The California serogroup (CSG) of orthobunyaviruses includes neuroinvasive viruses with varying pathogenicity. La Crosse virus (LACV) is a leading cause of pediatric arboviral encephalitis in the USA, while Inkoo virus (INKV) is widespread in Northern Europe but rarely causes disease. The reassortment potential of CSG viruses raises concerns about emerging virulent strains and highlights the […]
Improved adenine-HPLC method for quantifying yeast based on cellular DNA content
Accurate quantification of fungi is important for a myriad of applications but remains challenging. Previously, we demonstrated that an approach called the adenine-HPLC method can quantify bacteria, including those with aggregating properties that are difficult to quantify using conventional methods, by measuring cellular adenine derived from DNA and converting the adenine amount to genome copy […]
RepliCNN: High-resolution inference of the DNA replication program from strand-specific 3′ DNA end sequencing
During S phase, the genome is replicated in a tightly regulated spatiotemporal order described as DNA replication timing (RT). Discontinuous lagging-strand synthesis produces Okazaki fragments whose strand-specific distribution reflects replication dynamics. Here, we present RepliCNN, a deep learning framework based on one-dimensional convolutional neural networks to predict RT from Okazaki fragment distributions obtained from strand-specific […]
Enkephalin Gates D2-MSN Disinhibition of the Ventral Pallidum During Cocaine Abstinence
Abstinence from repeated cocaine exposure is associated with reduced GABA release from striatal medium spiny neurons that express D2 dopamine receptors (D2-MSN) and project to the ventral pallidum (VP). As a consequence, VP principle neuronal activity is increased and drives cocaine seeking. Abstinence from cocaine is also associated with increased expression of enkephalin in D2-MSNs. […]
Structural Basis of Serine Protease Inhibition by Antibodies from Biased Fab Phage-Display Libraries
Biased Fab phage-display libraries were designed to determine whether inhibitory CDR H3 motifs from potent anti-matriptase antibodies could be transferred to target homologous serine proteases. Using reverse-binding and substrate-like H3 motifs from parental clones A11 and E2 as templates, six synthetic libraries with 1010 diversity were constructed. Selection against matriptase identified sixteen inhibitors with sub-100~nM […]
ISG15-USP18 signaling restrains viperin-dependent metabolic antiviral restriction
Type I interferon (IFN-I) responses are tightly regulated to balance antiviral defense with cellular homeostasis. In humans, interferon-stimulated gene 15 (ISG15) functions as a critical negative regulator of IFN-I signaling by stabilizing the IFN negative regulator USP18, yet the functional consequences of ISG15 deficiency remain elusive. Here, we show that the loss of ISG15 exaggerates […]
PgaR is a positive regulator of the pgaABCD biosynthetic operon in Klebsiella pneumoniae
The biosynthetic locus encoding the exopolysaccharide poly-N-acetyl-glucosamine (PNAG) is widely conserved across bacteria, including the WHO critical-priority pathogen Klebsiella pneumoniae (Kp). In Kp, PNAG synthesis is mediated by the pgaABCD operon, yet its lineage-specific regulation remains incompletely defined. Using a comparative genomics approach to interrogate the pgaABCD locus across the high-risk clonal Kp complex 258 […]
Profiling of DNA-methylation signatures in human ILCs during homeostasis and allergic disease
DNA methylation is a stable epigenetic mark that critically influences the phenotype of immune cells. Identifying differentially methylated regions within immune cell lineages supports their phenotypic and functional characterization, leading to a better understanding of lineage-specific transcriptional regulation. Here, we performed a genome-wide methylation analysis of human innate lymphoid cells (ILCs), which allowed us to […]
Life in sediments fosters ‘sexual’ speciation in Shewanella baltica
Understanding how intra- and interspecific differentiation arises in natural microbial populations is central to explaining the processes that drive bacterial evolution. Motivated by the co-occurrence of several genospecies closely related to Shewanella baltica in Baltic Sea sediments, we investigated the genomic structure of this species complex across fine spatial scales. Here, we analyzed 112 genome […]
Marine bacterial resistomes integrate ecological adaptation with anthropogenic amplification: genome-resolved insight along a gradient of human impact
Antibiotic resistance genes (ARGs) are ubiquitous in marine environments, yet whether their distribution primarily reflects anthropogenic pollution or intrinsic ecological functions remains unresolved. We used genome-resolved metagenomics to characterize resistomes in 371 genomic operational taxonomic units (gOTUs) across a gradient of human impact: the heavily impacted Baltic Sea, the moderately impacted North Sea, and the […]
Genome-wide mapping of gene essentiality in Pseudomonas chlororaphis ATCC 9446 using transposon mutagenesis.
Pseudomonas chlororaphis ATCC 9446 is a non-pathogenic rhizobacterium with biotechnological relevance as a biocontrol agent and a promising chassis for synthetic biology. Understanding which genes are strictly required for survival is fundamental to both bacterial physiology and chassis engineering. Here, we generate a genome-wide map of genetic essentiality for P. chlororaphis using high-density Random Barcoded […]
Mitochondrial DNA Variation in the D-LOOP and ND Loci identified in the Kenyan Population: Potential Implications for precision Oncology
Background: Precision oncology is predominantly focused on nuclear genomic alterations, while mitochondrial DNA (mtDNA) variation remains largely excluded from routine pharmacogenomic testing. However, mitochondria regulate oxidative phosphorylation (OXPHOS), reactive oxygen species (ROS) production, apoptosis, and metabolic reprogramming pathways central to chemotherapy response. Methods: 468 Complete mitochondrial genomes from Kenyan individuals representing diverse ethnolinguistic groups were […]