Browse Articles

Phosphorylation toggles the SARS-CoV-2 nucleocapsid protein between two membrane-associated condensate states

Abstract The Nucleocapsid protein (N) of SARS-CoV-2 plays a critical role in the viral lifecycle by regulating RNA replication and by packaging the viral genome. N and RNA phase separate to form condensates that may be important for these functions. Both functions occur at membrane surfaces, but how N toggles between these two membrane-associated functional states is unclear. Here, we reveal that phosphorylation switches how N condensates interact with membranes, in part by modulating condensate material properties. Our studies also show that phosphorylation alters N’s interaction with viral membrane proteins. We gain mechanistic insight through structural analysis and molecular simulations, which suggest phosphorylation induces a conformational change in N that softens condensate material properties. Together, our findings identify membrane association as a key feature of N condensates and provide mechanistic insights into the regulatory role of phosphorylation. Understanding this mechanism suggests potential therapeutic targets for COVID infection.

Correction: A comprehensive mapping of stress system interactions with pain and their contribution to chronification of musculoskeletal pain: Protocol of the STRAIN study

Scientific meetings debate the effect of climate change on future food production

Bringing the uncultivated microbial majority of freshwater ecosystems into culture

Abstract Axenic cultures are essential for studying microbial ecology, evolution, and genomics. Despite the importance of pure cultures, public culture collections are biased towards fast-growing copiotrophs, while many abundant aquatic prokaryotes remain uncultured due to uncharacterized growth requirements and oligotrophic lifestyles. Here, we applied high-throughput dilution-to-extinction cultivation using defined media that mimic natural conditions to samples from 14 Central European lakes, yielding 627 axenic strains. These cultures include 15 genera among the 30 most abundant freshwater bacteria identified via metagenomics, collectively representing up to 72% of genera detected in the original samples (average 40%) and are widespread in freshwater systems globally. Genome-sequenced strains are closely related to metagenome-assembled genomes (MAGs) from the same samples, many of which remain undescribed. We propose a classification of several novel families, genera, and species, including many slowly growing, genome-streamlined oligotrophs that are notoriously underrepresented in public repositories. Our large-scale initiative to cultivate the “uncultivated microbial majority” has yielded a valuable collection of abundant freshwater microbes, characterized by diverse metabolic pathways and lifestyles. This culture collection includes promising candidates for oligotrophic model organisms, suitable for a wide array of ecological studies aimed at advancing our ecological and functional understanding of dominant, yet previously uncultured, taxa.

Retraction: Combination of mTOR and EGFR kinase inhibitors blocks mTORC1 and mTORC2 kinase activity and suppresses the progression of Colorectal Carcinoma

Interferon-stimulated gene screening identifies CCND3 as a host restriction factor against emerging high-pathogenic bandaviruses

From static to dynamic: Embracing dynamics in isotopic diet estimation

Isotopic mixing models are widely used in ecology to quantify the diets of organisms. Most of these models assume that stable isotopic systems remain stable over time (a premise known as the steady-state hypothesis) and are therefore referred to as static mixing models. However, evidence shows that temporal dynamics—such as variations in isotopic turnover rates, diet shifts, and fluctuations in the isotopic signatures of both sources and consumers—can introduce significant bias into model outputs. Despite the recognition of such dynamics, the factors influencing bias and its implications remain underexplored. This study uses modelling and in silico experiments to characterize bias in mixing models resulting from temporal dynamics and to develop a dynamic mixing model that accounts for these effects. The results revealed that bias is strongly influenced by the interaction between the isotopic turnover rate and sampling frequency, emphasizing the importance of time variability in isotopic turnover. Additional sources of bias include the consumer’s isotopic signature prior to a dietary shift, which reflects the distance from equilibrium with the new diet. This bias can be further amplified by temporal fluctuations in source signatures. Our study also evaluates previously recommended strategies to mitigate bias, confirming their effectiveness in reducing errors in static models and providing additional guidelines for their application. Furthermore, it improves access to a dynamic mixing model, enabling direct comparison with static approaches and demonstrating its robustness and accuracy in estimating diets under dynamic conditions.

