Aggregator

New dates for a throwing weapon found in Poland reveal it as one of the earliest of its kind

Students in the life sciences are shut out of latest cohort of 500 fellows

White House battle with Ivy League school disrupts databases and networks relied on by other universities

After a judge told agency to restore hundreds of killed grants, NIH backs off plans to cancel more existing projects

The Christchurch mutation (R136S) in the APOE3 (E3S/S) gene is associated with attenuated tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high amyloid burden in the carrier. However, the molecular mechanisms enabling the E3S/S mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse Apoe with wild-type human APOE3 or APOE3S/S on a tauopathy background. The R136S mutation decreased tau load and protected against tau-induced...

Neurodegenerative diseases activate innate and adaptive immune responses that can either slow or accelerate disease progression. Here, we sought to define beneficial immune pressures that emerge during tauopathy development in mice and humans. Using mice that express mutant human tau in neurons, we observed that microglia slowed tauopathy development by controlling the spread of phosphorylated tau (pTau) in the central nervous system and blood. However, over time microglia converted into...

No abstract

Clinical care for patients with limited life expectancy often requires adjustments, prioritizing immediate benefits over long-term outcomes, as the relevance of future complications diminishes. This study identifies indicators of mortality risk in horses with chronic orthopaedic conditions to enhance individualized care and welfare. Over 3 years, 123 chronically lame horses and 6 healthy control horses at an animal sanctuary underwent regular (every 3 months) comprehensive health assessments and...

CONCLUSION: This study found a significant association between frailty and multiple factors, particularly oral function. Specifically, diminished swallowing function has emerged as a notable independent predictor of frailty progression.

Alzheimer's disease (AD) is a neurocognitive disorder that affects a significant part of the population. Its symptoms include progressive loss of memory and executive dysfunction. Genetic susceptibility to AD can be influenced by allele variants of the APOE gene. On the other hand, lifelong experiences such as educational attainment, occupational complexity, and leisure activities, known proxies for cognitive reserve (CR), may modulate gene expression, ultimately impacting AD susceptibility. In...

The decline of adult neurogenesis and neuronal function during aging underlies the onset and progression of neurodegenerative diseases such as Alzheimer's disease. Conventional therapies, including neurotransmitter modulators and antibodies targeting pathogenic proteins, offer only symptomatic improvement. As the most abundant glial cells in the brain, astrocytes outnumber neurons nearly fivefold. However, their proliferative and transdifferentiation potential renders them ideal candidates for...

Alzheimer's disease (AD) is the main cause of dementia in the old-age population worldwide. AD is a progressive brain neurodegenerative disease due to genetic and environmental factors that induce the accumulation of intracellular hyperphosphorylated tau protein and extracellular amyloid protein (Aβ). Particularly, cholinergic neurons in the prefrontal cortex and hippocampus are mainly affected in AD, resulting in cognitive impairment and memory dysfunction. Therefore, restoration of cholinergic...

Changes in the transcriptome are critical in shaping the structural plasticity of neurons, which underpins learning and long-term memory storage. Here, we explored the effect of two opposing, plasticity-associated pathways-cAMP second-messenger signaling and metabotropic glutamate receptor (mGluR1 and mGluR5) signaling-on the transcriptome in hippocampal neurons and how these pathways operate in distinct and coordinated manners to induce structural changes. Integration of transcriptome data and...

Cannabinoid receptor type-1 (Cnr1) signalling declines with age, which may contribute to the ageing process, as Cnr1 activity influences several hallmarks of ageing. Indeed, previous studies have shown that mice with a genetic deletion of Cnr1 (Cnr1^(-/-)) exhibit an early onset of brain ageing. However, it is not yet clear whether Cnr1 activity influences life span and the pace of bodily ageing. Thus, we asked whether the life- and health-span of Cnr1^(-/-) mice differs from their wild-type...

Alzheimer's disease (AD) is a neurocognitive disorder that affects a significant part of the population. Its symptoms include progressive loss of memory and executive dysfunction. Genetic susceptibility to AD can be influenced by allele variants of the APOE gene. On the other hand, lifelong experiences such as educational attainment, occupational complexity, and leisure activities, known proxies for cognitive reserve (CR), may modulate gene expression, ultimately impacting AD susceptibility. In...

The decline of adult neurogenesis and neuronal function during aging underlies the onset and progression of neurodegenerative diseases such as Alzheimer's disease. Conventional therapies, including neurotransmitter modulators and antibodies targeting pathogenic proteins, offer only symptomatic improvement. As the most abundant glial cells in the brain, astrocytes outnumber neurons nearly fivefold. However, their proliferative and transdifferentiation potential renders them ideal candidates for...

Mutations in the mitochondrial genome can cause maternally inherited diseases, cancer, and aging-related conditions. Recent technological progress now enables the creation and correction of mutations in the mitochondrial genome, but it remains relatively unknown how patients with primary mitochondrial disease can benefit from this technology. Here, we demonstrate the potential of the double-stranded DNA deaminase toxin A-derived cytosine base editor (DdCBE) to develop disease models and...

Reproductive aging is associated with declining fertility and increasing inflammation, though these events are not well understood. An exciting new study in PLOS Biology utilizes cutting-edge technologies to characterize the role of multinucleated giant cells in ovarian aging.

Striatal cholinergic interneurons (SCINs) exhibit pause responses conveying information about rewarding events, but the mechanisms underlying these pauses remain elusive. Thalamic inputs induce a pause mediated by intrinsic mechanisms and regulated by dopamine D2 receptors (D2Rs), though the underlying membrane currents remain unknown. Moreover, the role of D5 receptors (D5Rs) has not been addressed so far. Here, we performed ex vivo studies showing that glutamate released by thalamic inputs in...

BACKGROUND: Epidemiological data of populations living at moderate altitudes between 1,000 and 2,000 m suggest healthier aging when compared to people living in lower regions. Besides social determinants of health, lifestyle and cardiovascular risk factors, environmental conditions such as ambient temperature, air pollution and aeroallergens, solar radiation and in particular hypobaric hypoxia may modify the risk of disease development and mortality. The present study was aimed at (1) evaluating...