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Neuronal YTHDF2 suppresses innate immune activation in Aβ pathology by promoting m<sup>6</sup>A-dependent decay of cytosolic mitochondrial mRNAs

13 hours 51 minutes ago
Dysregulation of RNA m⁶A modification has been implicated in Alzheimer's disease (AD), but the molecular mechanisms remain largely unclear. Here, we identified the presence of m⁶A on mitochondria-encoded messenger RNAs (mt-mRNAs) in the brain, with elevated levels correlated with amyloid-β (Aβ) deposition. Under physiological conditions, cytosolic m⁶A-modified mt-Nd4 is recognized and degraded by the m⁶A reader protein YTHDF2, thereby preventing aberrant activation of the RIG-I-MAVS innate...
Wenqi Pan

Embryonic dopaminergic neuron activity sustains lifelong locomotion in Drosophila

13 hours 51 minutes ago
Locomotor skills arise early in life and are maintained throughout an animal's lifespan, yet how this continuity is achieved despite major neural remodeling remains unclear. Using Drosophila, which undergoes complete metamorphosis, we show that the activity of embryonically established dopaminergic neurons (DANs) is essential for locomotion across all developmental stages and adulthood. Through stage-specific behavioral assays, optogenetics, in vivo brain imaging, and fluorescent neuronal...
Aishwarya Padmanabhan

The pyruvate transporter hermes regulates autophagy and health by modulating ROS production

13 hours 51 minutes ago
Autophagy is a catabolic process that degrades cytoplasmic materials and is controlled by nutrient availability and signaling. The plasma membrane-associated pyruvate-solute carrier hermes (hrm) is required for regulation of the mechanistic target of rapamycin (mTOR) signaling and the activation of autophagy during development. Here, we screen for pyruvate-influencing genes that suppress the hrm mutant phenotype. We show that the inhibitory effect of hrm loss on autophagy depends on pyruvate...
Panagiotis D Velentzas

Prevalence of Unmet Service Needs and Associated Person-Reported Outcomes in Long-Term Services and Supports in the United States

13 hours 51 minutes ago
CONCLUSIONS: Consumer-reported unmet LTSS needs are frequent, vary greatly across care settings and funding programs, and are associated with poorer QoL-related outcomes; highlighting substantial system-level gaps in the fragmented LTSS landscape and the need for coordinated investments and structural reforms to better meet the needs of individuals relying on these services.
Romil R Parikh

Epigenetic Gene Networks Governing Immune State Transitions Across the Lifespan

13 hours 51 minutes ago
Immune function across development, tissue repair, aging, and disease depends not only on signaling pathways but also on epigenetic architectures that determine whether coordinated transcriptional programs can be accessed and resolved. Increasing evidence indicates that epigenetic gene networks regulate the accessibility and reversibility of semi-stable immune states, shaping plastic, homeostatic, reparative, and degenerative configurations. We propose the concept of epigenetic transition...
Ola A Al-Ewaidat

Amino acid and appendicular skeletal muscle mass insufficiency are associated to cognitive decline in Chinese population

13 hours 51 minutes ago
The relation between cognitive impairment and skeletal muscle mass or physical exercise has been broadly discussed. However, the underlying molecular features have not been systemically investigated. Essential amino acids are the key factors for skeletal muscle mass. In the current study, we investigated the abundance of metabolites in the serum of ~ 1500 participants in various cognitive status from multiple centers. Our study revealed a positive correlation between serum level of essential AA...
Ting Tang

Dysregulation of a novel autophagosome-mitochondria contact contributes to tauopathy-related neurodegeneration by disrupting autophagy

13 hours 51 minutes ago
Beyond their role in energy production, mitochondria also interact with other organelles through forming membrane contacts that serve as central hubs of cellular metabolism and signaling. Aberrant mitochondria-organelle communication has been implicated in various neurodegenerative diseases, but the underlying mechanisms and their pathological consequences remain poorly understood. Here, we reveal that tauopathy synapses exhibit excessive tethering of autophagosome/autophagic vacuole...
Nuo Jia

Artificial intelligence in geriatric healthcare: a scoping review

13 hours 51 minutes ago
CONCLUSIONS: Artificial intelligence holds significant promise for mitigating the global geriatric healthcare crisis exacerbated by demographic aging and nursing shortages. However, realizing its full potential requires a coordinated, multi-stakeholder approach to overcome the entrenched systemic, human, and social obstacles. The proposed roadmaps provide an actionable framework that may facilitate the development of artificial intelligence systems that are more efficient, equitable, and...
Yue Zhang

Near-gaze fixation promotes use of spin turns during walking: age-independent visuomotor effects with maladaptive behavioral consequences in older adults

13 hours 51 minutes ago
CONCLUSION: These findings identify gaze fixation as a key determinant of increased spin-turn use during turning in older adults, whereby constraining gaze to the near walking surface alters visual information available for step planning and promotes maladaptive turning strategy selection.
Juntaro Sakazaki