DeFrND: detergent-free reconstitution into native nanodiscs with designer membrane scaffold peptides

Exploring preparatory reading in bidirectional sight and written translation through clustering analysis of eye-tracking data

Preparatory reading—the phase between a translator’s initial reading of the source text and the production of the first word of the target text—remains underexplored despite its crucial role in both sight (SiT) and written translation (WT). This study examined preparatory reading patterns of 32 student translators, focusing on the effects of translation mode (SiT vs. WT) and direction (L1-to-L2 vs. L2-to-L1). Translators’ attention allocation, cognitive effort, and reading speed were measured using preparatory reading duration, average fixation duration, and fixation rate (i.e., number of fixations per second) as key indicators. Using linear mixed-effect models, we quantified the effects of translation mode and direction on each measure. We then synthesized all three measures by employing unsupervised machine learning algorithms (i.e. k-means cluster analysis) to identify distinct reading patterns. These quantitative findings were further complemented by expert qualitative categorization of reading patterns, achieved through subjective coding of scanpaths and Translation Process Graphs. We found that translation mode played a primary role in shaping preparatory reading styles, with SiT consistently requiring greater cognitive effort, more attention, and slower reading speeds than WT—particularly under the L1-to-L2 condition. Translation direction further modulated these effects in nuanced ways. Specifically, L2-to-L1 was associated with increased attention allocation in WT, but with less cognitive effort and faster reading in SiT. Additionally, we found three distinct preparatory reading patterns: Fast Surface-level Preparatory Reading, Systematic Deep-level Preparatory Reading, and Extended Iterative Preparatory Reading, each reflecting a distinct combination of cognitive investment and reading speed. These findings could advance our understanding of translators’ preparatory reading behaviors and underscore the need to equip them with adaptable, task-sensitive reading strategies that align with the cognitive demands of different translation modes and directions.

Simultaneous in vitro expression of minimal 21 transfer RNAs by tRNA array method

Is there a difference in thresholds for revision between shoulder arthroplasty types? A National Joint Registry Study

Introduction Shoulder arthroplasty procedures have increased significantly, with reverse shoulder arthroplasty (RSA) becoming more common. While RSA revision rates are reported as low, these figures may not accurately reflect implant success. Factors such as older patient demographics and surgeon reluctance to perform complex revisions may contribute to lower revision rates. This perception may encourage broader RSA use in younger patients, potentially increasing long-term revision burdens. This study examines whether revision thresholds differ between shoulder arthroplasty types to determine if low revision rates reported signify true implant success. Methods All shoulder arthroplasties from the 1st April 2012 to the 31st March 2022 were requested from the National Joint Registry (NJR). Mean postoperative Oxford Shoulder Score (OSS) was calculated for RSA, total shoulder arthroplasty (TSA), and hemiarthroplasty (HA). Revision rates were analysed between implants for patients with a mean postoperative OSS of <29 (a pre-defined unsatisfactory score) and those with the lowest 25%, and lowest 10% of OSS scores. Chi-squared tests with Bonferroni correction assessed differences among implant groups. Results Among 21,918 NJR patients with postoperative OSS data, HA had the highest proportion of patients with ‘unsatisfactory’ function (38.12%), followed by RSA (26.99%) and TSA (15.35%). 4.87% of RSA patients with unsatisfactory function were revised, significantly less than TSA (10.58%) and HA (13.86%) (p < 0.001). In those with the lowest 25% of OSS scores, revision rates were 4.78% for RSA, 8.76% for TSA, and 15.02% for HA (p < 0.001). In the lowest 10%, revisions occurred in 6.53% of RSAs, 12.44% of TSAs, and 17.03% of HAs (p < 0.001). No significant difference was found between TSA and HA (p = 0.06). Conclusion RSA has lower revision rates than HA and TSA; however, this may not reflect superior implant performance. Patients with poor RSA function are less likely to undergo revision, suggesting higher revision thresholds. As RSA use expands, its assumed low revision rate must be reassessed to prevent long-term burdens of poorly functioning implants. Further research is needed to determine whether surgical selection bias influences revision rates and to establish additional benchmarks or surrogates in joint registries for a more comprehensive assessment of implant performance.

