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State-specific enhancer landscapes govern microglial plasticity

2 weeks 1 day ago
Single-cell transcriptomic studies have identified distinct microglial subpopulations with shared and divergent gene signatures across development, aging, and disease. Whether these microglial subsets represent ontogenically separate lineages of cells or are manifestations of plastic changes in microglial states downstream of some converging signals is unknown. Furthermore, despite the well-established role of enhancer landscapes underlying the identity of microglia, the extent to which histone...
Nicole Hamagami

Calcium overload induced mitochondrial and lysosomal dysfunction is regulated by Tousled-like kinase in a-synucleinopathy

2 weeks 1 day ago
As a pathological hallmark of Parkinson's disease (PD), a-synucleinopathy induces various cellular damages, including calcium overload, mitochondrial and autophagic dysfunction, ultimately resulting in dopaminergic neuron death. However, the hierarchy of these detrimental events remains unclear. It is well established that a-synuclein can induce calcium overload through diverse mechanisms. To assess whether calcium overload plays a crucial detrimental role, we established a calcium overload...
Fangyan Gong

Targeting C1q signaling in fibro-adipogenic progenitors prevents regenerative fibrosis of aged muscle

2 weeks 1 day ago
Skeletal muscle fibrosis, as occurs with age, in response to injury, or in the setting of degenerative diseases, results in impairments of muscle regeneration and function. Fibro-adipogenic progenitors (FAPs), a distinct population of muscle-resident mesenchymal progenitor cells that reside in the muscle interstitium, play a crucial role in normal muscle regeneration by supporting muscle stem cell proliferation. However, in pathological conditions such as severe or recurrent muscle injury, FAPs...
Abhijnya Kanugovi

Enhanced episodic specificity and socioemotional content in older adults' everyday autobiographical thoughts

2 weeks 1 day ago
Cognitive aging research has long observed that older adults' autobiographical memories and future thoughts, as assessed in laboratory contexts, lack spatiotemporal detail compared to young adults. Does this pattern also hold in everyday contexts? Across two studies, we examined characteristics of autobiographical thinking in real-world settings using ecological momentary assessment (EMA). Study 1 included an adult lifespan sample (N = 3,847). Study 2 (preregistered) included 217 young and older...
Vannia A Puig Rivera

State-specific enhancer landscapes govern microglial plasticity

2 weeks 1 day ago
Single-cell transcriptomic studies have identified distinct microglial subpopulations with shared and divergent gene signatures across development, aging, and disease. Whether these microglial subsets represent ontogenically separate lineages of cells or are manifestations of plastic changes in microglial states downstream of some converging signals is unknown. Furthermore, despite the well-established role of enhancer landscapes underlying the identity of microglia, the extent to which histone...
Nicole Hamagami

Ageing of human myofibres in the Vastus Lateralis muscle: A narrative review

2 weeks 1 day ago
Human skeletal muscle is a complex, dynamic tissue that changes profoundly with age. It comprises heterogenous cells including long, contractile, multinucleated myofibres, broadly classified into type I (slow-twitch/oxidative) fibres and type II (fast-twitch/glycolytic) fibres, as well as a variety of mononucleated cells (e.g., immune, satellite, and endothelial cells), and the extracellular matrix (ECM). Ageing as well as sarcopenia, a muscle condition characterised by progressive loss of...
Antoneta Granic

Platelet aging and desialylation increase apoptotic priming and BCL-X(L) dependence

2 weeks 1 day ago
Platelets are short-lived anucleate cells essential for primary hemostasis and recognized for their functions in thrombosis, immunity, antimicrobial defense, neurodegeneration, as well as cancer growth and metastasis. Their brief lifespan in circulation is controlled by the removal of sialic acid residues from the platelet surface (desialylation) and also the mitochondrial apoptosis pathway, with high expression of the anti-apoptotic protein BCL-X(L) being required for platelet survival. This...
Renata Grozovsky

Taurine transporter SLC6A6 expression promotes mesenchymal stromal cell function

2 weeks 1 day ago
Mesenchymal stromal cell (MSC) differentiation is critical for the development, maintenance, and repair of bone tissue. MSCs also play a key role in regulating self-renewal and differentiation of normal hematopoietic and leukemic stem cells. Our prior work has identified a key role of taurine produced by bone marrow osteolineage cells in supporting the growth of taurine transporter (TauT or Slc6a6) expressing leukemia cells. Here, we analyze multiple murine non-hematopoietic bone marrow...
Christina M Kaszuba

Dynamins maintain nuclear envelope homeostasis and genome stability

2 weeks 1 day ago
The nuclear envelope is a protective barrier for the genome and a mechanotransduction interface between cytoplasm and nucleus, whose malfunction disrupts nucleocytoplasmic transport, compromises DNA repair, accelerates telomere shortening, and promotes genomic instability. Mechanisms governing nuclear envelope remodeling and maintenance in interphase and post-mitotic cells remain poorly understood. Here, we report a role for dynamins, a family of essential brain-enriched membrane- and...
Célia Aveleira