Browse Articles

Ebola virus VP35 NNLNS motif modulates viral RNA synthesis and MIB2-mediated signaling

Ebola virus (EBOV) is a nonsegmented, negative-sense virus (NNSV) with a single-stranded RNA genome. EBOV encodes for a limited number of proteins and thus depends on host factors to facilitate viral replication and pathogenesis. Of the virus-encoded proteins, multifunctional EBOV VP35 (eVP35) is necessary for host immune evasion and viral RNA synthesis. Previous proteomics studies identified an interaction between eVP35 and the host E3 ubiquitin ligase Mindbomb 2 (MIB2). Here, we show how an NNLNS (Asn-Asn-Leu-Asn-Ser) motif (residues 201 to 205) within eVP35 serves as a binding site for MIB2. This motif is critical for eVP35-dependent inhibition of MIB2-mediated interferon induction. It is also important for EBOV RNA synthesis as MIB2 binding to eVP35 inhibited EBOV minigenome activity. Altogether, these findings highlight the importance of the eVP35 protein and the role of host factors in EBOV infection.

Multi scale self supervised learning for deep knowledge transfer in diabetic retinopathy grading

Abstract Diabetic retinopathy is a leading cause of vision loss, necessitating early, accurate detection. Automated deep learning models show promise but struggle with the complexity of retinal images and limited labeled data. Due to domain differences, traditional transfer learning from datasets like ImageNet often fails in medical imaging. Self-supervised learning (SSL) offers a solution by enabling models to learn directly from medical data, but its success depends on the backbone architecture. Convolutional Neural Networks (CNNs) focus on local features, which can be limiting. To address this, we propose the Multi-scale Self-Supervised Learning (MsSSL) model, combining Vision Transformers (ViTs) for global context and CNNs with a Feature Pyramid Network (FPN) for multi-scale feature extraction. These features are refined through a Deep Learner module, improving spatial resolution and capturing high-level and fine-grained information. The MsSSL model significantly enhances DR grading, outperforming traditional methods, and underscores the value of domain-specific pretraining and advanced model integration in medical imaging.

Childhood allostatic load predicts cardiometabolic health in adulthood

Allostatic load (AL) measures multisystem physiological functioning to reflect the cumulative burden of chronic stress. Incurring AL during sensitive developmental periods such as childhood may affect health outcomes later in life, but longitudinal measures to test these life course effects are lacking. This study tested associations between childhood AL and adult cardiometabolic health in a large sample of youth repeatedly measured across ages 9 to 16, and their adult cardiometabolic health at age 30. AL scores were calculated at each age by summing across sex- and age-standardized values for biomarkers representing immune (C-Reactive Protein, Epstein–Barr Virus antibodies), neuroendocrine (cortisol, DHEA-s), and cardiometabolic indicators (body mass index; BMI). Adult cardiometabolic health was measured using a composite sum score of sex-standardized systolic and diastolic blood pressure, BMI, and waist-to-hip ratio. Multiple approaches aggregating repeated AL scores were tested, including mean, maximum, oldest available AL score across childhood, and a version omitting BMI from the index. Childhood AL was significantly associated with adult cardiometabolic health ( P < 0.001), with higher AL predicting worse cardiometabolic outcomes at age 30 in all models, regardless of how AL was defined. Sensitivity analyses to address potential bias from missing observations using 20 imputed datasets were consistent with unimputed models. Follow-up analyses suggested risk for adult cardiometabolic outcomes was primarily associated with C-reactive protein, DHEA-s, and childhood BMI. In this cohort study, physiological dysregulation experienced in early life had lasting consequences. These results underscore the importance of childhood as a sensitive period during which cumulative stress exposure can shape long-term health trajectories.

Species habitat modeling based on image semantic segmentation

In vitro maturation of fully active [FeFe]-hydrogenase in a defined system including the iron carrier NfuA

