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Newly discovered virus is sickening cattle in Western Europe
The pathogen, which reduces milk production, is the latest midge-transmitted virus affecting ruminants to reach the continent
Integrating experimental evolution and transcriptomics reveals the phenotypic and molecular architecture of the pace-of-life syndrome
Phenotypic traits often covary through shared genetic and environmental influences, shaping the evolution of integrated life-history strategies. In particular, correlations between behavioral and life-history traits form the core of the pace-of-life syndrome (POLS) hypothesis, yet direct experimental tests of its evolutionary and molecular foundations remain limited. Here, we combined experimental evolution and transcriptomic analyses to investigate the phenotypic and molecular architecture of...
Beyond the scaffold: Glia as architects of the neural extracellular matrix
Astrocytes, oligodendrocyte lineage cells, and microglia dynamically shape the neural extracellular matrix (ECM) across brain development and aging. Recent findings highlight the potential of glial regulation of the ECM as a framework for understanding circuit formation and identify previously unrecognized targets in neurological diseases.
Human PMS1-dependent non-canonical mismatch repair engages with MBD4 to repair methylated CpG deamination
CpG dinucleotides are mutational hotspots due to spontaneous deamination of 5-methylcytosine (5mC), resulting in T:G mismatches that can lead to CpG>TpG transitions. These mutations are a hallmark of aging and cancer and play a central role in the evolution of vertebrate genomes. We have previously uncovered MBD4 as the primary base excision repair (BER) glycosylase responsible for 5mC deamination repair. Here, we employ an APOBEC1 deaminase fused to a catalytically dead Cas9 to induce targeted...
Inhibiting Ribosomal RNA Synthesis in C. elegans Protects Against Reductive Stress During de novo Fatty Acid Synthesis Deficiency
Reductive stress has remained underappreciated as a significant disrupter of redox homeostasis. Recent studies have begun to link the accumulation of NADH and NADPH to the development and progression of metabolic diseases such as cancer, cardiac disease, and diabetes. In this study we use the nematode Caenorhabditis elegans to examine the phenomenon of catastrophic reductive-death caused by combined biguanide treatment and fasn-1 deficiency. This process of synergistic biguanide-induced...
In vivo mapping of striatal neurodegeneration in Huntington's disease with Soma and Neurite Density Imaging
Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by progressive cognitive and motor decline driven by basal ganglia (BG) atrophy. Clinical trials of novel disease-modifying therapies are ongoing, creating a need for sensitive non-invasive imaging biomarkers. Soma and Neurite Density Imaging (SANDI) is a multi-shell diffusion MRI model that estimates intracellular signal fractions from sphere-shaped soma and shows promise as a marker of neurodegeneration. The...
Amenable Mortality Among Older Brazilians: Evidence From the Brazilian Longitudinal Study of Aging (ELSI-Brazil)
BackgroundAmenable mortality, deaths preventable through timely and effective healthcare, is a widely used indicator of health system performance, yet evidence is lacking on its individual-level determinants in Brazil.MethodsWe used data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a representative cohort of adults aged 50 and older. Deaths were classified as amenable using both the Brazilian and the Pan American Health Organization's definitions. Semi-parametric competing risks...