutively high levels of endogenous soluble ST2 inhibit food allergic responses in mice

IL-33-induced signals via membrane-bound ST2 (ST2L) are critical for allergies. However, the physiological role of endogenous soluble ST2 (sST2) remains elusive. Here, we generated sST2-deficient mice with intact ST2L using the CRISPR/Cas9 system. Skin fibroblasts constitutively released sST2 protein at extremely high levels compared to mast cells, which did not reflect the expression levels of sST2 mRNA. This discrepancy can be partly explained by the sST2 protein degradation mediated by mast cell proteases. Accordingly, sST2 deficiency did not affect IL-33- and/or IgE plus antigen-stimulated mast cell activation in vitro. We provided evidence that constitutively high levels of sST2 suppress food allergies in mice by inhibiting IL-33-dependent, both expansion of jejunum mast cells and enhancement of their degranulation. Analysis of bone marrow chimeric mice under steady-state conditions showed that circulating sST2 was derived almost equally from hematopoietic and nonhematopoietic cells. Increased circulating sST2 in food-allergic mice was possibly and partly derived from fibroblasts stimulated by locally released IL-4 and IL-13. In conclusion, endogenous sST2 contributes to the suppression of food allergies.

Evolutionary dynamics of sex determination in Branchiostoma belcheri driven by repeated transposition of a single novel gene

Comparative analysis and verification on broken rock zone of model test based on multiple testing methods

Elevator mechanism dynamics in a sodium-coupled dicarboxylate transporter

VcINDY, the sodium-dependent dicarboxylate transporter from Vibrio cholerae , is responsible for C 4 -carboxylate uptake into cells. The molecular mechanism of how VcINDY physically moves substrates across the membrane, and does so in an energetically efficient manner, is unclear. Here, we use single-molecule fluorescence resonance energy transfer experiments to directly observe the individual mechanistic steps that VcINDY takes to translocate substrates across a lipid bilayer, and then test key predictions of transport cycle mechanistic models. Our data provide the first direct, dynamic evidence that VcINDY undergoes stochastic, elevator-type conformational motions that enable substrate translocation. The dynamics of these elevator motions are approximately an order of magnitude faster than the turnover rate for substrate transport, demonstrating that VcINDY undergoes multiple rounds of substrate translocation before a productive transport cycle is completed. Furthermore, the two protomers of the VcINDY homodimer undergo the substrate translocation motions in a noncooperative manner, and thus likely engage in independent transport reactions. The relative substrate independence of those motions supports the notion that the VcINDY transport cycle maintains strict cosubstrate coupling by a mechanism other than translocation inhibition. Thermodynamic modeling provides insight into how a cooperative binding mechanism is one such generalized approach to optimizing transport for many secondary active transporters.

Neural phase microscopy with metasurface optics for real-time and nanoscale quantitative phase imaging

An innovative chitosan-coated aquatic feed pellets production from coastal waste using top-spray fluidized bed drying

Hypersensitivity of chitin degradation to initial species densities due to monomer diffusion

Resource competition strongly shapes microbial community dynamics and functionality. In polysaccharide-degrading communities, primary degraders release hydrolytic enzymes, whereas exploiters consume released products without producing enzyme themselves. We investigate the competitive strategies employed by marine chitin degraders and N-acetylglucosamine (GlcNAc) exploiters, revealing various mechanisms that impact community viability and growth dynamics. In addition to direct competition strategies such as antibiotic secretion or cell aggregation on chitin particles (which helps monopolize enzyme access), exploiters also inhibit degraders by diverting limiting GlcNAc flux during the early stages of particle degradation. This critical phase requires degraders to overcome the diffusive loss of GlcNAc to sustain their chitinase production. Through quantitative measurements and modeling, we demonstrate that nutrient competition among species and nutrient loss through diffusion during the initial stages of community dynamics strongly influence the long-term success of the community. The initial community composition dictates the former mechanisms, while the latter is closely related to particle size, both of which have profound implications for environmental carbon cycling. The resulting hypersensitivity of the community is analogous to the Allee effect observed in population biology, where the outcomes—in our case polymer degradation—are heavily dependent on starting conditions. This study sheds light on how metabolic competition in the early phases of particle degradation governs species interactions, resource partitioning, and overall community viability, even under identical environmental and genetic conditions.

The biomedical landscape of genomic structural variation in the qatari population

A nationwide study of invasive Streptococcus agalactiae in the Faroe Islands from 2009 to 2024

Timing and magnitude of the Lomagundi–Jatuli carbon isotope excursion

The rise of atmospheric oxygen during the Great Oxidation Event (GOE) (ca. 2.5 to 2.1 billion years ago) permanently transformed Earth’s biogeochemical cycles. The chemistry of contemporaneous marine carbonates provides a window into operation of the carbon cycle across this transition. Specifically, carbonate rocks co-eval with the GOE preserve a large and long-lived positive carbon isotope ( δ 13 C) excursion, the Lomagundi–Jatuli excursion (LJE), that canonically is interpreted as an increase in organic matter burial linked to the oxygenation of Earth’s surface. However, the cause, synchroneity, and global nature of the LJE remain contentious due to significant uncertainties in the excursion’s timing and magnitude. These uncertainties stem from the incomplete, time-uncertain, and spatially variable nature of the shallow-water sedimentary record. Here, we use Bayesian inference to reconstruct Paleoproterozoic δ 13 C from globally distributed stratigraphic observations. Our inference reaffirms that the LJE is a global excursion, although its expression varies locally, and provides revised estimates for its timing and magnitude. We find that δ 13 C most likely began to increase at 2,445 Ma, subsequently returning to baseline values at 2,018 Ma. The most likely excursion peak occurs at 2,130 Ma, and it is very unlikely (5% probability) that peak δ 13 C values exceeded 9.1 ‰ . Altogether, our results indicate the LJE has an earlier onset, longer duration, and lower magnitude than previously thought. The initial δ 13 C increase occurs before or contemporaneously with both the earliest rise of atmospheric O 2 and Paleoproterozoic “snowball” glaciations, hinting at a mechanistic link among the LJE, the GOE, and climate.

Author Correction: Droplet surface spontaneous oxidation as a dominant formation pathway of organosulfates in the marine atmosphere