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Development of a Bacterial Colorimetric Reporter System for Functional Screening of SARS-Cov-2 Main Protease Inhibitors Using Plant Preparations (juices): A Proof-of-Concept Study

SARS-CoV-2 main protease (Mpro) is essential for viral polyprotein processing and represents a prime target for antiviral drug discovery. However, most available screening strategies rely on biochemical and computational approaches that lack the biological context of living cells, or costly mammalian-cell based models. Therefore, there remains a shortage of simple and biosafe cellular models enabling rapid, functional screening of potential Mpro inhibitors, particularly those derived from nat...

— Issa, S. S., Zelinsky, A., Fayoud, H., Zhidkin, R., Matveeva, T. V. 2025-12-15 00:00:00

Chemoproteomic elucidation of β-lactam drug targets in Mycobacterium abscessus

The pathogen Mycobacterium abscessus (Mab) can cause severe and difficult to treat chronic lung infections. Despite the rising incidence and clinical concern of Mab infections, treatment options are limited and often ineffective. Treatment is complicated by Mabs ability to persist in a non-replicative, drug-resistant state. Several {beta}-lactam antibiotics are potently bactericidal against Mab but are underutilized because their molecular mechanisms of action against Mab are incompletely und...

— Devlin, K. L., Hutchinson, E., Leach, D. T., Nelson, W. C., Gorham, L. J., Lamichhane, G., Lin, V. S., Beatty, K. E. 2025-12-15 00:00:00

Engineered Proteins Mimic ssRNA Phage to Disrupt Type IV Pili

Antimicrobial resistance is a growing global health crisis, with ESKAPE pathogens, such as Acinetobacter species, contributing significantly to hospital-acquired infections. These bacteria employ various virulence factors, including extracellular type IV pili (T4P), which serve as essential appendages for DNA uptake, biofilm formation, and resistance to antibiotics. Single-stranded RNA (ssRNA) bacteriophages (phages) exploit these retractile pili as entry receptors, but the exact mechanism of...

— Frese, A., Zhao, Z., Zeng, L. 2025-12-15 00:00:00

The microbiome of Antarctica's endemic chironomid midge: from general microbial community to endosymbiotic bacteria

Background: The interactions between the host organism and the microbiota play an important role in the host's survival, influencing its physiology and adaptation. The Antarctic, due to its extreme living conditions, is a unique region for studying such interactions. However, research on the microbiomes of Antarctic terrestrial and freshwater invertebrates remains limited, especially with regard to the region's sole endemic insect, Belgica antarctica. Our aim was to study the B. antarctica mi...

— Kovalenko, P. A., Pavlovska, M. O., Prekrasna-Kviatkovska, Y. P., Puhovkin, A. Y., Kozeretska, I. A. 2025-12-15 00:00:00

Genomic rearrangement of the capsule operon in a phylogenetically distinct cluster of the multi-drug resistant Escherichia coli lineage ST131

Escherichia coli ST131 is a dominant cause of multi-drug resistant extra-intestinal infections in humans. The lineage has a three-clade phylogenetic structure of which clade C has gained resistance to multiple classes of antibiotics and is globally disseminated. As well as antimicrobial resistance, a number of virulence factors contribute to the success of ST131 clade C, including the production of capsule. Previous work on a limited number of strains has shown that the capsule operon in ST13...

— Potterill, I., Hall, R. J., Moran, R. A., Cummins, E. A., McNally, A. 2025-12-15 00:00:00

Characterization of new thermophilic antibiotic resistance markers

The genetic engineering of thermophilic bacteria is constrained by limited availability of thermostable antibiotic resistance markers for selection. Clostridium thermocellum, a promising candidate for consolidated bioprocessing of lignocellulosic biomass, requires reliable selection systems that function at elevated temperatures. Here, we systematically evaluated antibiotic susceptibility profiles and identified novel resistance markers for this thermophile through bioinformatic screening and...

