Aggregator
These ‘movies’ of proteins in action are revealing the hidden biology of cells
‘Woah, this is affecting me’: why I’m fighting racial inequality in prostate-cancer research
The warfighter
Number of known moonquakes tripled with discovery in Apollo archive
Within 22,000 new strikes are dozens of mysterious quakes concentrated in the north
Pressure grows to ditch controversial forced swim test in rodent studies of depression
Scientists are searching for more precise ways to gauge the effects of psychiatric drugs on animals
Contrasting somatic mutation patterns in aging human neurons and oligodendrocytes
Characterizing somatic mutations in the brain is important for disentangling the complex mechanisms of aging, yet little is known about mutational patterns in different brain cell types. Here, we performed whole-genome sequencing (WGS) of 86 single oligodendrocytes, 20 mixed glia, and 56 single neurons from neurotypical individuals spanning 0.4-104 years of age and identified >92,000 somatic single-nucleotide variants (sSNVs) and small insertions/deletions (indels). Although both cell types...
HTRA1 disaggregates α-synuclein amyloid fibrils and converts them into non-toxic and seeding incompetent species
Parkinson's disease (PD) is closely linked to α-synuclein (α-syn) misfolding and accumulation in Lewy bodies. The PDZ serine protease HTRA1 degrades fibrillar tau, which is associated with Alzheimer's disease, and inactivating mutations to mitochondrial HTRA2 are implicated in PD. Here, we report that HTRA1 inhibits aggregation of α-syn as well as FUS and TDP-43, which are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The protease domain of HTRA1 is necessary and...
Switch of innate to adaptative immune responses in the brain of patients with Alzheimer's disease correlates with tauopathy progression
Neuroinflammation is a key feature of Alzheimer's disease (AD). In this work, analysis of single- cell RNA-sequencing (scRNA-seq) data obtained from the brain of patients with AD provides evidence supporting a switch from an innate to an adaptative immune response during tauopathy progression, with both disease-associated microglia (DAM) and CD8+ T cells becoming more frequent at advanced Braak stages.
Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment
The potential of immune checkpoint inhibitors (ICI) may be limited in situations where immune cell fitness is impaired. Here, we show that the efficacy of cancer immunotherapies is compromised by the accumulation of senescent cells in mice and in the context of therapy-induced senescence (TIS). Resistance to immunotherapy is associated with a decrease in the accumulation and activation of CD8 T cells within tumors. Elimination of senescent cells restores immune homeostasis within the tumor...
Metabolic regulation of skeletal cell fate and function
Bone development and bone remodelling during adult life are highly anabolic processes requiring an adequate supply of oxygen and nutrients. Bone-forming osteoblasts and bone-resorbing osteoclasts interact closely to preserve bone mass and architecture and are often located close to blood vessels. Chondrocytes within the developing growth plate ensure that bone lengthening occurs before puberty, but these cells function in an avascular environment. With ageing, numerous bone marrow adipocytes...
Stem cell secretome treatment improves whole-body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice
Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral...
‘Jelly in the skull’: Ancient brains are preserved more often than you think
A former undertaker says some thousands-year-old brains could be a valuable scientific resource—and perhaps reveal clues to our past