SUMMARY Although Aβ peptides are causative agents in Alzheimer's disease (AD), the underlying mechanisms are still elusive. We report that Aβ42 induces a translational block by activating AMPK, thereby inhibiting the mTOR pathway. This translational block leads to widespread ER stress, which activates JNK3. JNK3 in turn phosphorylates APP at T668, thereby facilitating its endocytosis and subsequent processing. In support, pharmacologically blocking translation results in a significant increase in Aβ42 in a JNK3-dependent manner. Thus, JNK3 activation, which is increased in human AD cases and a familial AD (FAD) mouse model, is integral to perpetuating Aβ42 production. Concomitantly, deletion of JNK3 from FAD mice results in a dramatic reduction in Aβ42 levels and overall plaque loads and increased neuronal number and improved cognition. This reveals AD as a metabolic disease that is under tight control by JNK3.
Fusion between membranes is mediated by specific SNARE complexes. Here we report that fibroblasts survive the absence of the trans-Golgi network/early endosomal SNARE vti1a and the late endosomal SNARE vti1b with intact organelle morphology and minor trafficking defects. Because vti1a and vti1b are the only members of their SNARE subclass and the yeast homolog Vti1p is essential for cell survival, these data suggest that more distantly related SNAREs acquired the ability to function in endosomal traffic during evolution. However, absence of vti1a and vti1b resulted in perinatal lethality. Major axon tracts were missing, reduced in size, or misrouted in Vti1a −/− Vti1b −/− embryos. Progressive neurodegeneration was observed in most Vti1a −/− Vti1b −/− peripheral ganglia. Neurons were reduced by more than 95% in Vti1a −/− Vti1b −/− dorsal root and geniculate ganglia at embryonic day 18.5. These data suggest that special demands for endosomal membrane traffic could not be met in Vti1a −/− Vti1b −/− neurons. Vti1a −/− and Vti1b −/− single deficient mice were viable without these neuronal defects, indicating that they can substitute for each other in these processes.endosome | neurite outgrowth | neuronal survival
This narrative review summarizes the latest advances in cerebral palsy and identifies where more research is required. Several studies on cerebral palsy were analyzed to generate a general idea of the prevalence of, risk factors associated with, and classification of cerebral palsy (CP). Different classification systems used for the classification of CP on a functional basis were also analyzed. Diagnosis systems used along with the prevention techniques were discussed. State-of-the-art treatment strategies for CP were also analyzed. Statistical distribution was performed based on the selected studies. Prevalence was found to be 2-3/1000 lives; the factors that can be correlated are gestational age and birth weight. The risk factors identified were preconception, prenatal, perinatal, and postnatal categories. According to the evidence, CP is classified into spastic (80%), dyskinetic (15%), and ataxic (5%) forms. Diagnosis approaches were based on clinical investigation and neurological examinations that include magnetic resonance imaging (MRI), biomarkers, and cranial ultrasound. The treatment procedures found were medical and surgical interventions, physiotherapy, occupational therapy, umbilical milking, nanomedicine, and stem cell therapy. Technological advancements in CP were also discussed. CP is the most common neuromotor disability with a prevalence of 2-3/1000 lives. The highest contributing risk factor is prematurity and being underweight. Several preventions and diagnostic techniques like MRI and ultrasound were being used. Treatment like cord blood treatment nanomedicine and stem cell therapy needs to be investigated further in the future to apply in clinical practice. Future studies are indicated in the context of technological advancements among cerebral palsy children.
Red pandas are known to be highly susceptible to endoparasites, which can have a prominent impact on the population dynamics of this endangered species. There are very limited published reports on prevalence and risk of parasites in wild populations of red panda, especially localized reports. This study attempts to provide an in-depth insight of the status of endoparasites in red pandas, which is critical for strengthening conservation efforts. A total of 272 fecal samples were collected through systematic sampling across the red panda distribution range in Nepal and coprological examination was completed using standard techniques. It was followed by an estimation of prevalence and mean intensity of parasites, as well as statistical analysis, which was carried out using R statistical software. Parasite prevalence was documented in 90.80% (n = 247) out of 272 samples examined which includes seven different species along with three genera of parasites belonging to Protozoans (3 species), Cestodes (1 genus, 1 species) and Nematodes (2 genera, 3 species). Nematodes predominated in all infected samples (87.62%). Prevalence of Ancyclostoma duodenale (n = 227, 70.06%), having a mean intensity of 3.45 ± 2.88 individuals per sample, was observed, followed by Ascaris lumbricoides (n = 19, 5.86%) and Entamoeba histolytica (n = 24, 7.41%). Eight variables for assessing the determinants of infestation were tested: protected areas; non-protected areas; aspect; elevation; slope; and distance to water sources, herding stations, and settlements. Only the settlement displayed significant association (β = −1534e−04, t = − 2.192, p = 0.0293) though each parasite species displayed dissimilar association with different variables. This study indicates the urgent need of improving existing herding practice through habitat zonation, rotational grazing, medication of livestock, and prohibition of open defecation within and around red panda habitat.
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