scIVNL-seq resolves in vivo single-cell RNA dynamics of immune cells during Salmonella infection

A comparative study of the changes in the quality of life among patients with homonymous hemianopia, monocular blindness, or binocular diplopia

To investigate changes in health-related quality of life (HRQOL), patients with homonymous hemianopia due to unilateral brain damage, monocular blindness with a best-corrected visual acuity of 20/1000 or less, or binocular diplopia for at least 6 months were enrolled. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was used to evaluate the changes in HRQOL before and after the onset of the causative disease within and between the three study groups. The patients were asked to recall their state before disease onset and record it as accurately as possible for each question of the NEI VFQ-25, as well as score their current status. Among 43 included patients, 20 had homonymous hemianopia, 13 had monocular blindness, and 10 had binocular diplopia. The mean patient age was 56 years, and 12 patients were women (28%). A significant decrease in all HRQOL subscale scores was observed in the homonymous hemianopia and monocular blindness groups. In the binocular diplopia group, a lower number of subscales showed decreases in HRQOL. However, the changes in HRQOL before and after disease onset did not differ between groups. In conclusion, HRQOL change before and after homonymous hemianopia and monocular blindness did not differ. Considering the development background of the NEI VFQ-25, this questionnaire may not be sufficiently sensitive to distinguish HRQOL changes between the two disease groups. Hence, the NEI VFQ-25 might be useful for comparing HRQOL changes before and after the onset of a specific disease or before and after treatment, while not being sensitive to differentiate HRQOL differences between diseases. Thus, caution is needed when using the NEI VFQ-25 to compare HRQOL differences between disease groups.

Defining the cell and molecular origins of the primate ovarian reserve

Abstract The primate ovarian reserve is established during late fetal development and consists of quiescent primordial follicles in the ovarian cortex each composed of granulosa cells surrounding an oocyte in dictate. As late stages of fetal development are not routinely accessible using human tissues, the current study exploits the evolutionary proximity of the rhesus macaque to investigate follicle formation in primates. Like in humans, the rhesus prenatal ovary develops multiple types of pre-granulosa cells in time and space, with primordial follicles deriving from later emerging pre-granulosa subtypes. In addition, our work shows that activated medullary follicles recruit fetal theca cells to establish a two-cell system for sex-steroid hormone production prior to birth, providing a cell-based explanation for mini puberty.

Whole-Genome sequencing of Chikungunya Virus (CHIKV) from Pakistan: Detection of the East/Central/South African (ECSA) genotype during the 2024 outbreak in Mansehra

The 2024 chikungunya virus (CHIKV) outbreak in Mansehra, Khyber Pakhtunkhwa, Pakistan, marked a significant public health event, providing a unique opportunity to investigate the genomic diversity and evolutionary dynamics of circulating strains. Using metagenomic next-generation sequencing (mNGS), we analyzed serum samples from patients presenting with acute febrile illness and joint pain, identifying 16 CHIKV-positive cases, six of which yielded near-complete genomes. Phylogenetic analysis revealed that all isolates belonged to the East/Central/South African (ECSA) genotype, closely related to strains from India (2020–2024) and China (2017). Notably, this study represents the first comprehensive whole-genome sequencing of CHIKV in Pakistan, uncovering unique mutations in structural (E1: I28V, V290I; E2: Y39H, D54E) and non-structural proteins (NSP1: I167V, M376T; NSP4: G27R, P52S, I403V), suggesting potential viral adaptations to local environmental and vector conditions. The absence of the E1-A226V mutation, associated with enhanced transmission by Aedes albopictus, highlights the need for continued genomic surveillance to monitor emerging variants. Additionally, the detection of a GB virus-C co-infection in one case underscores the utility of mNGS in identifying co-circulating pathogens. This study provides critical insights into the genomic landscape of CHIKV in Pakistan, emphasizing the importance of enhanced surveillance, diagnostics, and vector control strategies to mitigate future outbreaks. The findings underscore the necessity of regional collaboration and genomic monitoring to address the evolving threat of CHIKV in South Asia.

