Skip to main content

Aggregator

AAV vectors for specific and efficient gene expression in microglia

7 months 3 weeks ago
Microglia are crucial targets for therapeutic interventions in diseases like Alzheimer's and stroke, but efficient gene delivery to these immune cells is challenging. We developed an adeno-associated virus (AAV) vector that achieves specific and efficient gene delivery to microglia. This vector incorporates the mIba1 promoter, GFP, miRNA target sequences (miR.Ts), WPRE, and poly(A) signal. Positioning miR.Ts on both sides of WPRE significantly suppressed non-microglial expression, achieving over...
Ryo Aoki

DNA large fragment deleting by compact, sequence-motif-free and specific TaqTth-hpRNA assisted with the microhomology-mediated end joining pathway

7 months 3 weeks ago
A DNA editing tool TaqTth-hpRNA was developed in this study, composed of a compact recombinant TaqTth nuclease (832 aa) and a simple hairpin-RNA guiding probe (hpRNA). In vitro biochemical studies showed the TaqTth-hpRNA efficiently cleaves artificially synthesized single-stranded DNA without stringent sequence motif like protospacer adjacent motif (PAM). It can also cleave the genomic DNA of Escherichia coli with ∼80% efficiency. The TaqTth-hpRNA cleavage of genomic DNA in mammalian cells...
Yu Liu

Heart Rate Dynamics During Localized Upper-Extremity Function as a Novel Measure of Cardiac Autonomic Dysfunction: Investigation of Aging- and Disease-Related Alterations

7 months 3 weeks ago
Introduction Cardiac autonomic dysfunction reduces the cardiac system's ability to respond to stressors and is prevalent in aging and diseases, especially cardiovascular diseases like aortic stenosis (AS). Heart rate variability (HRV) is a common measure for evaluating parasympathetic activity and cardiac autonomic function; similarly, heart rate (HR) changes during exercise are utilized in determining cardiac health. However, directly measuring HR parameters from an electrocardiogram (ECG) is...
Kübra Akbaş

Exercise as elixir to combat cardiovascular ageing

7 months 3 weeks ago
The global demographic shift towards an ageing population has rendered cardiovascular ageing and its associated pathologies a growing challenge for health. Emerging evidence highlights the critical role of exercise in mitigating age-associated cardiovascular alterations in structure and function and preventing ageing-associated cardiovascular diseases. However, the precise molecular mechanisms mediating these exercise-induced benefits in promoting healthy cardiovascular ageing remains...
Zihang Feng

Activation of a Src-JNK pathway in unscheduled endocycling cells of the Drosophila wing disc induces a chronic wounding response

7 months 3 weeks ago
The endocycle is a specialized cell cycle during which cells undergo repeated G/S phases to replicate DNA without division, leading to large polyploid cells. The transition from a mitotic cycle to an endocycle can be triggered by various stresses, which results in unscheduled, or induced endocycling cells (iECs). While iECs can be beneficial for wound healing, they can also be detrimental by impairing tissue growth or promoting cancer. However, the regulation of endocycling and its role in...
Yi-Ting Huang

Stress granule clearance mediated by V-ATPase-interacting protein NCOA7 mitigates ovarian aging

7 months 3 weeks ago
Reproductive longevity is essential for female fertility and healthy aging; however, the role of stress response, especially stress granule accumulation, in ovarian aging remains elusive and interventions are lacking. Here, we identified deleterious mutations and decreased expression of NCOA7, a stress-response protein related to granulosa cell senescence in women with physiological and pathological ovarian aging. NCOA7 deletion accelerates oxidative stress-related cellular senescence, ovarian...
Ting Dong

Comparison of the acute effects of breaking up prolonged sitting time with single-task or a dual-task walking on cognitive function and cerebral blood flow in older adults: a randomized crossover trial

7 months 3 weeks ago
This randomized cross-over study examined the acute effects of single-task or dual-task walking physical activity (PA) breaks of prolonged sitting among healthy older adults on cognitive performance and cerebral blood flow velocity (CBFv). Twenty-seven healthy older adults (69.4 ± 5.6 years, 25 female) were randomly assigned to engage in three experimental conditions (i.e., control, single-task, and dual-task walking), each one on a different day. All conditions included 3 h of sitting time,...
Paolo M Cunha

Understanding frailty in aging: a multidimensional perspective from Northern Iran

7 months 3 weeks ago
CONCLUSION: Frailty is highly prevalent among older adults in Sari and is associated with a complex interplay of demographic, socioeconomic, and health-related factors. Given the modifiable nature of certain risk factors, targeted interventions focusing on social support, financial stability, and physical activity are essential to mitigate frailty and enhance the quality of life in Iran's aging population.
Masoud Gharib

Disruption of hippocampal-prefrontal neural dynamics and risky decision-making in a mouse model of Alzheimer's disease

7 months 3 weeks ago
This study investigates how amyloid pathology influences hippocampal-prefrontal neural dynamics and decision-making in Alzheimer's disease (AD) using 5XFAD mice, a well-established model system characterized by pronounced early amyloid pathology. Utilizing ecologically relevant "approach food-avoid predator" foraging tasks, we show that 5XFAD mice exhibit persistent risk-taking behaviors and reduced adaptability to changing threat conditions, indicative of impaired decision-making....
Eun Joo Kim

A spatial imaging-transcriptomics paradigm for deciphering the molecular basis of microscopic MRI in the normal brain and Alzheimer's disease

7 months 3 weeks ago
Imaging genomics offers powerful links between genetics and neuroimaging phenotypes, but conventional methods often lack spatial correspondence. We introduce spatial imaging-transcriptomics, a paradigm that directly integrates magnetic resonance imaging (MRI) and spatially resolved transcriptomics (ST) with matched resolution from the same brain through spatially co-registered maps. We apply this framework to wild-type and Alzheimer's disease (AD) mouse models to uncover the molecular...
Yiqi Shen

In situ cryo-ET visualization of mitochondrial depolarization and mitophagic engulfment

7 months 3 weeks ago
Defective mitochondrial quality control in response to loss of mitochondrial membrane polarization is implicated in Parkinson's disease by mutations in PINK1 and PRKN. Parkin-expressing U2 osteosarcoma (U2OS) cells were treated with the depolarizing agents oligomycin and antimycin A (OA) and subjected to cryo-focused ion beam milling and in situ cryo-electron tomography. Mitochondria were fragmented and devoid of matrix calcium phosphate crystals. Phagophores were visualized, with bridge-like...
Kevin Rose

Altered translation elongation contributes to key hallmarks of aging in the killifish brain

7 months 3 weeks ago
Aging is a major risk factor for neurodegeneration and is characterized by diverse cellular and molecular hallmarks. To understand the origin of these hallmarks, we studied the effects of aging on the transcriptome, translatome, and proteome in the brain of short-lived killifish. We identified a cascade of events in which aberrant translation pausing led to altered abundance of proteins independently of transcriptional regulation. In particular, aging caused increased ribosome stalling and...
Domenico Di Fraia

Elevated ubiquitin phosphorylation by PINK1 contributes to proteasomal impairment and promotes neurodegeneration

7 months 3 weeks ago
Ubiquitin (Ub), a central regulator of protein turnover, can be phosphorylated by PINK1 (PTEN-induced putative kinase 1) to generate S65-phosphorylated ubiquitin (pUb). Elevated pUb levels have been observed in aged human brains and in Parkinson's disease, but the mechanistic link between pUb elevation and neurodegeneration remains unclear. Here, we demonstrate that pUb elevation is a common feature under neurodegenerative conditions, including Alzheimer's disease, aging, and ischemic injury. We...
Cong Chen