National Institute of Neurological Disorders and Stroke

Exploring transcriptomic and genomic latent variable correction approaches in differential expression analysis

Abstract Background Differential expression analysis is a central tool for studying the biological processes altered in human diseases via transcriptomic signatures. However, transcriptomic datasets are systematically confounded by latent variables from two distinct sources: unme...

Autologous haematopoietic stem cell transplantation affects paramagnetic rim lesions in multiple sclerosis

Background: Available literature shows a marginal or no effect of disease-modifying therapies on paramagnetic rim lesions (PRLs), a promising magnetic resonance imaging marker of chronic inflammation in multiple sclerosis. Objective: To investigate longitudinal changes in PRL cou...

Neurodegenerative disease risk associated with gene expression in peripheral monocytes across ancestries

Abstract It is hypothesised that peripheral immune states responding to regional environmental triggers contribute to central neurodegeneration. Region-specific genetic selection pressures require this hypothesis to be assessed in an ancestry-specific manner. Here, we utilise gen...

ERVmancer: a phylogeny-guided framework for decoding human endogenous retrovirus regulatory mechanisms in health and disease

Human endogenous retroviruses (HERVs), remnants of ancient infections, comprise approximately 8% of the human genome and influence development, immunity, and cancer. Their repetitive sequences complicate short-read analysis because reads often cannot be assigned to individual loc...

Neocortical long-range inhibition promotes cortical synchrony and sleep

Abstract Sleep and wakefulness are associated with distinct cortical patterns of rhythmic activity 1 . During low-arousal states such as slow-wave sleep, synchronous low-frequency rhythms dominate activity across widespread cortical regions. Although inhibitory neurons are increa...

The role of chloride ions in serotonin transport

Abstract The human serotonin (5-HT + ) transporter SERT facilitates 5-HT + transport into cells by coupling it to Na + symport and K + antiport. Although extracellular Cl − is also essential for transport, Cl − co-transport has been disputed, raising questions about the role of C...

Functional Activity of TDP-43: A Direct Biomarker for ALS

TDP-43 dysfunction is a defining feature of amyotrophic lateral sclerosis (ALS), yet no biofluid biomarker directly measures its functional activity. We developed a serum-based homogeneous time-resolved FRET (hTR-FRET) assay that quantifies TDP-43 RNA binding activity using synth...

Altered thalamo–prefrontal synchrony dynamics during spatial working memory task performance in a SETD1A loss-of-function mouse model of schizophrenia predisposition

ABSTRACT Schizophrenia is associated with profound working memory deficits, for which there are no approved treatments. Rare heterozygous null mutations in SETD1A , a gene encoding a key epigenetic regulatory protein, have been definitively linked to increased risk for schizophre...

Endothelial Cell Proteins as Biomarkers in Susac Syndrome

ABSTRACT Objective Susac syndrome (SS) is a rare CD8 + T cell–mediated microangiopathy affecting the brain, retina, and auditory labyrinth. Endothelial injury is thought to be a central mechanism; however, no circulating disease biomarkers are known. We performed targeted proteom...

Duration of Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest

Importance Therapeutic hypothermia is widely used for neuroprotection following cardiac arrest, but clinical trials have not consistently demonstrated improved neurological outcomes, and the optimal duration of cooling remains uncertain. Objective To determine the duration of the...