The [FeFe]-hydrogenase employs an active-site 6Fe H-cluster to catalyze the reversible reduction of protons to H 2 . A [4Fe-4S] subcluster of the H-cluster is synthesized by housekeeping iron-sulfur cluster assembly machinery, and then dedicated hydrogenase maturation enzymes, together with components of the glycine cleavage system, build and deliver a [2Fe] subcluster to generate the full H-cluster. Here, we report that the Escherichia coli iron-sulfur carrier protein NfuA supports in vitro maturation of fully active [FeFe]-hydrogenase, with H 2 production rates comparable to that of the in vivo - matured Chlamydomonas reinhardtii [FeFe]-hydrogenase ( Cr HydA). Inclusion of NfuA in the in vitro maturation process improves its efficacy by delivering the iron essential for formation of the [Fe II (cys)(CN)(CO) 2 ] – synthon at the dangler iron site of the HydG auxiliary cluster. NfuA serves an additional role in reconstituting and maintaining the catalytically essential iron-sulfur clusters on the maturase enzymes HydE, HydF, and HydG. Further inclusion of a high CO affinity myoglobin variant (Mb H64L ) sequesters free CO generated during the maturation process, minimizing formation of the CO-inhibited H ox -CO enzyme state, significantly increasing hydrogenase activity. The addition of NfuA and Mb H64L to the fully defined maturation system thus results in an in vitro [FeFe]-hydrogenase maturation system that generates highly active enzyme while providing insights into factors important to in vivo maturation.

Scrutinizing the inherent half-metallicity, electronic structure, mechanical stability, optical and thermoelectric response of d-electron based Sc2VX (X = Si, Ge) Heusler alloys

Emergence of activation or repression in transcriptional control under a fixed molecular context

Transcription factors (TFs) can be both activators and repressors of gene transcription. This can manifest as “duality,” where the transcriptional response increases (activation) with TF concentration in one context but decreases (repression) in another context, or as “nonmonotonicity,” where, in the same context, the response increases in part of the concentration range and decreases outside that range. Here we use biophysical models of gene regulation to investigate how duality and nonmonotonicity relate to the interactions between a TF, Polymerase and the regulatory DNA. We distinguish two modes of TF action on Polymerase: “coherent,” with interactions either positive or negative, and “incoherent,” where interactions are a mix of both. For TFs that act incoherently from a single TF–DNA binding site, nonmonotonicity can arise, but only under nonequilibrium models. For single-site models, we show that nonmonotonicity can never happen under the common thermodynamic models of gene regulation, which consider equilibrium conditions and ignore the dissipative nature of the transcription process. Moreover, we show that merely changing the TF–DNA binding affinity, while keeping other features fixed, can tune the response between activation and repression, with responses either evaluated as a function of TF concentration or site number. Using the mammalian Sp1 as a case study and synthetically designed target sequences, we find experimental evidence for nonmonotonicity, and activation or repression tuned by affinity, which we interpret as evidence of incoherent action. Our work highlights the importance of moving from a TF-centric view to a systems view when reasoning about transcriptional control.

Unveiling the antifungal and antibiofilm potential of green synthesized silver nanoparticles from leaf extract of Selaginella bryopteris

Abstract The emergence of highly drug-resistant fungal strains is the major concern in health care sector. There is an urgent need to develop novel and potent antifungal drugs with minimal side effects to encounter invasive fungal infections. In this study, we have green-synthesized silver nanoparticles (AgNPs) by using leaf extract of Selaginella bryopteris and checked their antifungal activity against different Candida spp. The optimization of parameters involved in the synthesis of AgNPs includes pH, temperature, concentration of silver nitrate, reaction time. The synthesis of NPs was investigated by the UV–Vis spectrophotometric analysis. The physicochemical properties of AgNPs were further analysed by FESEM, TEM, DLS, zeta potential, FTIR and XRD studies. AgNPs were found to be spherical in shape with an average size of 35 nm and were monodispersed in nature without any agglomeration. The results of antifungal susceptibility testing (AFST) and growth curve kinetics revealed that AgNPs displayed significant anticandidal activity with MIC and MFC values of 0.003 and 0.006 ng/mL respectively. Treatment of Candida spp. with AgNPs leads to damage in fungal cell wall, cell membrane along with disruption of mitochondrial enzyme activity and release of nuclear content. The green-synthesized AgNPs not only caused damage and destruction to the morphology of Candida but also affected the ergosterol biosynthetic pathway. The green-synthesized AgNPs were also found to exhibit antibiofilm activity against Candida spp. which was assessed by crystal violet assay and SEM analysis confirming biofilm reduction by 80–82% as compared to control.

