Male meiotic prophase I features a major transition from leptotene/zygotene (LZ) to pachytene/diplotene (PD) spermatocytes, accompanied by rapid growth and extensive transcriptional remodeling. Using stage-resolved purification of spermatogenic populations integrated with Seahorse respirometry, proteomics/metabolomics, and stable-isotope tracing, we define metabolic programs across this transition. LZ spermatocytes show little oxidative response to glucose or lactate and […]
Energy Flux Regulates Cell Death Induced by California Serogroup Orthobunyaviruses
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 […]
Interactions between inbreeding, fitness and the bacterial microbiome in Aedes aegypti mosquitoes
Laboratory and field populations of insects can experience a decline in fitness and loss of genetic diversity due to inbreeding depression and genetic drift, respectively. Matings among related individuals and small population size may also influence insect host microbiomes with consequences for fitness. In the dengue vector mosquito, Aedes aegypti, the bacterial microbiome is largely […]
EBEx: an Ensemble-Based Explainable Framework for Gene Calling in Heterogeneous Diseases
Complex and clinically heterogeneous diseases pose significant challenges for gene prioritisation and patient stratification, as relevant genes often show weak or context-specific signals and transcriptomic datasets are limited in size. These limitations hinder the discovery of robust molecular signatures using traditional case-control approaches and motivate computational pipelines capable of capturing molecular diversity. Here, we present […]
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 […]
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 […]
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 […]
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. […]
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 […]
A potential role for acyl-phosphate in the coordination of phospholipid and lipopolysaccharide synthesis in Escherichia coli
The envelope of Gram-negative bacteria like Escherichia coli is multilayered with two membranes sandwiching a peptidoglycan cell wall. The inner membrane is a typical phospholipid bilayer whereas the outer membrane is asymmetric with phospholipids in the inner leaflet and lipopolysaccharide (LPS) in the outer leaflet. We recently discovered that inactivation of the conserved peptidoglycan synthesis […]
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 […]