Although nicotinamide adenine dinucleotide (NAD) metabolism is fundamental for cancer cell survival, the role of the de novo NAD biosynthetic pathway, particularly in non-small cell lung cancer (NSCLC), remains largely unknown. Here, we describe a non-canonical role for the rate-limiting enzyme in de novo NAD+ biosynthesis, quinolinate phosphoribosyltransferase (QPRT), in NSCLC progression. We show that […]
Patient characteristics associated with participation in cardiorespiratory exercise during stroke rehabilitation: a multisite observational cohort study
Objectives: Among individuals attending stroke rehabilitation, we aimed to determine the proportion who participated in cardiorespiratory exercise, identify patient characteristics predicting participation, and describe exercise characteristics. Design, setting, and participants: This was an observational cohort study involving all patients admitted to four stroke rehabilitation centres in Ontario, Canada, during March or October 2019, or over […]
Multimodal Wearable and Survey Data Reveal Distinct Physiologic Profiles in Hypermobile-Ehlers Danlos Syndrome for Screening Advancements
Hypermobile Ehlers-Danlos Syndrome (hEDS) is a genetic connective tissue disorder characterized by hypermobile joints, chronic pain, fatigue, brain fog, orthostatic intolerance, and GI symptoms and dysmotility. Its heterogeneous presentation contributes to poor quality of life, inappropriate interventions, and prolonged diagnostic delays, often up to 10 years. This study primarily aimed to determine if physiological signals […]
Inflammatory memory disables a DDR1 degradation checkpoint to enable pancreatic cancer growth
Inflammation and stroma remodeling regulate pancreatic ductal adenocarcinoma (PDAC), but how or if these cues are integrated at the molecular level remains unclear. Here, we identify a metabolic checkpoint that controls the stability of the collagen receptor DDR1, and subsequent tumorigenesis. We show that defective Col-I remodeling deprives PDAC cells of the high affinity DDR1 […]
Systemic and tumor intrinsic expansion of FCRL5 expressing B cells associates with poor response to Bacillus Calmette-Guerin immunotherapy in patients with non-muscle invasive bladder cancer
Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy remains the standard treatment for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC), yet more than half of the patients do not respond and experience recurrence or progression. BCG induced humoral immune responses remain poorly defined in patients with NMIBC. Building upon our previous findings showing the pathogenic role of […]
Socotra Cormorants in the Arabian Gulf represent a large, but isolated population with low genetic diversity
The Socotra Cormorant (Phalacrocorax nigrogularis) is a threatened seabird endemic to the coastal areas of the Arabian Gulf and the Arabian Sea, two regions separated by the Strait of Hormuz. Conserving threatened species requires clear delineation of population boundaries and the evaluation of genetic diversity. However, information on population structure and genetic variation, necessary for […]
Gallium induces cytotoxicity through disruption of DNA synthesis rather than ferroptosis
Background: Gallium (Ga) is a promising anti-tumor agent; however, its precise molecular targets in osteosarcoma remain debated. While current paradigms largely attribute its toxicity to reactive oxygen species (ROS) and ferroptosis, understanding its true mechanism is essential for overcoming therapeutic resistance. This highlights the need for interdisciplinary approaches, such as metabolomics, to unveil novel vulnerabilities […]
Wind pattern oscillations explain seabird movements at-sea: a nested multiscale approach
Wind has a strong influence on the flight characteristics, movements, energetics, demography, life-history traits and biogeography of flying animals. With climate change affecting atmospheric circulation patterns at different time scales, understanding the links between wind and animal movements is crucial for predicting its impact on flying biodiversity. Most studies on the relationship between wind and […]
Nonuniform scaling of cerebellar cortical-nuclear architecture across primates revealed by cross-species atlases
The cerebellum shapes distributed motor and association networks through precisely organized pathways linking the cerebellar cortex to the deep cerebellar nuclei (DCN), its principal output structures. Whether these cortical and nuclear compartments scale proportionally across primates and how their relative expansion influences large-scale brain organization remains unclear. We generated multimodal, high-resolution cross-species 3D cerebellar atlases […]
The fate of mutations on Y chromosomes andautosomes: a unified Wright-Fisher frameworkaccounting for segregation time
Understanding how mutations evolve on Y chromosomes is central to explaining the origin, diversity and persistence of sex chromosomes. Mutations occurring on the Y chromosome in sexual populations experience selective dynamics that differ markedly from those on autosomes, due to a reduced effective population size and the presence of large non-recombining regions containing alleles maintained […]
Activation of DMH GABAergic neurons, but not local GABAergic AgRP neurons, attenuates chronic stress-induced POMC neuron hyperactivity
Identifying the neural circuits engaged and reshaped by chronic stress is critical for understanding how adaptive responses shift to maladaptive behaviors that contribute to stress-related disorders. Our previous work demonstrates that chronic unpredictable stress (CUS) induces a persistent increase in the firing activity of proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC). This hyperactivity is […]
Sphingolipid remodelling in SPT-related neuropathies
Sphingolipid homeostasis is critical for neuronal structural and functional integrity in the central and peripheral nervous systems. The rate-limiting enzyme of this pathway, serine-palmitoyltransferase (SPT), establishes the metabolic entry point into sphingolipid biosynthesis. Mutations in the SPT subunits, SPTLC1 and SPTLC2 lead to contrasting disease phenotypes in patients, including amyotrophic lateral sclerosis (ALS) and hereditary […]