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Aging-associated vulnerability to coronavirus disease 2019 (COVID-19) remains poorly understood. Here, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected aged mice lacking SIRT2, a cytosolic NAD^(+)-dependent deacetylase, develop more severe disease and show increased mortality, while treatment with an NAD^(+) booster, 78c, protects aged mice from lethal infection. Mechanistically, we demonstrate that SIRT2 modulates the acetylation of cyclic GMP-AMP synthase...

An overlooked “gate” governs nutrient transport to seeds and might one day boost harvests

New governing coalition also plans to woo scientists from abroad and make it easier for universities to collaborate with the military on defense research

White House aims to end NOAA’s research office; NASA also targeted

Study suggests microplastics have been affecting freshwater animal communities for decades

α-synuclein transmission and propagation are hallmarks of synucleinopathies, yet the molecular mechanisms remain elusive. Using α-synuclein preformed fibrils as pathological seeds, we observed a gradual decline in neuronal transmission activity during serial propagation. Fibril polymorphisms were identified from the initial generation: mini-P, with higher neuronal seeding activity, and mini-S, which accelerated recombinant α-synuclein aggregation. Changes in their proportions during propagation...

Alzheimer's disease (AD) is a growing neurological disorder giving impact cognition and memory, posing a global health challenge with over 55 million individuals affected. It is the 7th foremost cause of dying worldwide, and its pervasiveness is expected to twofold in each five years, reaching 115 million by 2050. AD is characterized by neurofibrillary tangles, senile plaques, and oxidative stress, leading to synaptic failure and cognitive decline. Currently, there is no cure, and available...

Early, efficient Parkinson's disease (PD) tests may facilitate pre-symptomatic diagnosis and disease-modifying therapies. Here we report elevated levels of PD-specific transfer RNA fragments carrying a conserved sequence motif (RGTTCRA-tRFs) in the substantia nigra, cerebrospinal fluid and blood of patients with PD. A whole blood qPCR test detecting elevated RGTTCRA-tRFs and reduced mitochondrial-originated tRFs (MT-tRFs) segregated pre-symptomatic patients with PD from controls (area under the...

Despite recent progress in cancer treatment, liver metastases persist as an unmet clinical need. Here, we show that arming liver and tumor-associated macrophages in vivo to co-express tumor antigens (TAs), IFNα, and IL-12 unleashes robust anti-tumor immune responses, leading to the regression of liver metastases. Mechanistically, in vivo armed macrophages expand tumor reactive CD8^(+) T cells, which acquire features of progenitor exhausted T cells and kill cancer cells independently of CD4^(+) T...

CD8^(+) T cells that are repeatedly exposed to antigenic stimulation, such as in the context of progressing neoplasms and chronic viral infections, acquire a dysfunctional or hypofunctional state that is generally known as exhaustion. There have been considerable efforts to develop therapeutic strategies that prevent exhaustion in these pathological scenarios, but there has been limited success. This may be because exhaustion is not the only source of T cell hypofunction in cancer and chronic...

Fibroblasts form a major component of the stroma in normal mammary tissue and breast tumors. Here, we have applied longitudinal single-cell transcriptome profiling of >45,000 fibroblasts in the mouse mammary gland across five different developmental stages and during oncogenesis. In the normal gland, diverse stromal populations were resolved, including lobular-like fibroblasts, committed preadipocytes and adipogenesis-regulatory, as well as cycling fibroblasts in puberty and pregnancy. These...

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Sex disparities have been epidemiologically demonstrated in non-reproductive cancers, yet how the sex-specific intrinsic microbiome orchestrates the immune system to affect these disparities is unclear. Here we identify a subpopulation of RETNLG^(+)LCN2^(+) senescence-like neutrophils (RLSNs) that preferentially accumulate in the male tumor microenvironment and exert a strong immunosuppressive effect to limit antitumor immunity, resulting in poor prognosis for patients with bladder cancer. This...

Clinical and genetic research links altered cholesterol metabolism with ALS development and progression, yet pinpointing specific pathomechanisms remain challenging. We investigated how cholesterol dysmetabolism interacts with protein aggregation, demyelination, and neuronal loss in ALS. Bulk RNAseq transcriptomics showed decreased cholesterol biosynthesis and increased cholesterol export in ALS mouse models (GA-Nes, GA-Camk2a GA-CFP, rNLS8) and patient samples (spinal cord), suggesting an...

Differentiating sequencing errors from true variants is a central genomics challenge, calling for error suppression strategies that balance costs and sensitivity. For example, circulating cell-free DNA (ccfDNA) sequencing for cancer monitoring is limited by sparsity of circulating tumor DNA, abundance of genomic material in samples and preanalytical error rates. Whole-genome sequencing (WGS) can overcome the low abundance of ccfDNA by integrating signals across the mutation landscape, but higher...

CONCLUSION: The core category,'Seniors on the margin of digital health literacy,'was selected to encompass the other seven categories.

CONCLUSION: This study identified the primary facilitators and barriers to community-based cognitive impairment management within the context of current policies. To enhance the effectiveness of interventions, policymakers, health departments, and community organizations should actively address the identified barriers and leverage the facilitators. Additionally, the findings provide valuable insights for other countries facing similar challenges in cognitive impairment management. Future...

RNA editing is a posttranscriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte-specific, ADAR1-mediated RNA editing in neuroinflammation in Parkinson's disease (PD). We generated human induced pluripotent stem cell-derived astrocytes, neurons and cocultures and exposed them to small soluble alpha-synuclein aggregates. Oligomeric alpha-synuclein triggered an inflammatory glial state associated with Toll-like receptor...

Neurodegenerative disorders such as Alzheimer's disease and macular degeneration represent major sources of human suffering, yet factors influencing disease severity remain poorly understood. Sex has been implicated as one modifying factor. Here, we show that female sex is a risk factor for worsened outcomes in a model of retinal degeneration and that this susceptibility is caused by the presence of female-specific sex hormones. The adverse effect of female sex hormones was specific to diseased...

In Arabidopsis, late endosome-localized ABNORMAL SHOOT 3 (ABS3) promotes senescence through a direct interaction with AUTOPHAGY8 (ATG8). However, the molecular mechanisms underlying the regulation of the ABS3-mediated senescence pathway are not well understood. Here, we report that HOOKLESS 1 (HLS1) acts as a negative regulator of plant senescence and the ABS3-mediated senescence pathway. We identify the localizations of HLS1 at the plasma membrane and endosomes in addition to the nucleus....