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Science, Volume 386, Issue 6719, October 2024.

Science, Volume 386, Issue 6719, October 2024.

Two evolutionary biologists speak to Science about the disparities in how some geographic areas are represented in biodiversity research

Two studies identify elusive protein complex with help from software developed by some of this year’s Nobel winners

The seeded growth of pathogenic protein aggregates underlies the pathogenesis of Alzheimer's disease (AD), but how this pathological cascade is initiated is not fully understood. Sporadic AD is linked genetically to apolipoprotein E (APOE) and other genes expressed in microglia related to immune, lipid, and endocytic functions. We generated a transgenic knockin mouse expressing HaloTag-tagged APOE and optimized experimental protocols for the biochemical purification of APOE, which enabled us to...

Alzheimer's disease (AD), the common form of dementia globally, is a complex condition including neurodegeneration; shares incompletely known pathogenesis. Signal transduction and biological activities, including cell metabolism, growth, and death are regulated by different signaling pathways including AKT/MAPK, Wnt, Leptin, mTOR, ubiquitin, Sirt1, and insulin. Absolute evidence linking specific molecular pathways with the genesis and/or progression of AD is still lacking. Changes in gut...

From 1990-2019, the burden of neurological disorders varied considerably across countries and regions. Psychiatric disorders, often emerging in early to mid-adulthood, are linked to late-life neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. Individuals with conditions such as Major Depressive Disorder, Anxiety Disorder, Schizophrenia, and Bipolar Disorder face up to four times higher risk of developing neurodegenerative disorders. Contrarily, 65 % of those with...

Chronic pain is prevalent among aging adults. Epidemiologic evidence has demonstrated that individuals with chronic pain have accelerated memory decline and increased probability of dementia. Neurophysiologic, molecular, and pharmacologic hypotheses have been proposed to explain the relationship between chronic pain and cognitive decline, but there remains currently limited evidence supporting any of these. Here, we integrate multi-omic data across human cohorts and rodent species and...

P21 activated kinase 6 (PAK6) is a serine-threonine kinase with physiological expression enriched in the brain and overexpressed in a number of human tumors. While the role of PAK6 in cancer cells has been extensively investigated, the physiological function of the kinase in the context of brain cells is poorly understood. Our previous work uncovered a link between PAK6 and the Parkinson's disease (PD)-associated kinase LRRK2, with PAK6 controlling LRRK2 activity and subcellular localization via...

The conserved mesencephalic astrocyte-derived neurotrophic factor (MANF) is known for protecting dopaminergic neurons and functioning in various other tissues. Previously, we showed that Caenorhabditis elegans manf-1 null mutants exhibit defects such as increased endoplasmic reticulum (ER) stress, dopaminergic neurodegeneration, and abnormal protein aggregation. These findings suggest an essential role for MANF in cellular processes. However, the mechanisms by which intracellular and...

Dielectrophoresis allows "dead" material to recover its activity.

Chronic pain is prevalent among aging adults. Epidemiologic evidence has demonstrated that individuals with chronic pain have accelerated memory decline and increased probability of dementia. Neurophysiologic, molecular, and pharmacologic hypotheses have been proposed to explain the relationship between chronic pain and cognitive decline, but there remains currently limited evidence supporting any of these. Here, we integrate multi-omic data across human cohorts and rodent species and...

CONCLUSIONS AND IMPLICATIONS: We found meaningful differences in home care transitions across several equity strata. Individuals with higher income have greater ability to access to private care, creating inequity in access to home care services. Gendered factors such as income and social support have important associations with home care use. Home care planning and policy must address the unique barriers and disadvantages diverse populations face to ensure equitable use of home care and promote...

The plasma concentration of the macroautophagy/autophagy inhibitor DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) increases with aging and body mass index (BMI). Both advanced age and obesity are among the most important risk factors for the development of cancer. We observed that patients with cancer predisposition syndromes due to mutations in BRCA1, BRCA2 and TP53 exhibit abnormally high plasma DBI/ACBP levels. Additionally, patients without known cancer predisposition...

Two themes are coming to the forefront in this decade: Cognitive impairment of an aging population and the quantum leap in developing artificial intelligence (AI). Both can be described as growing exponentially and presenting serious challenges. Although many questions have been addressed about the dangers of AI, we want to go beyond the fearful aspects of this topic and focus on the possible contribution of AI to solve the problem of chronic disorders of the elderly leading to cognitive...

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CONCLUSIONS: Embedding county service enrollment within a community ED is a cost neutral intervention that reached a population without previous services. Future plans include expansion of the program and evaluation of the program's ability to detect elder mistreatment and self-neglect.

Retrotransposons (RTEs) have been postulated to reactivate with age and contribute to aging through activated innate immune response and inflammation. Here, we analyzed the relationship between RTE expression and aging using published transcriptomic and methylomic datasets of human blood. Despite no observed correlation between RTE activity and chronological age, the expression of most RTE classes and families except short interspersed nuclear elements (SINEs) correlated with biological...

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