Châtelperronian cultural diversity at its western limits: Shell beads and pigments from La Roche-à-Pierrot, Saint-Césaire

The timing and mechanisms underlying the gradual replacement of Neanderthal populations by Homo sapiens groups have elicited heated debate for decades. The Châtelperronian of France and northern Spain has figured prominently in these discussions. While the Neanderthal authorship of this techno-complex is far less certain than previously thought, the Châtelperronian is now generally accepted as being among the first genuine Upper Paleolithic industries in Eurasia rather than a “transitional” stone tool technology. Here, we report the first association of shell beads with Châtelperronian artifacts from new excavations at the site of La-Roche-à-Pierrot, Saint-Césaire (France), supported by a multiproxy spatial analysis that incorporates site formation processes. Similar types of personal ornaments are unknown from Middle Paleolithic contexts. Comparable examples have, however, been recovered from contexts penecontemporaneous with the Châtelperronian in south-eastern Europe and around the Mediterranean. This hitherto undocumented combination of an early Upper Paleolithic industry and shell beads provides insights into cultural variability in western Europe and raises the question as to whether the makers of the Châtelperronian were influenced by or formed part of the earliest dispersals of H. sapiens into the region.

Design, synthesis, and antimicrobial evaluation of novel quinazoline piperazine phosphorodiamidate hybrids as potent DNA gyrase inhibitors

Abstract Antimicrobial resistance poses a critical challenge to global public health, exacerbating morbidity and mortality associated with bacterial infections. This study addresses the urgent need for novel antibacterial agents by exploring the design and synthesis of quinazoline-piperazine phosphorodiamidate hybrids (6a-g) as potential DNA gyrase inhibitors. Antibacterial activity was evaluated using the agar well diffusion method, revealing significant inhibition zones for compounds 6f, 6 g, 6a, and 6c compared to the standard drug Amoxyclav. Minimum inhibitory concentration (MIC) measurements further supported the potent antibacterial effects of these compounds. Additionally, compounds 6f, 6 g, and 6a exhibited notable antifungal activity superior to Fluconazole. Molecular docking simulations against DNA gyrase demonstrated strong binding affinities of compounds 6f and 6a with dock scores surpassing that of a standard antibiotic, ciprofloxacin. Detailed analysis of binding interactions highlighted key residues involved in stabilizing the ligand-protein complexes, providing insights into their mechanism of action. Furthermore, in silico ADMET prediction studies revealed that the targeted analogs satisfied the drug like characteristics of CNS acting drugs against antimicrobial diseases.

Dried fish provide widespread access to critical nutrients across Africa

Aquatic foods are essential in supporting food security and nutrition across the tropics, with “dried” fish particularly affordable, available, and nutritious. However, dried fish food systems are often hidden and overlooked due to data scarcity, limiting understanding of how dried fish contribute to nutrient intakes. Here, we combine nutrient analysis of fish samples with national household surveys from across East and West Africa to understand the importance of dried fish in diets. We find that small portions of dried fish contribute over 15% of recommended intakes for multiple essential dietary nutrients (calcium, iodine, iron, selenium, zinc, and vitamins B12 and D), with low heavy metal concentrations, and are consumed weekly by ~one-third of households in six countries (Côte d’Ivoire, Nigeria, Malawi, Senegal, Tanzania, and Uganda) (~144 million people). Dried fish consumption was more prevalent than fresh fish, reaching 54% more people, particularly those in poor households and near to marine coastlines or urban centers. The widespread prevalence of nutritious dried fish suggests that these foods and their distribution networks play critical roles in food security and nutrition, even in households distant from fisheries or urban centers. Dried fish can fill nutrient gaps across the tropics but will require policies that mitigate negative effects of overfishing, environmental changes, and competition with international markets, while providing postharvest support to fish processors.

Evaluating general practitioners’ knowledge and attitude of autism spectrum disorder and influencing factors at Gondar University Hospital, Gondar, Ethiopia

Coding of tool use independent of body part

Comparative analysis of cysteine protease nano-formulations to manage callosobruchus maculatus fabricius and trogoderma granarium everts in stored products

Exploring exoplanet dynamics with JWST: Tides, rotation, rings, and moons

Although nearly 6,000 exoplanets are currently known, in most cases, our knowledge is limited to a handful of the planet’s orbital characteristics and bulk properties such as radius and mass. The James Webb Space Telescope (JWST) can expand our knowledge not only by probing exoplanet atmospheres but also by measuring additional orbital and physical properties of exoplanets, thanks to its superior light-gathering power and measurement precision. Here, we describe the potential of JWST to unveil dynamical phenomena that were previously beyond our reach, such as tidal distortion and inflation, rotational flattening, planetary rings, and moons.

