Although wetlands are increasingly recognized as important contributors to the global methane budget, the microorganisms and processes involved methane cycling are poorly characterized, particularly in coastal brackish and saline systems. Here, we investigated microbial and geochemical factors contributing to methane dynamics in three coastal wetlands with different salinities, dominant vegetation types, and soil chemical characteristics. […]
Knowledge Inclusive Machine Learning for Disease Gene Prioritisation
The predictive performance of machine learning models depends on the context available to them. In disease gene prioritisation, this context comprises two forms: specific context from sample-level experimental data, such as gene expression and protein-protein interaction networks, and general context from accumulated and curated biological knowledge capturing established relationships among genes, diseases, and pathways. Neither […]
Phage terminase recognition by the bacterial immune sensors Avs2 and Upx
Prokaryotes employ diverse defense strategies to detect and halt the progression of phage infection. Multiple defense systems sense phage proteins through direct binding, including antiviral STAND NTPases (Avs), which oligomerize upon target recognition to induce programmed cell death. The widespread Avs2 family was previously shown to detect the large terminase subunit of tailed phages, but […]
Structural Insights into the Coupling Mechanism of Vectorial CO2 Uptake by DAB1
CO2 transporters enable bacterial carbon-concentrating mechanisms by catalyzing directional hydration of CO2, yet the basis of this vectorial carbonic anhydrase (CA) activity remains an open question. We used cryo-EM to determine the structure of the DAB1 complex from Thermocrinis albus to 2.13 [A], revealing a heterotrimer in which a deeply buried beta-CA active site in […]
Bipartite DNA binding domain of transcription factor BCL11B binds clustered short DNA sequence motifs
B-cell leukemia/lymphoma 11B (BCL11B), despite its name, is a key regulator of T-cell development, specification, and T-cell malignancies. BCL11B contains a bipartite DNA binding domain composed of two C2H2 zinc finger arrays: low-affinity ZF2-3 and high affinity ZF4-6. These arrays function as homotypic modules that recognize similar six-nucleotide motifs, TG(N)CC(C/T/A), as seven of the eight […]
MissAlignment Teaches Itself Better Cryo-ET Tilt-Series Alignment by Making It Worse
Cryo-electron tomography (cryo-ET) visualizes cellular environments in a near-native state at macromolecular resolution. Accurate alignment of the tilted projection images is essential for data interpretation, yet existing reference-free algorithms often fail due to limited information overlap between images and inaccurate assumptions about the sample. Human experts, however, can easily recognize the misalignment left by these […]
Systematic benchmarking of small variant calling pipelines for long-read RNA sequencing data
Background: Long-read RNA sequencing (lrRNA-seq) enables transcript-resolved variant detection, but systematic and neutral evaluations of small variants calling pipelines remain limited. The performance of existing tools across sequencing technologies, alignment strategy, variant caller choice, genomic contexts and downstream haplotype phasing is not fully understood. Results: Here, we systematically benchmark four lrRNA-seq variant callers (Clair3-RNA, DeepVariant, […]
Solid-state fermentation of oyster mushroom by-products using Neurospora crassa: a sustainable approach for the development of novel meat analogues
Mushroom production generates large amounts of by-products, particularly stipes, which can represent up to half of the fruiting body biomass. Due to their similar composition to mushroom caps, these residues represent a promising substrate for the development of value-added foods. In this study, oyster mushroom stipes were used as a substrate for solid-state fermentation (SSF) […]
Type 1-polarized DC immunotherapeutic contains heterogeneous populations with IL-12p70 production restricted to a rare subset
Monocyte-derived DC therapies programmed for robust IL-12p70 production have been associated with favorable outcomes in cancer clinical trials. However, clinical responses remain inconsistent even under standardized protocols, and the cellular basis for this variability is unknown. We leveraged single-cell multiomics to characterize two widely used DC platforms, the high-IL-12p70-producing alpha-Type-1-polarized DC (DC1) and the IL-12p70-deficient […]
β-lactam antibiotics trigger TLR2-dependent Jarisch-Herxheimer reaction in leptospirosis: bacteriostatic antibiotics offer a safer alternative
Leptospirosis is a reemerging neglected zoonotic disease causing 1 million cases and 60,000 deaths annually. Antibiotic treatment can trigger a detrimental inflammatory Jarisch-Herxheimer reaction (JHR). We investigated the effects and mechanisms of different antibiotics and consequences of JHR in leptospirosis. In a mouse model of severe infection and in healthy human whole-blood infected with bioluminescent […]
Integrative phenotypic and transcriptomic validation of an alveolar-like macrophage model reveals early host-pathogen dynamics during Aspergillus fumigatus infection
The saprophytic mold Aspergillus fumigatus produces small (2-3 microm) airborne spores (conidia) that can reach the lung alveoli upon inhalation. There, they encounter the surfactant-rich environment of the alveolar epithelium and initiate swelling and germination. Primary alveolar macrophages are essential for the rapid clearance of conidia and maintenance of pulmonary homeostasis. However, A. fumigatus remains […]
A growth-survival trade-off quantitatively predicts microbial selection under periodic disinfection
Microbial populations frequently experience periodic lethal stresses from natural and anthropogenic sources, including routine disinfection in clinical, industrial, and domestic environments. However, periodic disinfection can rapidly select for tolerant strains with increased survival but reduced growth during permissive conditions, creating a trade-off that shapes competitive outcomes in microbial communities. Here, we develop a mathematical framework […]