The endocytic adaptor AP-2 maintains Purkinje cell function by balancing cerebellar parallel and climbing fiber synapses.

The loss of cerebellar Purkinje cells is a hallmark of neurodegenerative movement disorders, but the mechanisms remain enigmatic. We show that endocytic adaptor protein complex 2 (AP-2) is crucial for Purkinje cell survival. Using mouse genetics, viral tracing, calcium imaging, and kinematic analysis, we demonstrate that loss of the AP-2 μ subunit in Purkinje cells leads to early-onset ataxia and progressive degeneration.

Periodontal pathogens and obesity in the context of cardiovascular risks across age groups.

Background: Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity among noncommunicable diseases. Over the past decade, there has been a notable increase in the prevalence of CVDs among young individuals. Obesity, a well-known risk factor for CVDs, is also associated with various comorbidities that may contribute to cardiovascular risk.

Alanine mutation of the targeting subunit of the myosin phosphatase, MYPT1 at threonine 696 reduces cGMP responsiveness of mouse femoral arteries.

The femoral artery (FA) is the largest vessel in the hindlimb circulation and its proper tone regulation ensures adequate blood supply to muscle tissue. We investigated whether an alanine mutation of the targeting subunit of myosin-light-chain-phosphatase (MLCP), MYPT1, at threonine 696 (MYPT1-T696A/+), decisive for enzyme acivity, affects the responsiveness of young and old FAs (y-FAs and o-FAs) to activation of nitric-oxide/soluble-guanylate-cyclase/protein-kinase-G cascade (NO/sGC/PKG). Contractile responses of the vessels were measured by wire myography.

Sequential Activation of Lateral Hypothalamic Neuronal Populations during Feeding and Their Assembly by Gamma Oscillations.

Neural circuits supporting innate behaviors, such as feeding, exploration, and social interaction, intermingle in the lateral hypothalamus (LH). Although previous studies have shown that individual LH neurons change their firing relative to the baseline during one or more behaviors, the firing rate dynamics of LH populations within behavioral episodes and the coordination of behavior-related LH populations remain largely unknown. Here, using unsupervised graph-based clustering of LH neurons firing rate dynamics in freely behaving male mice, we identified distinct populations of cells whose activity corresponds to feeding, specific times during feeding bouts, or other innate behaviors-social interaction and novel object exploration.

Diet and the Gut Microbiome as Determinants Modulating Metabolic Outcomes in Young Obese Adults.

Obesity, along with metabolic disorders such as dyslipidemia and insulin resistance, increases the risk of cardiovascular disease, diabetes, various cancers, and other non-communicable diseases, thereby contributing to higher mortality rates. The intestinal microbiome plays a crucial role in maintaining homeostasis and influencing human metabolism. This study enrolled 82 young obese individuals, who were stratified into groups with or without metabolic disturbances.