— Souza Lopes, F., Vicentini, R., Yu Sin Kim, E., Ashok, N., Guss, A. M., Lynd, L. R., Walravens Bergamo, L., Olson, D. G. 2025-12-15 00:00:00

The influence of heteroresistance, growth and antibiotic selection in shaping the invasion dynamics of colistin resistant Pseudomonas aeruginosa

Heteroresistance, where a small subpopulation of phenotypically resistant cells coexists within an otherwise susceptible population, plays a critical role in bacterial survival during antibiotic exposure. Yet, its influence on the invasion success of genetically resistant strains remains poorly understood. In this study, we investigate the influence of bacterial heteroresistance, growth, and antibiotic selection on the outcome of an invasion experiment. We quantified the invasion dynamics of ...

— Rios, A. C. A., Pham, A. D., Knibbe, C. A. J., Rozen, D., van Hasselt, J. G. C., Aulin, L. B. S. 2025-12-15 00:00:00

Stochastic motility-adhesion switch within the E. coli K-12 strains revealed by gene expression clustering

Biofilm formation in Escherichia coli arises from regulatory programs that can diverge even among genetically identical cultures. Exploiting spontaneous replicate-to-replicate variation in E. coli K-12 MG1655, we mapped expression modules whose behavior tracks biofilm abundance across four genetic backgrounds: wild type; strain with deleted gene for hexuronate regulator UxuR duxuR; an uxuR translation-disrupted retaining locus-derived sRNAs (duxuR-tr), and strain with deleted gene for global ...

— Kaznadzey, A. D., Bessonova, T. A., Kuznetsova, U. D., Gelfand, M. S., Tutukina, M. N. 2025-12-15 00:00:00

Higher levels of antibiotic resistance are less competitive: the hidden ecological cost of no-metabolic cost resistance

Antibiotic resistance is often assumed to be constrained by fitness costs that limit the spread of highly resistant strains. Yet, many resistance mechanisms -- including enzymatic antibiotic degradation -- can arise with little or no metabolic cost, raising an important question: why is extreme resistance not more widespread? Here, we show that community-level interactions impose a hidden ecological cost on high resistance. By performing experiments with simple communities comprised of antibi...

— Wetherington, M., Copeland, R., Zhang, C., Hammer, B. K., Yunker, P. J. 2025-12-15 00:00:00

Structural Dynamics and Allosteric Communication of a SARS-Like Bat Coronavirus Spike Glycoprotein

SARS-like bat coronaviruses (CoVs) pose ongoing public health risks due to their zoonotic potential, making it important to understand the molecular pathways driving their evolution. We recently showed that SHC014-CoV can infect human cell lines in an ACE2-dependent manner after acquiring two spike ectodomain mutations (F294L and A835D). However, how the wild-type (WT) SHC014 spike differs dynamically from these mutants remains unclear. Here, we built fully glycosylated ectodomain models of W...

— Balogun, T., Kearns, F., Calvo-Tusell, C., Tse, A. L., Acreman, C. M., Casalino, L., Lasso, G., Miller, E. H., Chandran, K., McLellan, J. S., Amaro, R. E. 2025-12-15 00:00:00

SARS-CoV-2 Intra-host Variation Shows Evidence of Transmission and Convergent Evolution in a University Surveillance Cohort

Monitoring and understanding the transmission and evolution of SARS-CoV-2 remains a significant public health priority. Within-host genetic variation provides insight into viral evolution during infection and may help infer transmission events. In this study, we analyzed intra-host variation in SARS-CoV-2 genome sequences from Boston University's testing mandate. Focusing on intra-host single nucleotide variants (iSNVs), we inferred transmission events and assessed the selective forces shapin...

— Cavalli, L., Taylor, B. P., Schaeffer, B., Turcinovic, J., Connor, J. H., Hanage, W. P. 2025-12-15 00:00:00

Rotational settings quantize nucleosome movement by chromatin regulators

Proper nucleosome positioning is essential for gene regulation and genomic integrity. Regulated nucleosome assembly and positioning results from a need to protect DNA sequences genome-wide, constrained by the known intrinsic sequence preferences of histones. Current models posit that chromatin regulators override the intrinsic preferences to establish the nucleosome landscapes observed in vivo, implying minimal roles for DNA sequence in guiding nucleosomal structure in cells. In contrast, we ...