A car-following model of CAVs integrating state information from multiple leading and single following vehicles

Prospects for detecting signs of life on exoplanets in the JWST era

The search for signs of life in the Universe has entered a new phase with the advent of the James Webb Space Telescope (JWST). Detecting biosignature gases via exoplanet atmosphere transmission spectroscopy is in principle within JWST’s reach. We reflect on JWST’s early results in the context of the potential search for biological activity on exoplanets. The results confront us with a complex reality. Established inverse methods to interpret observed spectra—already known to be highly averaged representations of intricate three dimensional (3D) atmospheric processes—can lead to disparate interpretations even with JWST’s quality of data. Characterizing rocky or sub-Neptune-size exoplanets with JWST is an intricate task, and moves us away from the notion of finding a definitive “silver bullet” biosignature gas. Indeed, JWST results necessitate us to allow “parallel interpretations” that will perhaps not be resolved until the next generation of observatories. Nonetheless, with a handful of habitable-zone planet atmospheres accessible given the anticipated noise floor, JWST may continue to contribute to this journey by designating a planet as biosignature gas candidate. To do this we will need to sufficiently refine our inverse methods and physical models for confidently quantifying specific gas abundances and constraining the atmosphere context. Looking ahead, future telescopes and innovative observational strategies will be essential for the reliable detection of biosignature gases.

Construction and evaluation of a prognostic model for breast cancer based on aging related genes

Exploring the sub-Neptune frontier with JWST

Sub-Neptune planets, with sizes and masses between those of Earth and Neptune, dominate the exoplanet population. Sub-Neptunes are expected to be the most diverse family of the exoplanet population, potentially including rocky gas dwarfs, water worlds, and mini-Neptunes, with a wide range of atmospheric, surface, and interior conditions. With no analogue in the solar system, these planets open fundamental questions in planetary processes, origins, and habitability, and present avenues in the search for life elsewhere. Atmospheric observations with the James Webb Space Telescope (JWST) are enabling unprecedented characterization of sub-Neptunes, starting with the first detections of carbon-bearing molecules in the habitable zone sub-Neptune K2-18 b. We survey the present landscape of JWST observations and atmospheric inferences of sub-Neptunes, which in turn provide key insights into their atmospheric processes, internal structures, surface conditions, formation pathways, and potential habitability. The atmospheric abundance constraints reveal evidence of chemical disequilibria, and insights into the planetary mass–metallicity relation in the sub-Neptune regime. Similarly, for sub-Neptunes with H 2 O-rich interiors, increasing atmospheric H 2 O abundances with the equilibrium temperature may indicate the existence of a critical temperature for transition from H 2 dominated atmospheres with tropospheric cold traps to those with steamy atmospheres. The chemical abundances also provide initial evidence for diverse planet types, from potentially habitable hycean worlds to steam worlds with supercritical water layers. These planet types serve as benchmarks for an emerging taxonomy of volatile-rich sub-Neptunes as a function of their equilibrium temperature and atmospheric extent, heralding a new era of chemical classification of low-mass exoplanets with JWST.

Proteomic analysis of brain and spinal cord tissue reveals distinct immune and mitochondrial processes between human and mouse ALS models

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease resulting in the progressive loss of motor neurons in the brain and spine. More than 95% of cases are pathologically characterized by the cytoplasmic accumulation of hyperphosphorylated and ubiquitinated transactive response DNA-binding protein 43 (TDP-43). Multiple mouse models with TDP-43 accumulation have been developed, however, whether they recapitulate molecular features of ALS pathology is unclear. Given the lack of curative treatment for ALS, there is an urgent need to identify the precise biological processes contributing to disease pathogenesis for the development of effective therapeutic treatments. Thus, in this study we employed label-based untargeted proteomics to characterize the ALS proteome and related biological processes in the spinal cord and brain of TDP-43Q331K mice, a transgenic mouse model of ALS and the motor cortex and the cervical, thoracic, and lumbar spinal cord regions from humans. In humans, we observed highly overlapping responses across the four tissues examined, primarily related to the upregulation of immune processes and the downregulation of mitochondrial function. In contrast, TDP-43Q331K mice demonstrate a lack of enrichment for immune activation and the opposite regulation of mitochondrial processes. A meta-analysis of previously published mouse datasets identified the Ubqln2 knock-out mouse model as showing stronger parallels with our late-stage human ALS. Overall, this study provides in-depth analysis of the site-specific dysregulated proteomes and their associated functional processes across species. Thereby, identifying potential therapeutic targets while emphasizing the limitations of specific mouse models at certain timepoints in recapitulating ALS-related processes for future model development.