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Reimagining human-centric drug development with new approach methodologies
Science, Volume 392, Issue 6796, Page 371-378, April 2026.
Grand canyon’s origin resolved? Ancient lake's flood may have etched famed gorge
Mineral grains show Colorado River filled a basin at the canyon’s head millions of years ago
Scientists stunned by ‘fundamentally new way’ life produces DNA
Newly discovered bacterial defense system challenges genetic code’s central dogma
First complete genome loaded onto a quantum computer
Researchers encode the tiny hepatitis D virus in an early step toward “quantum genomics”
Ten thousand years ago, human evolution went into overdrive
Ancient DNA reveals “massive” genetic shifts tied to rise of farming, wheels, and metal tools
Electromagnetic field-inducible in vivo gene switch for remote spatiotemporal control of gene expression
Gaining precise control of gene expression is crucial in biomedical applications. However, spatiotemporal precision remains challenging. Here, we present a remotely controlled in vivo gene switch responsive to electromagnetic fields (EMFs) that enables precise spatiotemporal activation of target genes. We uncovered the EMF-inducible gene switch activation mechanism via a CRISPR-Cas9 screen, identifying cytochrome b5 type B (Cyb5b) as an essential mediator likely acting as an EMF sensor. The...
Single-nucleus brain transcriptomics reveals microglia dysfunction in multiple system atrophy
Multiple system atrophy (MSA) is a rare, age-related neurodegenerative disease that shares clinical and pathological features with Parkinson's disease (PD) but presents a more devastating disease course. To elucidate the distinct cellular pathophysiology, we performed single-nucleus RNA sequencing on postmortem striatal brain tissue from 7 MSA and 12 PD patients, and 10 non-neurological cases. Here, we show significant compositional differences in astroglia and microglia subtypes, while...
Variants in the proteasome regulator PSMF1 cause a phenotypic spectrum from parkinsonism to perinatal lethality
Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here we identify PSMF1 as a gene implicated in parkinsonism and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD to perinatal...
Human immune aging clock identifies RUNX1 as a decelerator of T cell senescence
Immunosenescence drives organismal aging, yet quantifying its heterogeneity to uncover therapeutic targets remains challenging. We construct a human immune aging clock from single-cell multi-omics data of nearly 1.2 million human peripheral blood mononuclear cells from 230 individuals, precisely mapping immune aging. T cell (TC) transcriptomes are key predictors, revealing hallmarks such as naive cell loss and clonal contraction. This framework identifies the transcription factor RUNX1, whose...
Cellular memory of sub-lethal stress
Regulated cell death-processes such as apoptosis, pyroptosis, necroptosis, and ferroptosis-is essential for development, tissue homeostasis, and response to infection or cellular stress. The proteins involved in regulated cell death necessarily possess powerful and potentially damaging activities, including proteolysis, membrane pore formation, DNA cleavage, and inflammatory pathway activation. Traditionally, these activities drive cell death. However, sub-lethal activation of these pathways...
Plasma cell ontogenies, functions, and lifespans
B cell development is one of the best-understood processes within the immune system. Coordination between transcriptional programs and antigen receptor assembly determines B cell fate, diversifies the antibody repertoire, and allocates specificities to the best-suited subsets. This enables B cells to respond to a wide variety of challenges, which, when encountered, can lead B cells to seemingly converge upon a common fate: the antibody-secreting plasma cell. Yet, as we discuss in this review,...
Electromagnetic field-inducible in vivo gene switch for remote spatiotemporal control of gene expression
Gaining precise control of gene expression is crucial in biomedical applications. However, spatiotemporal precision remains challenging. Here, we present a remotely controlled in vivo gene switch responsive to electromagnetic fields (EMFs) that enables precise spatiotemporal activation of target genes. We uncovered the EMF-inducible gene switch activation mechanism via a CRISPR-Cas9 screen, identifying cytochrome b5 type B (Cyb5b) as an essential mediator likely acting as an EMF sensor. The...
Mapping the landscape of Hutchinson-Gilford Progeria Syndrome research: A bibliometric analysis (1995-2025)
CONCLUSION: This bibliometric survey defines the age and focus of the research into HGPS, with published research being highly concentrated and collaborative and showing possible future research directions in regenerative therapy and epigenetic control. Although the modern knowledge about the progeria condition has grown significantly, there is still a significant drawback of the psychosocial research, prolonged therapy trials, and equity in research participation globally. The results thus...
The impact of HIIT and plasma injection on skeletal muscle morphology in aged rats: Insights into age-related muscle remodeling
CONCLUSION: HIIT and plasma from young trained rats may offer protective or restorative benefits against sarcopenia. These findings highlight the therapeutic potential of combining or alternating exercise and plasma-based strategies in elderly populations.
Age-dependent mutational loads in human tRNA genes are tumor-specific and result in chimeric tRNA sequences that could disrupt the genetic code
Transfer RNA genes (tDNAs) are essential genomic elements that safeguard translational fidelity. Using the T2T version of the human genome we have mapped the position of human tDNAs and analyzed their individual transcriptional activities. Then we have characterized, at single base resolution, the impact of somatic mutations in human tDNAs and its relationship to the transcriptional status of each gene. We confirm that tDNAs are hotspots for somatic mutagenesis, and show that they display...
Dipolar interaction-mediated molecular anchoring electrolyte enables wide-temperature sodium-ion batteries with enhanced safety and durability
Given intractable challenges faced by practical sodium-ion batteries in safety, lifespan and broad temperature adaptability with synergistic interfacial compatibility, persistent efforts in electrolyte engineering are imperative to expedite their commercialization. Here we design a molecular anchoring electrolyte with flame retardancy, oxidative/reductive reliability and electrochemical durability against various electrodes. Through multiple dipolar interactions (δ^(+)H-δ^(-)F and...
Cellular retinoic acid-binding protein 1, CRABP1, in thyroid gland aging
Aging differentially affects disease risks of various organs¹. The endocrine organs undergo significant changes along aging. Clinical reports showed increased prevalence of thyroid disorders with age, especially hypothyroidism². Primary hypothyroidism includes congenital, autoimmune, and iatrogenic causes, which can occur throughout the lifespan. But those with unknown aetiology increase dramatically (~5 fold) in the elderly (≥75 years old)^(3,4). In thyrocytes, accumulated thyroglobulin...
Chromatin remodeling during brain aging
No abstract
Amyloid-beta-driven glymphatic dysfunction in Alzheimer's disease model mice is driven by Ca(2+)-mediated increases in astrocytic cholesterol
Disruptions in the glymphatic system and its downstream meningeal lymphatic drainage pathway, crucial for brain waste clearance, are linked to the pathogenesis of Alzheimer's disease (AD), yet the underlying mechanisms remain unclear. Abnormal calcium dynamics in astrocytes represents an early event in the mouse models of AD. Here we show functional association between amyloid-β-induced elevation of Ca^(2+) dynamics in medial prefrontal cortex astrocytes and glymphatic dysfunction in cognitively...
An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration
Biomarkers to determine underlying frontotemporal lobar degeneration (FTLD) tau or TAR DNA-binding protein (TDP) pathology during life are needed to advance clinical trials targeting specific FTD pathologies. For this purpose, we developed a new ultrasensitive immunoassay to quantify acetylated tau at lysine 174 (AcTau174) in cerebrospinal fluid (CSF). In a sporadic cohort (n = 513), AcTau174 concentrations were higher in all dementia groups (FTLD-TDP, FTLD-Tau, Alzheimer's disease (AD), mild...