— La, V., Trouth, A., Ramani, V., Ramachandran, S. 2025-12-15 00:00:00

Centromeres and pericentromeric heterochromatin are accessible in living Schizosaccharomyces pombe cells

Chromatin is intrinsically repressive, limiting access to DNA, implying a major regulatory role. Studies with nuclei support this model. However, we have shown previously that genomic DNA is almost completely accessible in living budding yeast and human cells, except for centromeric chromatin. The fission yeast, Schizosaccharomyces pombe, possesses heterochromatin similar to mammalian heterochromatin at the pericentromeric repeats, telomeres and the silenced mating type loci. S. pombe heteroc...

— Panigrahi, L., Xu, Z., Clark, D. J. 2025-12-15 00:00:00

Male songbirds show higher coccidia oocyst burdens than femalesfollowing anthelmintic treatment

In wildlife research, wild-caught vertebrates are often given anti-parasitic drugs when brought into captivity to protect animal health and reduce confounding effects of parasitic infection on research outcomes. However, the impacts of antiparasitic drugs on non-target parasite taxa are understudied, especially regarding host sex. To help address this gap, we investigated the impact of an anthelmintic medication on a protozoan gut parasite by quantifying coccidia oocyst burden in the feces of...

— Talbott, K., Tysver, A., Wanamaker, S., Ketterson, E. 2025-12-15 00:00:00

Advances on the bacterial diversity and functionality of Platypus cylindrus - Quercus suber interaction

The ambrosia beetle Platypus cylindrus Fab. (Coleoptera: Curculionidae: Platypodinae) has been associated in Portugal with cork oak (Quercus suber) tree death since the 1980s. Although traditionally known as a secondary pest damaging stressed and dead trees, its aggressiveness changed over the last decades. Ambrosia beetle is an insect known for its interactions with several species of fungi aiming for the gain of biologic functions that facilitates its life cycle. How bacterial communities h...

— Nones, S., Simoes, F., Serra, O., Matos, J., Sousa, E. 2025-12-15 00:00:00

Mammalian Cells Integrate Endoplasmic Reticulum and Nuclear Envelope signals to time mitotic entry

Accurate cell division requires coordination between organelle organization and cell-cycle progression, but how architectural and functional cues from the endoplasmic reticulum (ER) and nuclear envelope (NE)-a continuous membrane network-interface with mitotic control remains unclear. Here, we demonstrate that mammalian cells integrate ER/NE structure and functions to regulate the onset and progression of mitosis. Perturbing ER function with diverse stressors causes a selective delay at the m...

— Shiozaki, Y., Codallos, N., Saik, N., Jenkins, D., Lara-Gonzalez, P., Shiau, A., Ullman, K., Niwa, M. 2025-12-15 00:00:00

Echolocation calls of some bat species in western Uganda

With the rise of accessible recording technology, passive acoustic monitoring can be an affordable and rapid way to assess species richness, even when individual animals cannot be captured due to regulatory or practical obstacles. Motivated by the relative lack of data and in partnership with the local populace, we recorded echolocation calls of freely-flying bats across six locations in rural western Uganda using opportunistic passive acoustic recordings. Frequency-modulated echolocation cal...

— Kloepper, L. N., Fry, R. N., Maliszewski, O., Hahn, R. S., Simmons, J. A., Simmons, A. M. 2025-12-15 00:00:00

A Critical Window of Maternal Temperature Effects on Weedy Rice Seed Dormancy

Seed dormancy is a critical trait for the survival and adaptation of agricultural weeds. The maternal temperature after flowering influences the post-dispersal response of progeny seeds, which adds layers of complexity to weed control management programs. Understanding when the maternal environment exerts its effect on seed dormancy provides valuable insights into plant fitness and weed management. In this study, we investigated weedy rice progeny seed responses to determine the sensitivity w...

— Auge, G., Nishikata, R., Imaizumi, T. 2025-12-15 00:00:00

Targeting granule initiation and amyloplast structure to create giant starch granules in wheat

Starch granule size influences the functional, digestive, and processing qualities of starch, but its genetic control in plants is poorly understood. Here, we demonstrate that both space and substrate constraints limit starch granule size in wheat and provide an approach to achieve substantial increases in granule size. Wheat starch typically contains large A-type and small B-type granules. To increase A-type granule size, we explored the effect of mutations in the plastid division component ...

