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7 basic science discoveries that changed the world
Retraction Note: sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance
Epigenetic dysregulation in aged muscle stem cells drives mesenchymal progenitor expansion via IL-6 and Spp1 signaling
Loss of MFE-2 impairs microglial lipid homeostasis and drives neuroinflammation in Alzheimer’s pathogenesis
Aging as a glitch in the matrix
Facing claims of animal abuse, a major breeder of research dogs will close its pipeline
Ridglan Farms has agreed to stop selling beagles for scientific studies, leaving just one major U.S. supplier
Vaccine protects people from paratyphoid fever in a ‘human challenge’ study
Volunteers who swallowed disease-causing bacteria were less likely to get sick after an oral vaccine
Aquarium hijinks provide strongest evidence yet that sharks love to play
Study hints at a deeper intelligence—and a need for enrichment in captivity
Meta and TikTok are obstructing researchers’ access to data, European Commission rules
Data are needed to study how social media spreads misinformation and influences elections, scientists say
To thwart food poisoning, tiny needles could inject bacteria-slaying viruses into your meal
Experimental patches on meat, fruits, and vegetables can destroy up to 99.9% of bacteria
3D-generation of high-purity midbrain dopaminergic progenitors and lineage-guided refinement of grafts supports Parkinson's disease cell therapy
The low in vivo yield of midbrain dopaminergic (mDA) neurons and uncertain lineage fates of donor cells following transplantation impede clinical application of human pluripotent stem cell (hPSC)-based cell therapy for Parkinson's disease (PD). We developed a three-dimensional (3D) differentiation method, SphereDiff, to generate high-purity mDA progenitors (mDAPs), leading to a significant enrichment of mDA neurons post transplantation. Grafted mDA neurons fully restored dopamine levels and...
Ribosome dysregulation and intervention in age-related infertility
Fertility in women decreases with age, but the molecular basis for age-related, unexplained infertility remains elusive. Here, we reveal distinct transcriptome changes in oocytes and surrounding cumulus cells from women in their mid-thirties, as evidenced by notably increased transcription of ribosome genes. Additionally, meiosis genes and actin and cohesin components are downregulated in oocytes with age. Lysosomes and proteostasis are also disrupted in cumulus cells. Moreover, DNA...
Exhausted CD8<sup>+</sup> T Cell in HIV Infection Exhibits an Impaired Bioenergetic Metabolism Driven by Mitochondrial Dysfunction
In people living with HIV (PLWH), persistent viral replication and antiretroviral therapy (ART)-associated toxicity contribute to T cell exhaustion, characterised by significant metabolic reprogramming that negatively impacts cellular function and longevity. Understanding the metabolic dysregulation in exhausted T cells could unveil novel therapeutic strategies to rejuvenate immune responses in PLWH. This study investigated the prevalence and metabolic gene expression profiles of exhausted...
FOXO3a upregulates DNA repair activities by transcriptional activation of target genes and provides the resistance to gamma radiation and the extension of lifespan in mouse
To verify whether DNA repair is regulated by FOXO3a, a tet-on flag-h-FOXO3a transgenic mice were used. RT-q-PCR and western blot analysis showed that the mRNA and protein levels of flag-h-FOXO3a, XRCC4, XPC, APE1 and MSH2 increased dose dependently by doxycycline. DNA repair activities like non-homologous end joining (NHEJ), nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR) also increased in a doxycycline dose dependent manner. MEF (mouse embryonic fibroblast)...
Brain-age models with lower age prediction accuracy have higher sensitivity for disease detection
This study critically reevaluates the utility of brain-age models within the context of detecting neurological and psychiatric disorders, challenging the conventional emphasis on maximizing chronological age prediction accuracy. Our analysis of T1 MRI data from 46,381 UK Biobank participants reveals that simpler machine learning models, and notably those with excessive regularization, demonstrate superior sensitivity to disease-relevant changes compared to their more complex counterparts,...
Telomerase Depletion Accelerates Ageing of the Zebrafish Brain
Decreased telomerase expression, telomere shortening, senescence-associated markers, and inflammation have all been independently observed in the ageing brain and associated with disease. However, causality between limited telomerase expression and brain senescence and neuro-inflammation in the natural ageing setting is yet to be established. Here, we address these questions using the zebrafish as an ageing model. Akin to humans, zebrafish display premature ageing and death in the absence of...
Stage-specific roles of clonally expanded CD8(+) T cells in regulating amyloid pathology in Alzheimer's disease models
Clonally expanded CD8^(+) T cells may contribute to Alzheimer's disease (AD) pathology through interactions with brain-resident cells. However, the functional impact of AD-specific T cell receptor (TCR) clonotypes remains unclear. Here, we demonstrate that CD8^(+) T cells undergo clonal expansion in early-stage AD mouse models, App^(NL-G-F) and 5xFAD, and that their depletion reduces amyloid plaque accumulation. Expanded TCR-expressing CD8^(+) T cells preferentially infiltrate the brain,...
Sex-specific associations of gene expression with Alzheimer's disease neuropathology and ante-mortem cognitive performance
The biological mechanisms underlying the increased prevalence of Alzheimer's disease (AD) in women remain undefined. While previous case/control studies have identified sex-biased molecular pathways, the sex-specific relationships between gene expression and AD endophenotypes, particularly involving sex chromosomes, are underexplored. With bulk transcriptomic data across 3 brain regions from 767 decedents, we investigated sex-specific associations between gene expression and post-mortem...
iPSC-derived ITGA6-positive cells restore aqueous humor outflow in glaucoma eyes
Decreased trabecular meshwork (TM) cellularity is a critical pathogenic cause of primary open-angle glaucoma, yet therapies to regenerate the decellularized TM are very limited. Induced pluripotent stem cell-derived TM-like cells (iPSC-TM) can efficiently restore aqueous humor outflow. Here, we conducted a multi-modal RNA sequencing analysis to characterize the molecular mechanisms underlying TM regeneration. Our clustering analysis identified a group of iPSC-derived alpha6 integrin-positive...
Accelerated growth increases the somatic epimutation rate in trees
Trees are integral to ecosystems and hold considerable economic importance. Their exceptional longevity and modular structure also make them valuable models for studying the long-term accumulation of somatic mutations and epimutations in plants. Empirical evidence indicates that the annual rate of these stochastic events correlates negatively with generation time, suggesting that species with long lifespans have evolved mechanisms to mitigate the build-up of deleterious somatic variants. It has...