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Bridging brain insulin resistance to Alzheimer's pathogenesis

2 months 3 weeks ago
Emerging evidence links type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), with brain insulin resistance (BIR) as a key factor. In a recent study, Lanzillotta et al. reveal that reduced biliverdin reductase-A (BVR-A) impairs glycogen synthase kinase 3β (GSK3β) phosphorylation, causing mitochondrial dysfunction and exacerbating brain insulin resistance in the progression of both T2DM and AD.
Wenqiang Chen

The role of PINK1-Parkin in mitochondrial quality control

2 months 3 weeks ago
Mitophagy mediated by the recessive Parkinson's disease genes PINK1 and Parkin responds to mitochondrial damage to preserve mitochondrial function. In the pathway, PINK1 is the damage sensor, probing the integrity of the mitochondrial import pathway, and activating Parkin when import is blocked. Parkin is the effector, selectively marking damaged mitochondria with ubiquitin for mitophagy and other quality-control processes. This selective mitochondrial quality-control pathway may be especially...
Derek P Narendra

Midlife dynamics of white matter architecture in lexical production

2 months 3 weeks ago
We aimed to examine the white matter changes associated with lexical production difficulties, beginning in midlife with increased naming latencies. To delay lexical production decline, middle-aged adults may rely on domain-general and language-specific compensatory mechanisms proposed by the LARA model (Lexical Access and Retrieval in Aging). However, the white matter changes supporting these mechanisms remains largely unknown. Using data from the CAMCAN cohort, we employed an unsupervised and...
Clément Guichet

The role of Klotho and sirtuins in sleep-related cardiovascular diseases: a review study

2 months 3 weeks ago
The prevalence of sleep disorders has been reported from 1.6% to 56.0%, worldwide. Sleep deprivation causes cardiovascular diseases (CVDs) including atherosclerosis, vascular aging, hypertension, heart dysfunction, reduced heart rate variability, and cardiac arrhythmia. Reduced tissue oxygen causes various CVDs by activating pro-inflammatory factors and increasing oxidative stress. Sleep disorders are more important and prevalent in older people and cause more severe cardiovascular...
Farzaneh Rostamzadeh

CRISPR-Cas9 screens reveal regulators of ageing in neural stem cells

2 months 3 weeks ago
Ageing impairs the ability of neural stem cells (NSCs) to transition from quiescence to proliferation in the adult mammalian brain. Functional decline of NSCs results in the decreased production of new neurons and defective regeneration following injury during ageing^(1-4). Several genetic interventions have been found to ameliorate old brain function^(5-8), but systematic functional testing of genes in old NSCs-and more generally in old cells-has not been done. Here we develop in vitro and in...
Tyson J Ruetz

A scoping review of barriers to accessing aged care services for older adults from culturally and linguistically diverse communities in Australia

2 months 3 weeks ago
The ageing population of the culturally and linguistically diverse (CALD) population is increasing in Australia. This is because the number of early migrants in Australia is ageing, coupled with increasing family reunification. This scoping review aimed to describe the nature and extent of research on the barriers to aged care services for CALD older adults in Australia using Penchansky and Thomas's Access to Care Framework of five A's dimensions: availability, accessibility, accommodation,...
Anthony Obinna Iwuagwu

LRRK2 regulates production of reactive oxygen species in cell and animal models of Parkinson's disease

2 months 3 weeks ago
Oxidative stress has long been implicated in Parkinson's disease (PD) pathogenesis, although the sources and regulation of reactive oxygen species (ROS) production are poorly defined. Pathogenic mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are associated with increased kinase activity and a greater risk of PD. The substrates and downstream consequences of elevated LRRK2 kinase activity are still being elucidated, but overexpression of mutant LRRK2 has been associated with...
Matthew T Keeney

Nucleoporin Nsp1 surveils the phase state of FG-Nups

2 months 3 weeks ago
Transport through the nuclear pore complex (NPC) relies on intrinsically disordered FG-nucleoporins (FG-Nups) forming a selective barrier. Away from the NPC, FG-Nups readily form condensates and aggregates, and we address how this behavior is surveilled in cells. FG-Nups, including Nsp1, together with the nuclear transport receptor Kap95, form a native daughter cell-specific cytosolic condensate in yeast. In aged cells, this condensate disappears as cytosolic Nsp1 levels decline. Biochemical...
Tegan A Otto

Complexity of confined water vitrification and its glass transition temperature

2 months 3 weeks ago
The ability of vitrification when crossing the glass transition temperature (T(g)) of confined and bulk water is crucial for myriad phenomena in diverse fields, ranging from the cryopreservation of organs and food to the development of cryoenzymatic reactions, frost damage to buildings, and atmospheric water. However, determining water's T(g) remains a major challenge. Here, we elucidate the glass transition of water by analyzing the calorimetric behavior of nano-confined water across various...
Jorge H Melillo

Helios-Illuminating the way for lymphocyte self-control

2 months 3 weeks ago
Transcription factor Helios, encoded by the IKZF2 gene, has an important role in regulatory T cells by stabilizing their suppressive phenotype. While Helios is prominently expressed in regulatory T cells, its expression extends beyond to include effector T cells, follicular regulatory T cells, B cells, and innate-like lymphocyte populations. Recent characterizations of patients with inborn error of immunity due to damaging IKZF2 variants coupled with translational research on lymphocytes from...
Iivo Hetemäki