— McNelly, R., Esch, L., Ngai, Q. Y., Pohan, K., Stringer, R., Fahy, B., Warren, F., Seung, D. 2025-12-15 00:00:00

Cellular consequences of non-ablative radiotherapy, a novel approach to ventricular tachycardias

Background. Radiotherapy (RT) with a single focused application of ionizing radiation (STAR) has been suggested as a non-invasive alternative to radiofrequency in ablating ventricular tachycardia (VT). Emerging data reveal that STAR may suppress VT without substrate destruction, by enhancing impulse conduction instead, through increased expression of NaV1.5 channels and connexin 43. Aims. To investigate electrophysiology and intracellular Ca2+ dynamics in cardiomyocytes (CMs) from mice subjec...

— Maniezzi, C., Busti, S., Maione, A. S., Sommariva, E., Florindi, C., De Ferrari, G. M., Lodola, F., Zaza, A. 2025-12-15 00:00:00

SpaCEy: Discovery of Functional Spatial Tissue Patterns by Association with Clinical Features Using Explainable Graph Neural Networks

Tissues are complex ecosystems tightly organized in space. This organization influences their function, and its alteration underpins multiple diseases. Spatial omics allows us to profile its molecular basis, but how to leverage these data to link spatial organization and molecular patterns to clinical practice remains a challenge. We present SpaCEy (SpatialClinicalExplainability), an explainable graph neural network that uncovers organizational tissue patterns predictive of clinical outcomes....

— Rifaioglu, A. S., Ervin, E. H., Sarigun, A., Germen, D., Bodenmiller, B., Tanevski, J., Saez-Rodriguez, J. 2025-12-15 00:00:00

Positional Scanning and Computational Modeling Reveal Determinants of Legumain Transpeptidase Activity

Legumains are cysteine proteases that, in addition to their canonical hydrolase function, can act as peptide ligases or transpeptidases. In humans, this activity becomes particularly relevant under pathophysiological conditions, where legumain relocalizes to near-neutral pH compartments favoring ligation/transpeptidation over hydrolysis. Here, we combined in vitro positional scanning with in silico substrate profiling to elucidate the substrate determinants governing human legumain-mediated p...

— Klaushofer, R., Dahms, S. O., Brandstetter, H., Dall, E. 2025-12-15 00:00:00

Benchmarking of duplex sequencing approaches to reveal somatic mutation landscapes

Detecting somatic mutations in normal tissues is challenging due to sequencing errors and the low allele fractions of post-zygotic variants. Duplex sequencing greatly reduces errors and can detect mutations at any allele fraction, but systematic, cross-platform comparisons are lacking. We present a comprehensive benchmarking of six duplex sequencing technologies used by the SMaHT Network: CODEC, CompDuplex-seq, HiDEF-seq, NanoSeq, ppmSeq, and VISTA-seq. We evaluated their performance using co...

— Zhang, Y., Viswanadham, V., Andreopoulos, M., Glodzik, D., Liu, R., Luquette, L., Jo, S.-Y., Narayan, A., Niu, M., Anderson, L., Brew, J., Chao, H., Cibulskis, C., Dong, G., Evani, U., Feng, W., Gronska-Peski, M., Helland, A., Hilal, N., Jabara, N., Jin, H., Li, N., Manam, M., Mallett, S., Runnels, A., Scharlee, C., Smith, C., The SMaHT Duplex Sequencing Working Group,, Shao, D., Walsh, C., Adalsteinsson, V., Germer, S., Gibbs, R., Choudhury, S., Doddapaneni, H., Evrony, G., Zong, C., Coorens... 2025-12-15 00:00:00

Multi-Omics Reprogramming Drives a Counterintuitive Reversal of Disease Susceptibility During Ageing

Ageing is a progressive and irreversible biological process characterized by the deterioration of physiological functions and increased vulnerability to mortality. Although extensively studied in vertebrates, ageing in long-lived invertebrates remains comparatively unexplored. While ageing typically leads to greater susceptibility to infectious diseases, a striking and unexpected reversal was identified in oysters: older oysters exhibit markedly increased tolerance to the Pacific Oyster Morta...

