Research Network (United States)

Validating Type 2 Diabetes Diagnoses Across the Madrid Hospital Network: Evidence for Secondary Use of the CMBD in the European Health Data Space

Background/Objectives: Hospital discharge data are increasingly reused for research and within health data spaces, but their value depends on accurate diagnostic coding. The validity of type 2 diabetes mellitus (T2DM) coding in the Spanish hospital discharge database (CMBD) had n...

Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra

Recent studies have implicated dopaminergic signaling within the substantia nigra pars reticulata (SNr) in the emergence of Parkinsonian motor deficits. To better understand the mechanisms underlying this dependence, the ability of dopamine to modulate SNr neuron activity was stu...

From Trials to Treatment: Current Evidence Supporting Faricimab Use in nAMD and DME

Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) are leading causes of visual impairment and require long-term intravitreal anti-vascular endothelial growth factor (VEGF) therapy. However, treatment burden and suboptimal real-world outcomes rem...

Reconstitution of multistep recruitment of ULK1 to membranes in autophagy

Abstract The Human ULK1 autophagy-initiating complex consists of ULK1, FIP200, and the HORMA domain heterodimer ATG13:ATG101. PI3P is essential to recruit ULK1C to membranes for ULK1, but ULK1C subunits do not contain PI3P-binding domains. Here we show that the ATG13:ATG101 dimer...

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...

A lipid transfer-dependent feedback loop activates ATG9A compartments in autophagy initiation

Abstract Autophagy degrades cellular material by sequestering it within autophagosomes, which form de novo from precursors called phagophores. Phagophore assembly and expansion require ATG9A-positive seed compartments, the lipid transfer protein ATG2A, and the class III phosphati...

Association of blood-pressure time-in-therapeutic range with morbidity and mortality in hypertensive patients: a retrospective cohort study in the community setting

Abstract Background Hypertension is one of the leading modifiable risk factors for cardiovascular disease. This study assessed the association between good blood pressure control (GBPC), measured by time in therapeutic range (TTR) during the first year after hypertension diagnosi...

Fluorescence-Gated Flow Cytometry Approach for Measuring Lipid Flippase Activity in Mammalian Cells

Abstract P4‑ATPase lipid flippases establish transbilayer lipid asymmetry in eukaryotic membranes, with increasing evidence indicating a role for interacting partners in regulating flippase activity. However, assessing interactor‑dependent effects on flippase activity in mammalia...

Mitochondrial bioenergetic remodeling underlies fingolimod-induced immunometabolic adaptation in multiple sclerosis

Mitochondrial dysfunction and immune cell metabolic reprogramming are central mechanisms driving the pathogenesis and progression of multiple sclerosis (MS). Fingolimod (FTY720), a sphingosine-1-phosphate analog widely used in MS, limits lymphocyte egress from lymphoid organs; ho...