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 […]
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 […]
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 […]
One-pot parallel Sidewinder construction from oligo pools
Reliable and cost effective de novo DNA production has become central to studying and engineering biology. Short synthetic single-stranded DNA oligo pools offer substantially reduced costs at the sacrifice of yield and individual oligo isolation. Efficiently constructing longer synthetic double-stranded DNA molecules from oligo pools as the input has remained an engineering challenge with the […]
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 […]
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 […]
Are entirely virus-free CAR T cells as good as lentiviral transduced universal cells?
Chimeric Antigen Receptor (CAR) T cells are now established as therapies for some haematological malignancies. While lentiviral or gamma-retroviral vectors are commonly used for CAR delivery due to their efficiency and stable integration, supply constraints have created bottlenecks to wider applications and access. Alternatively, genome editing tools such as CRISPR-Cas9 can insert CAR genes by […]
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 […]
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) […]
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 […]
Oxygen gradients reshape cross-feeding through emergent spatial organization of gut commensal bacteria
Microbial interactions unfold within environments structured by physical transport and chemical gradients. Yet most mechanistic studies rely on well-mixed systems that mask the reciprocal influences of environmental heterogeneity on metabolism and ecology. Here, we investigate how the physical environment modulates the interaction between the gut commensal Bacteroides thetaiotaomicron and Escherichia coli. In anoxic liquid culture, […]
The Leray-XT COI primer pair is not suitable for observing ciliates and radiolarians
The Leray-XT primer pair has been widely used to amplify the mitochondrial cytochrome c oxidase subunit I (COI) gene from animals. In some marine metabarcoding studies, protists have also been amplified and sequenced using these primers. Here, we ask if the Leray-XT COI primer pair is suitable for observing ciliates and radiolarians, which are numerically […]