— Valdivieso, A., Duperret, L., Petton, B., Courtay, G., Romatif, O., POUZADOUX, J., HENRY, S., Turtoi, A., Toulza, E., Lagorce, A., Degremont, L., Morga, B., Cosseau, C., Pernet, F., Mitta, G., Vidal-Dupiol, J. 2025-12-15 00:00:00

Rapid identification of microbial pathogens and antimicrobial resistance from bloodstream infections using long-read sequencing

The gold standard for bloodstream infection (BSI) diagnostics involves culturing positive blood cultures (BC) using phenotypic methods for organism identification and antimicrobial resistance (AMR) testing, which can take up to five days. However, it is crucial to optimize antimicrobial therapy as soon as possible to reduce morbidity and mortality. We present a novel laboratory and bioinformatic workflow to rapidly identify bacterial and fungal organisms and AMR determinants from positive BCs...

— Lerminiaux, N., Fakharuddin, K., Adam, H. J., Bharat, A., Golding, G. R., Martin, I., Mulvey, M., Mataseje, L. 2025-12-15 00:00:00

Arthropod predator nutrient content changes with crop sowing period with implications for biocontrol

Conservation biocontrol is crucial for crop pest management, but the impact of agricultural management practices on natural enemies of crop pests is poorly characterised. The timing of crop sowing could impact arthropod communities by altering basal resource availability and quality, manifesting in altered nutrient availability and cascading impacts to natural enemy fitness and function. This study aims to understand these potential modifiers of conservation biocontrol, by investigating how t...

— Christopher, R., Wright, R., Windsor, F. M., Cuff, J. P. 2025-12-15 00:00:00

Density dependence affects population recovery following an epidemic

Current epidemiological models for the regulation of host populations by pathogens suggest that the reduction in the host population is largest shortly after the epidemic phase and that the host population partly recovers in the subsequent approach to endemicity. We find that this conventional view is not robust to a simple, biologically motivated addition: density-dependent population regulation (homeostasis). While rapid homeostasis typically enables a population rebound after the initial p...

— Antia, R., Bull, J. J. 2025-12-15 00:00:00

Pancreatic δ-cells are resistant to auto- and paracrine inhibition in human type-2 diabetes

Somatostatin secretion from pancreatic {delta}-cells inhibits nearby - and {beta}-cells, and tunes the body's glycemic set-point. The role of {delta}-cells in diabetes remains unclear, in part due to the difficulty separating intrinsic regulation from intra-islet paracrine effects. Here we compared the function of isolated {delta}-cells of cadaveric non-diabetic and type-2 diabetic donors, by single cell TIRF-microscopy and electrophysiology. Elevated glucose stimulated exocytosis of somatost...

— Omar-Hmeadi, M., Matuseviciene, L., Liu, L., Lund, P. E., Barg, S. 2025-12-15 00:00:00

Membrane-associated periodic skeleton regulates major forms of endocytosis in neurons through a signaling-driven positive feedback loop

Endocytosis enables neurons to internalize molecules, maintaining homeostasis and responsiveness. The neuronal membrane-associated periodic skeleton (MPS), an actin-spectrin-based cytoskeletal lattice, is known to restrict clathrin-mediated endocytosis (CME) in axons, but its broader role in other neuronal compartments and endocytic pathways remains unclear. Here, we show that all four major endocytic pathways, CME, caveolin-, flotillin-, and fast endophilin-mediated endocytosis, are spatiall...

— Fei, J., Zheng, Y., LaLonde, C., Tao, Y., Zhou, R. 2025-12-15 00:00:00

Alignment of Artificial Neural Networks with Human Eye Movement Patterns in Facial Expression Recognition

Artificial neural networks (ANNs) have become powerful tools for modeling human perception and behavior, yet it remains unclear if they resemble the sequential eye movement strategies humans employ during visual processing. Human studies demonstrate that the first two fixations play distinct roles in face processing: the initial fixation (Fix I) captures global configurational information, while the second (Fix II) targets local diagnostic details, with the two working collaboratively to supp...

— Liu, M., Wang, L. 2025-12-15 00:00:00