Biological sex matters in brain aging.

Every cell in the body has a biological sex. The expansion of aging research to investigate female- and male-specific biology heralds a major advance for human health. Unraveling and harnessing mechanistic etiologies of sex differences may reveal new diagnostics and therapeutics for the aging brain.

Endogenous mitochondrial NAD(P)H fluorescence can predict lifespan.

Many aging clocks have recently been developed to predict health outcomes and deconvolve heterogeneity in aging. However, existing clocks are limited by technical constraints, such as low spatial resolution, long processing time, sample destruction, and a bias towards specific aging phenotypes. Therefore, here we present a non-destructive, label-free and subcellular resolution approach for quantifying aging through optically resolving age-dependent changes to the biophysical properties of NAD(P)H in mitochondria through fluorescence lifetime imaging (FLIM) of endogenous NAD(P)H fluorescence.

Multi-ancestry GWAS reveals loci linked to human variation in LINE-1- and Alu-copy numbers.

Long INterspersed Element-1 (LINE-1; L1) and Alu are two families of transposable elements (TEs) occupying ~17% and ~11% of the human genome, respectively. Though only a small fraction of L1 copies is able to produce the machinery to mobilize autonomously, Alu elements and degenerate L1 copies can hijack their functional machinery and mobilize . The expression and subsequent copy number expansion of L1 and Alu can exert pathological effects on their hosts, promoting genome instability, inflammation, and cell cycle alterations.

Dynamics of microRNA secreted via extracellular vesicles during the maturation of embryonic stem cell-derived retinal pigment epithelium.

Retinal pigment epithelial (RPE) cells are exclusive to the retina, critically multifunctional in maintaining the visual functions and health of photoreceptors and the retina. Despite their vital functions throughout lifetime, RPE cells lack regenerative capacity, rendering them vulnerable which can lead to degenerative retinal diseases. With advancements in stem cell technology enabling the differentiation of functional cells from pluripotent stem cells and leveraging the robust autocrine and paracrine functions of RPE cells, extracellular vesicles (EVs) secreted by RPE cells hold significant therapeutic potential in supplementing RPE cell activity.

Lower entorhinal cortex thickness is associated with greater financial exploitation vulnerability in cognitively unimpaired older adults.

Research suggests that increased financial exploitation vulnerability due to declining decision making may be an early behavioral manifestation of brain changes occurring in preclinical Alzheimer's disease. One of the earliest documented brain changes during the preclinical phase is neurodegeneration in the entorhinal cortex. The objective of the current study was to examine the association between a measure of financial exploitation vulnerability and thickness in the entorhinal cortex in 97 cognitively unimpaired older adults.

The evolution of computational research in a data-centric world.

Computational data-centric research techniques play a prevalent and multi-disciplinary role in life science research. In the past, scientists in wet labs generated the data, and computational researchers focused on creating tools for the analysis of those data. Computational researchers are now becoming more independent and taking leadership roles within biomedical projects, leveraging the increased availability of public data.

The path to scientifically sound biodiversity valuation in the context of the Global Biodiversity Framework.

Successful implementation of the Kunming-Montreal Global Biodiversity Framework requires identifying a process for measuring and valuing changes in biodiversity that build on the recognition that economics and valuation must play a key role in "halting and reversing" biodiversity loss. Here, we discuss considerations for a practical path to valuing changes in biodiversity. Framing changes in the value of biodiversity as a summary of changes in certain natural assets enables leveraging existing approaches and international standards associated with environmental-economic accounting.

Neuropsychological profile associated with financial exploitation vulnerability in older adults without dementia.

Reports of financial exploitation have steadily increased among older adults. Few studies have examined neuropsychological profiles for individuals vulnerable to financial exploitation, and existing studies have focused on susceptibility to scams, one specific type of financial exploitation. The current study therefore examines whether a general measure of financial exploitation vulnerability is associated with neuropsychological performance in a community sample.

Estimating Enzyme Expression and Metabolic Pathway Activity in -Infected and Uninfected Mice.

Evaluating changes in metabolic pathway activity is essential for studying disease mechanisms and developing new treatments, with significant benefits extending to human health. Here, we propose EMPathways2, a maximum likelihood pipeline that is based on the expectation-maximization algorithm, which is capable of evaluating enzyme expression and metabolic pathway activity level. We first estimate enzyme expression from RNA-seq data that is used for simultaneous estimation of pathway activity levels using enzyme participation levels in each pathway.

An eQTL-based approach reveals candidate regulators of LINE-1 RNA levels in lymphoblastoid cells.

Long interspersed element 1 (LINE-1; L1) are a family of transposons that occupy ~17% of the human genome. Though a small number of L1 copies remain capable of autonomous transposition, the overwhelming majority of copies are degenerate and immobile. Nevertheless, both mobile and immobile L1s can exert pleiotropic effects (promoting genome instability, inflammation, or cellular senescence) on their hosts, and L1's contributions to aging and aging diseases is an area of active research.

Microglia undergo sex-dimorphic transcriptional and metabolic rewiring during aging.

Microglia, the brain's resident macrophages, maintain brain homeostasis and respond to injury and infection. During aging they undergo functional changes, but the underlying mechanisms and their contributions to neuroprotection versus neurodegeneration are unclear. Previous studies suggested that microglia are sex dimorphic, so we compared microglial aging in mice of both sexes.

