Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment.

Introduction: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention.

Methods: Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry.

Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19.

Components that comprise our brain parenchymal and cerebrovascular structures provide a homeostatic environment for proper neuronal function to ensure normal cognition. Cerebral insults (e.g.

Loss of Direct Vascular Contact to Astrocytes in the Hippocampus as an Initial Event in Alzheimer's Disease. Evidence from Patients, In Vivo and In Vitro Experimental Models.

Alzheimer's disease (AD) is characterized by the accumulation of aggregated amyloid peptides in the brain parenchyma and within the walls of cerebral vessels. The hippocampus-a complex brain structure with a pivotal role in learning and memory-is implicated in this disease. However, there is limited data on vascular changes during AD pathological degeneration in this susceptible structure, which has distinctive vascular traits.

Vascular mechanisms leading to progression of mild cognitive impairment to dementia after COVID-19: Protocol and methodology of a prospective longitudinal observational study.

Introduction: Mild cognitive impairment (MCI) is a prodromal stage to dementia, affecting up to 20% of the aging population worldwide. Patients with MCI have an annual conversion rate to dementia of 15-20%. Thus, conditions that increase the conversion from MCI to dementia are of the utmost public health concern.

Mitochondrial calcium uniporter deficiency in dentate granule cells remodels neuronal metabolism and impairs reversal learning.

The mitochondrial calcium uniporter (MCU) is the main route of calcium (Ca) entry into neuronal mitochondria. This channel has been linked to mitochondrial Ca overload and cell death under neurotoxic conditions, but its physiologic roles for normal brain function remain poorly understood. Despite high expression of MCU in excitatory hippocampal neurons, it is unknown whether this channel is required for learning and memory.

Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy.

Vascular mechanisms of Alzheimer's disease (AD) may constitute a therapeutically addressable biological pathway underlying dementia. We previously demonstrated that soluble pathogenic forms of tau (tau oligomers) accumulate in brain microvasculature of AD and other tauopathies, including prominently in microvascular endothelial cells. Here we show that soluble pathogenic tau accumulates in brain microvascular endothelial cells of P301S(PS19) mice modeling tauopathy and drives AD-like brain microvascular deficits.

Rapamycin restores peripheral blood flow in aged mice and in mouse models of atherosclerosis and Alzheimer's disease.

Peripheral artery disease (PAD), defined as reduced blood flow to the lower limbs, is a serious disorder that can lead to loss of function in the lower extremities and even loss of limbs. One of the main risk factors for PAD is age, with up to 25% of adults over the age of 55 and up to 40% over the age of 80 presenting with some form of the disease. While age is the largest risk factor for PAD, other risk factors include atherosclerosis, smoking, hypertension, and diabetes.

Effect of Nrf2 loss on senescence and cognition of tau-based P301S mice.

Cellular senescence may contribute to chronic inflammation involved in the progression of age-related diseases such as Alzheimer's disease (AD), and its removal prevents cognitive impairment in a model of tauopathy. Nrf2, the major transcription factor for damage response pathways and regulators of inflammation, declines with age. Our previous work showed that silencing Nrf2 gives rise to premature senescence in cells and mice.

Henipaviruses: an expanding global public health concern?

Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic zoonotic viruses of the genus Henipavirus, family Paramyxoviridae that cause severe disease outbreaks in humans and also can infect and cause lethal disease across a broad range of mammalian species. Another related Henipavirus has been very recently identified in China in febrile patients with pneumonia, the Langya virus (LayV) of probable animal origin in shrews. NiV and HeV were first identified as the causative agents of severe respiratory and encephalitic disease in the 1990s across Australia and Southern Asia with mortality rates reaching up to 90%.

Monkeypox: considerations for the understanding and containment of the current outbreak in non-endemic countries.

The neglected and rare zoonotic disease caused by monkeypox virus (MPV) has recently spread widely, resulting in the largest known monkeypox outbreak outside of Africa, where it is endemic. MPV belongs to the Poxviridae family, genus Orthopoxvirus. At least two different clades have been identified, each having different fatality rates but recent cases are all phylogenetically related to the West African clade.

Genetic and pharmacologic proteasome augmentation ameliorates Alzheimer's-like pathology in mouse and fly APP overexpression models.

The proteasome has key roles in neuronal proteostasis, including the removal of misfolded and oxidized proteins, presynaptic protein turnover, and synaptic efficacy and plasticity. Proteasome dysfunction is a prominent feature of Alzheimer's disease (AD). We show that prevention of proteasome dysfunction by genetic manipulation delays mortality, cell death, and cognitive deficits in fly and cell culture AD models.

Brain cellular senescence in mouse models of Alzheimer's disease.

