Novo Nordisk Foundation

A phosphoproteome atlas of human cell lines reveals the landscape of kinase activity

Abstract Protein phosphorylation orchestrates cellular signaling and controls most biological processes, with its dysregulation driving diseases, notably cancer. Comprehensive, high-throughput phosphoproteomics remains limited by detection sensitivity, data completeness and compu...

AI-based characterization of Alzheimer’s disease phenotypes from population-scale single-cell data

The complexity of Alzheimer’s disease (AD) manifests in diverse clinical phenotypes, including cognitive impairment and neuropsychiatric symptoms. However, the etiology of these phenotypes remains elusive. To address this, the PsychAD project generated a population-level single-n...

Single-nucleus transcriptome-wide association study of human brain disorders

Abstract Common brain disorders impose a substantial health burden, but localizing their genetic risk in the brain remains challenging 1 . Although genome-wide association studies have identified numerous loci associated with neuropsychiatric and neurodegenerative disorders, many...

Lifespan single-cell transcriptomic atlas of the human prefrontal cortex

The human brain undergoes profound changes from early development through late adulthood, shaping cognition, behaviour and vulnerability to disease1,2. Understanding how these changes are organized within specific brain regions and cell types is essential for interpreting normal...

Single-cell atlas of transcriptomic vulnerability across brain disorders

Abstract Neurodegenerative and neuropsychiatric diseases impose a considerable societal and public health burden. However, our understanding of the molecular mechanisms underlying these highly complex conditions remains limited 1,2 . Here, to gain deeper insights into the aetiolo...

Personalized single-cell transcriptomics reveals molecular diversity in Alzheimer’s disease

Alzheimer’s disease (AD) is highly heterogeneous and driven by diverse molecular and cellular mechanisms. Functional genomics investigates these mechanisms from genetic variants to gene expression and regulation. We performed personalized functional genomics analysis on populatio...

Single-nucleus atlas of cell-type specific genetic regulation in the human brain

Abstract Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of th...

Scalable clinical proteomics from DNA/RNA extraction flowthroughs enables integrated proteogenomic profiling from a single cancer biopsy

Abstract Background Precision oncology has largely relied on genomic and transcriptomic sequencing to guide therapy selection in patients with advanced cancer. However, these molecular layers do not fully capture the functional state of tumors, as proteins largely represent the a...

Oral health and oral microbiota composition in patients with Parkinson’s disease: a case‒control study

Introduction Parkinson’s disease (PD) is associated with motor and non-motor dysfunctions that may influence oral homeostasis. An altered microbiota has been linked to PD, yet oral microbial changes remain poorly characterized. This case‒control study aimed to determine if the or...

Extending single-cell proteomics from HeLa to small primary human immune cells

Abstract Single-cell proteomics (SCP) holds the promise of decoding cellular heterogeneity at the functional level, yet achieving deep and reproducible proteome coverage from individual cells has remained a formidable challenge. Here, we establish a high-sensitivity, label-free S...

Parallel regulation of tissue morphogenesis and cell fate specification by RAR:RXR signalling during pancreas formation

During embryogenesis, morphologically diverse epithelial organs bud from different regions of the embryonic gut. The unique features of each nascent organ result from distinct cell fate specification and morphogenetic events elicited by organ-inducing cues. Retinoic acid is a pow...

Sleep Duration and Metabolic Biomarkers During Pregnancy: A Longitudinal Study in a Multiracial Cohort

Abstract Objective: To examine associations between sleep duration and metabolic biomarkers in pregnant women. Methods: This nested case-control study involved 321 pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth...

Intravenous Oxytocin Does Not Affect Glucose‐Regulating Hormones or Markers of Bone Turnover During Graded Glucose Infusion in Healthy Men

AIM: Oxytocin has been proposed to exert glucose-stabilising effects via modulation of pancreatic hormone secretion and to play a role in bone homeostasis. However, human data under controlled conditions are limited. We investigated the effects of intravenously infused oxytocin d...

Cullin 3 ubiquitin ligase regulates redox defense and metabolic programs in proximal tubule cells

Abstract Background Chronic kidney disease (CKD) is characterized by proximal tubule (PT) stress, oxidative injury, and metabolic dysfunction. Human kidney single-nucleus RNA-sequencing (snRNA-seq) identified enrichment of ubiquitin-dependent protein catabolic processes in injure...

Activation of transposable elements is linked to a region- and cell type–specific interferon response in Parkinson’s disease

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder involving a neuroinflammatory response, the cause of which remains unclear. Transposable elements (TE) have been linked to inflammation, but their potential role in PD remains unexplored. Using bulk- and single-nuc...

Cardiolipin deficiency disrupts electron transport chain and drives steatohepatitis

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive disorder marked by lipid accumulation, leading to metabolic dysfunction-associated steatohepatitis (MASH). A key feature of the transition to MASH involves oxidative stress resulting from defects in...

Sex- and fiber type-specific remodeling of the muscle proteome implicates CSRP3 in resistance training-induced hypertrophy

Skeletal muscle hypertrophy is a hallmark of resistance training that improves health and longevity. However, despite physiological differences between sexes and fiber types, the underlying proteome changes with resistance training have not been studied in a sex- and fiber type-s...

Single-cell profiling identifies obesity-disrupted brain glucose sensing

Abstract Neuronal nutrient sensing in the hypothalamus and brainstem is thought to regulate energy and glucose homeostasis, yet how these brain regions respond to elevated adiposity or blood glucose remains unclear. We performed single-nucleus RNA-sequencing on 75,787 cells from...

Response-Tailored or Standard-Duration Antibiotic Treatment for Infective Endocarditis

BACKGROUND: In patients with infective endocarditis on the left side of the heart, the current recommendation of up to 6 weeks of antibiotic therapy is based largely on expert consensus opinion. Whether a clinical response-tailored antibiotic management strategy can shorten treat...

Seaweed (Saccharina latissima) modulates the microbiome composition during fecal fermentation with limited effect of common processing methods

Seaweed fibers show promising effects on gut health, but it is unclear if processing of whole seaweed changes the nutrient accessibility for gut microbiota. This study investigated the effects of processed Saccharina latissima on the fecal microbiome composition and metabolic act...