Early detection of emerging viral variants through analysis of community structure of coordinated substitution networks.

The emergence of viral variants with altered phenotypes is a public health challenge underscoring the need for advanced evolutionary forecasting methods. Given extensive epistatic interactions within viral genomes and known viral evolutionary history, efficient genomic surveillance necessitates early detection of emerging viral haplotypes rather than commonly targeted single mutations. Haplotype inference, however, is a significantly more challenging problem precluding the use of traditional approaches.

The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been defined as the greatest global health and socioeconomic crisis of modern times. While most people recover after being infected with the virus, a significant proportion of them continue to experience health issues weeks, months and even years after acute infection with SARS-CoV-2. This persistence of clinical symptoms in infected individuals for at least three months after the onset of the disease or the emergence of new symptoms lasting more than two months, without any other explanation and alternative diagnosis have been named long COVID, long-haul COVID, post-COVID-19 conditions, chronic COVID, or post-acute sequelae of SARS-CoV-2 (PASC).

Isolation and Characterization of Extracellular Vesicles Through Orthogonal Approaches for the Development of Intraocular EV Therapy.

Purpose: Isolating extracellular vesicles (EVs) with high yield, replicable purity, and characterization remains a bottleneck in the development of EV therapeutics. To address these challenges, the current study aims to establish the necessary framework for preclinical and clinical studies in the development of stem cell-derived intraocular EV therapeutics.

Methods: Small EVs (sEVs) were separated from the conditioned cell culture medium (CCM) of the human embryogenic stem cell-derived fully polarized retinal pigment epithelium (hESC-RPE-sEV) by a commercially available microfluidic tangential flow filtration (TFF) device ExoDisc (ED) or differential ultracentrifugation (dUC).

Large-scale integrative analysis of juvenile idiopathic arthritis for new insight into its pathogenesis.

Background: Juvenile idiopathic arthritis (JIA) is one of the most prevalent rheumatic disorders in children and is classified as an autoimmune disease (AID). While a robust genetic contribution to JIA etiology has been established, the exact pathogenesis remains unclear.

Methods: To prioritize biologically interpretable susceptibility genes and proteins for JIA, we conducted transcriptome-wide and proteome-wide association studies (TWAS/PWAS).

Subjective Age Moderates the Relationship Between Global Cognition and Susceptibility to Scams.

This study examined the interactive effect of subjective age on the relationship between global cognition and susceptibility to scams. Sixty-five participants underwent an assessment of global cognition (Mini Mental State Examination; MMSE), reported their perceived age (i.e.

Whole blood transcriptomics identifies subclasses of pediatric septic shock.

Background: Sepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies.

Sex-dimorphic expression of extracellular matrix genes in mouse bone marrow neutrophils.

The mammalian innate immune system is sex-dimorphic. Neutrophils are the most abundant leukocyte in humans and represent innate immunity's first line of defense. We previously found that primary mouse bone marrow neutrophils show widespread sex-dimorphism throughout life, including at the transcriptional level.

Sociodemographic profile associated with congenital heart disease among infants <1 year old.

Purpose: Congenital heart disease affects thousands of newborns each year in the United States. Previous United States-based research has explored how sociodemographic factors may impact health outcomes in infants with congenital heart disease; however, their impact on the incidence of congenital heart disease is unclear. We explored the sociodemographic profile related to congenital heart disease to help address health disparities that arise from race and social determinants of health.

Widespread sex dimorphism across single-cell transcriptomes of adult African turquoise killifish tissues.

The African turquoise killifish (Nothobranchius furzeri), the shortest-lived vertebrate that can be bred in captivity, is an emerging model organism for aging research. Here, we describe a multitissue, single-cell gene expression atlas of female and male blood, kidney, liver, and spleen. We annotate 22 cell types, define marker genes, and infer differentiation trajectories.

Transcriptomes of aging brain, heart, muscle, and spleen from female and male African turquoise killifish.

The African turquoise killifish is an emerging vertebrate model organism with great potential for aging research due to its naturally short lifespan. Thus far, turquoise killifish aging 'omic' studies have examined a single organ, single sex and/or evaluated samples from non-reference strains. Here, we describe a resource dataset of ribosomal RNA-depleted RNA-seq libraries generated from the brain, heart, muscle, and spleen from both sexes, as well as young and old animals, in the reference GRZ turquoise killifish strain.

An eQTL-based Approach Reveals Candidate Regulators of LINE-1 RNA Levels in Lymphoblastoid Cells.

Long interspersed element 1 (L1) are a family of autonomous, actively mobile transposons that occupy ~17% of the human genome. A number of pleiotropic effects induced by L1 (promoting genome instability, inflammation, or cellular senescence) have been observed, and L1's contributions to aging and aging diseases is an area of active research. However, because of the cell type-specific nature of transposon control, the catalogue of L1 regulators remains incomplete.

Quantification of race/ethnicity representation in Alzheimer's disease neuroimaging research in the USA: a systematic review.

Background: Racial and ethnic minoritized groups are disproportionately at risk for Alzheimer's Disease (AD), but are not sufficiently recruited in AD neuroimaging research in the United States. This is important as sample composition impacts generalizability of findings, biomarker cutoffs, and treatment effects. No studies have quantified the breadth of race/ethnicity representation in the AD literature.