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Oligodendrocyte progenitor cells (OPCs) are highly dynamic, widely distributed glial cells of the central nervous system responsible for generating myelinating oligodendrocytes throughout life. However, the rates of OPC proliferation and differentiation decline dramatically with aging, which may impair homeostasis, remyelination and adaptive myelination during learning. To determine how aging influences OPCs, we generated a transgenic mouse line (Matn4-mEGFP) and performed single-cell RNA...

Cardiac aging is an intrinsic process that leads to impaired heart function, along with cellular and molecular changes. Recent research highlights the important role of mitochondria in cardiac function, due to the heart's high energy demands. Serum response factor (SRF), a transcription factor involved in regulating actin and smooth muscle gene expression, is well known as a regulator of various aspects of cardiac function. However, its role in mitochondrial regulation and cardiac aging is...

Follow President Donald Trump’s impact on U.S. research and science globally

Opposition to Trump administration and fears of customs run-ins are shifting travel plans

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DOGE argues killing grants saves money, but a Science analysis suggests more than $1.4 billion in sunk research costs may produce few results

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G protein-coupled receptor 3 (GPR3) is a class A orphan receptor characterized by high constitutive activity in the G(s) signaling pathway. GPR3 has been implicated in Alzheimer's disease and the regulation of thermogenesis in human adipocytes, yet the molecular mechanisms underlying its self-activation and potential endogenous modulators remain unclear. In this study, we present cryo-electron microscopy (cryo-EM) structures of GPR3 in different oligomerization states, both in the absence and...

Targeting proteins to their final cellular destination requires transport mechanisms and nearly all lysosomal enzymes reach the lysosome via the mannose-6-phosphate receptor pathway. One of the few known exceptions is the enzyme β-glucocerebrosidase (GCase) that requires the lysosomal integral membrane protein type-2 (LIMP-2) as a proprietary lysosomal transporter. Genetic variations in the GCase encoding gene GBA1 cause Gaucher's disease (GD) and present the highest genetic risk factor to...

Cellular senescence is a stress-inducible state switch relevant in aging, tumorigenesis and cancer therapy. Beyond a lasting arrest, senescent cells are characterized by profound chromatin remodeling and transcriptional reprogramming. We show here myeloid-skewed aberrant lineage plasticity and its immunological ramifications in therapy-induced senescence (TIS) of primary human and murine B-cell lymphoma. We find myeloid transcription factor (TF) networks, specifically AP-1-, C/EBPβ- and...