Distinct manifestations of excitatory-inhibitory imbalance associated with amyloid-β and tau in patients with Alzheimer’s disease

Abstract A growing body of evidence shows that epileptic activity is frequently observed in patients with Alzheimer’s disease (AD), implicating underlying excitatory-inhibitory imbalance. The distinction of whether the AD-epileptic phenotype represents a subset of patients or an underdiagnosed manifestation holds major therapeutic implications. Here, we quantified the excitatory-inhibitory imbalance in AD patients using magnetoencephalography and examined the relationships to AD pathophysiology—amyloid-beta and tau, and to epileptic activity. We used two metrics to quantify regional excitatory-inhibitory imbalance distinguishing between local hyperexcitability (Neural excitability, quantified by regional aperiodic spectral slope) and aberrant long-range synaptic input integration (Neural fragility, quantified by regional linear dynamic instability). We found that amyloid-beta correlated with higher neural fragility and higher neural excitability, while tau and hypometabolism uniquely correlated with higher neural excitability. Importantly, the AD-epileptic phenotype showed a distinctive increase in neural fragility. Our findings demonstrate that AD pathophysiology is associated with diverse mechanisms of excitatory-inhibitory imbalance and that AD-epileptic phenotype represents a distinct group of patients with greater impairments in long-range synaptic input integration.

Correction: Impact of immune evasion, waning and boosting on dynamics of population mixing between a vaccinated majority and unvaccinated minority

Programmable epigenome editing by transient delivery of CRISPR epigenome editor ribonucleoproteins

Abstract Programmable epigenome editors modify gene expression in mammalian cells by altering the local chromatin environment at target loci without inducing DNA breaks. However, the large size of CRISPR-based epigenome editors poses a challenge to their broad use in biomedical research and as future therapies. Here, we present Robust ENveloped Delivery of Epigenome-editor Ribonucleoproteins (RENDER) for transiently delivering programmable epigenetic repressors (CRISPRi, DNMT3A-3L-dCas9, CRISPRoff) and activator (TET1-dCas9) as ribonucleoprotein complexes into human cells to modulate gene expression. After rational engineering, we show that RENDER induces durable epigenetic silencing of endogenous genes across various human cell types, including primary T cells. Additionally, we apply RENDER to epigenetically repress endogenous genes in human stem cell-derived neurons, including the reduction of the neurodegenerative disease associated V337M-mutated Tau protein. Together, our RENDER platform advances the delivery of CRISPR-based epigenome editors into human cells, broadening the use of epigenome editing in fundamental research and therapeutic applications.

Assessment of the stopping for right-turning large vehicles policy in Nanjing: Effectiveness and determinants

This study evaluates the effectiveness of Stopping for Right-Turning Large Vehicles Policy in Nanjing, designed to mitigate accidents attributed to blind spots and delayed braking of large trucks at intersections. Using high-resolution conflict data from four signalized intersections in Jiangning District, collected via unmanned aerial vehicles (UAVs) and roadside video, the research employs K-means clustering for conflict severity classification and binomial Logit regression to identify critical determinants. Results reveal the policy exhibited limited statistical significance in reducing severe conflicts (p > 0.05). Regression analysis quantified four critical determinants: absence of motorized/non-motorized segregation (OR=1.82, + 81.6% severity odds), elevated stop-line speeds (OR=1.32, + 31.9%), failure to yield (OR=2.45, + 145%), and crossing the street within the zebra crossing (OR=0.19, −81.0%). The analysis demonstrates that infrastructural deficiencies and behavioral non-compliance outweigh the policy’s standalone impact. Based on these findings, the study proposes a holistic optimization framework integrating physical separation measures, enhanced signage, dynamic traffic signal adjustments, and data-driven enforcement strategies. Methodologically, this study innovatively combines unsupervised learning for conflict categorization, providing a scalable framework for evaluating urban traffic policies. This research underscores the necessity of multi-dimensional interventions—spanning infrastructure, enforcement, and public education—to achieve sustainable improvements in intersection safety. The findings offer actionable insights for policymakers to refine regulatory measures and enhance road safety in rapidly urbanizing environments.

Strong crystalline thermal insulation induced by extended antibonding states