Emergency granulopoiesis, or the de novo generation of neutrophils in response to a systemic infection through proliferation of myeloid progenitor cells, is an important fundamental host response to severe infections. The authors demonstrate that bone marrow mesenchymal stromal cells, known to support the hematopoietic niche, secrete paracrine factors that can augment emergency granulopoiesis.
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The authors show that antibody responses to the receptor binding domain of the spike protein of SARS-CoV-2 persist beyond 3-4 months of infection, and these responses are highly correlated with the presence of neutralizing antibodies. They also found that measuring different types of antibodies may be helpful. Knowing this information can help scientists better interpret antibody results and get more accurate data about the spread of COVID-19.
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In many biomaterial systems, plastic deformation of extracellular matrix, degradation, or relaxation of stress are coupled and therefore their effects on cell phenotype are difficult to isolate. Using a polymer plasticizing architecture that specifically decouples irreversible creep from stress relaxation and modulus, network plasticity is shown to have a biphasic relationship with cell spreading.
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A hexanucleotide repeat expansion at C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Initial studies of bacterial artificial chromosome (BAC) transgenic mice harboring this expansion described an absence of motor and survival phenotypes. However, a recent study by Liu and colleagues described transgenic mice harboring a large repeat expansion (C9-500) and reported decreased survival…
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Early developmental specification can be modeled by differentiating embryonic stem cells (ESCs) to embryoid bodies (EBs), a heterogeneous mixture of three germ layers. Here, we combine single-cell transcriptomics and genetic recording to characterize EB differentiation. We map transcriptional states along a time course and model cell fate trajectories and branchpoints as cells progress to distinct germ layers. To validate this…
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The α-synuclein protein accumulates in Parkinson’s disease and other synucleinopathies. Growing evidence suggests that lipid-rich vesicle clusters containing α-synuclein form the basis of the neuropathological Lewy bodies. The authors describe benefits when treating with inhibitors of the enzyme stearoyl-CoA desaturase in two α-synuclein mouse models.
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This study observed that caffeine and its related analytes were lower in individuals with Parkinson's disease's (PD) than in controls, with a greater difference seen when comparing LRRK2 mutation carriers with PD against carriers without the disease. This finding in LRRK2 mutation carriers suggests that caffeine or its analytes could be a potential marker of resistance to developing PD in these individuals.
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Targeting the HIF2–VEGF Axis in Renal Cell Carcinoma

Insights into the role of the tumor suppressor pVHL in oxygen sensing motivated the testing of drugs that target the transcription factor HIF or HIF-responsive growth factors, such as VEGF, for the treatment of cancers caused by VHL inactivation, such as clear-cell renal cell carcinoma (ccRCC). Multiple VEGF inhibitors are now approved for the treatment of ccRCC, and a HIF2α inhibitor has…
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Loss of PTEN, the negative regulator of PI3K activity, is frequent in glioblastomas (GBMs). However, the role of the two major PI3K isoforms, p110α and p110β, in PTEN-deficient gliomagenesis remains unknown. We show that PTEN-deficient GBM largely depends on p110α for proliferation and p110β for migration. Genetic ablation of either isoform delays tumor progression in mice, but only ablating both…
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The authors discovered that exercising muscle selectively releases the mitochondrial metabolite succinate. Once released, succinate co-ordinates paracrine signaling through ligation of its cognate GPCR SUCNR1, which is expressed in a variety of non-myofibrillar cells resident in muscle tissue. This newfound succinate secretion pathway is critical for physiological adaptations to exercise in mice, including remodeling of muscle innervation, muscle ECM, and improvements in muscle strength.
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