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3D-generation of high-purity midbrain dopaminergic progenitors and lineage-guided refinement of grafts supports Parkinson's disease cell therapy

3 months ago
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...
Xinyue Zhang

Ribosome dysregulation and intervention in age-related infertility

3 months ago
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...
Jie Li

Exhausted CD8<sup>+</sup> T Cell in HIV Infection Exhibits an Impaired Bioenergetic Metabolism Driven by Mitochondrial Dysfunction

3 months ago
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...
Yee Teng Chan

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

3 months ago
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)...
Gozde Inci

Brain-age models with lower age prediction accuracy have higher sensitivity for disease detection

3 months ago
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,...
Marc-Andre Schulz