The accumulation of senescent cells contributes to aging pathologies, including neurodegenerative diseases, and its selective removal improves physiological and cognitive function in wild-type mice as well as in Alzheimer's disease (AD) models. AD models recapitulate some, but not all components of disease and do so at different rates. Whether brain cellular senescence is recapitulated in some or all AD models and whether the emergence of cellular senescence in AD mouse models occurs before or after the expected onset of AD-like cognitive deficits in these models are not yet known.

Editorial: Comparison of antibody and T cell responses elicited by BBIBP-CorV (Sinopharm) and BNT162b2 (Pfizer-BioNTech) vaccines against SARS-CoV-2 in healthy adult humans.

Vaccine development has become the main tool for reducing COVID-19 cases and the severity of the disease. Comparative analyses of adaptive immunity generated by different vaccines platforms are urgently needed. Multiple studies have compared different vaccines using similar platforms; however, comparative analyses of vaccines across different platforms are lacking.

Evolution of the Use of Corticosteroids for the Treatment of Hospitalised COVID-19 Patients in Spain between March and November 2020: SEMI-COVID National Registry.

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations.

Material And Methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID-19 Registry from March to November 2020.

Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer's disease-like neuroinflammation and cognitive impairment.

Background: Human genetic association studies point to immune response and lipid metabolism, in addition to amyloid-beta (Aβ) and tau, as major pathways in Alzheimer's disease (AD) etiology. Accumulating evidence suggests that chronic neuroinflammation, mainly mediated by microglia and astrocytes, plays a causative role in neurodegeneration in AD. Our group and others have reported early and dramatic losses of brain sulfatide in AD cases and animal models that are mediated by ApoE in an isoform-dependent manner and accelerated by Aβ accumulation.

San Antonio Nathan Shock Center: your one-stop shop for aging research.

With evolving cores, enrichment and training programs, and supported research projects, the San Antonio (SA) Nathan Shock Center has for 26 years provided critical support to investigators locally, nationally, and abroad. With its existing and growing intellectual capital, the SA Nathan Shock Center provides to local and external investigators an enhanced platform to conduct horizontally integrated (lifespan, healthspan, pathology, pharmacology) transformative research in the biology of aging, and serves as a springboard for advanced educational and training activities in aging research. The SA Nathan Shock Center consists of six cores: Administrative/Program Enrichment Core, Research Development Core, Aging Animal Models and Longevity Assessment Core, Pathology Core, Analytical Pharmacology and Drug Evaluation Core, and Integrated Physiology of Aging Core.

mTOR Attenuation with Rapamycin Reverses Neurovascular Uncoupling and Memory Deficits in Mice Modeling Alzheimer's Disease.

Vascular dysfunction is a universal feature of aging and decreased cerebral blood flow has been identified as an early event in the pathogenesis of Alzheimer's disease (AD). Cerebrovascular dysfunction in AD includes deficits in neurovascular coupling (NVC), a mechanism that ensures rapid delivery of energy substrates to active neurons through the blood supply. The mechanisms underlying NVC impairment in AD, however, are not well understood.

Conservation actions and ecological context: optimizing coral reef local management in the Dominican Republic.

Over the past few decades, coral reef ecosystems have been lost at accelerated rates as a result of global climate change and local stressors. Local management schemes can help improve the condition of coral reefs by enhancing their ecosystem recovery capacity. Caribbean conservation efforts include mitigation of local anthropogenic stressors, and integrating social participation.

Primary neuron and astrocyte cultures from postnatal Callithrix jacchus: a non-human primate in vitro model for research in neuroscience, nervous system aging, and neurological diseases of aging.

The ability to generate in vitro cultures of neuronal cells has been instrumental in advancing our understanding of the nervous system. Rodent models have been the principal source of brain cells used in primary cultures for over a century, providing insights that are widely applicable to human diseases. However, therapeutic agents that showed benefit in rodent models, particularly those pertaining to aging and age-associated dementias, have frequently failed in clinical trials.

Modification of PapA5 acyltransferase substrate selectivity for optimization of short-chain alcohol-derived multimethyl-branched ester production in Escherichia coli.

Plant waxes are interesting substitutes of fossil-derived compounds; however, their limited sources and narrow structural diversity prompted the development of microbial platforms to produce esters with novel chemical structures and properties. One successful strategy was the heterologous expression of the mycocerosic polyketide synthase-based biosynthetic pathway (MAS-PKS, PapA5 and FadD28 enzymes) from Mycobacterium tuberculosis in Escherichia coli. This recombinant strain has the ability to produce a broad spectrum of multimethyl-branched long-chain esters (MBE) with novel chemical structures and high oxidation stability.