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Cell adhesion molecules (CAMs) are key players in the formation of neural circuits during development. The γ-protocadherins (γ-Pcdhs), a family of 22 CAMs encoded by the Pcdhg gene cluster, are known to play important roles in dendrite arborization, axon targeting, and synapse development. We showed previously that multiple γ-Pcdhs interact physically with the autism-associated CAM neuroligin-1, and inhibit the latter's ability to promote excitatory synapse maturation. Here, we show that γ-Pcdhs can also interact physically with the related neuroligin-2, and inhibit this CAM's ability to promote inhibitory synapse development. In an artificial synapse assay, γ-Pcdhs co-expressed with neuroligin-2 in non-neuronal cells reduce inhibitory presynaptic maturation in contacting hippocampal axons. Mice lacking the γ-Pcdhs from the forebrain (including the cortex, the hippocampus, and portions of the amygdala) exhibit increased inhibitory synapse density and increased co-localization of neuroligin-2 with inhibitory postsynaptic markers in vivo. These Pcdhg mutants also exhibit defective social affiliation and an anxiety-like phenotype in behavioral assays. Together, these results suggest that γ-Pcdhs negatively regulate neuroligins to limit synapse density in a manner that is important for normal behavior.

This paper demonstrates how addressing obesity is vital to achieving several of the Sustainable Development Goals and targets, especially target 3.4 on reducing premature mortality from non-communicable diseases.

Recent research by the UN notes that countries are not on schedule to achieve the SDGs. It is noted that obesity, neglected in earlier development goals and overlooked by global health funders and policymakers, is playing a role in major health and development issues. As such, the ROOTS framework developed by the World Obesity Federation offers a roadmap towards attaining several of the goals and targets. By making these connections, this paper shows that obesity is a relevant and essential component of the global development agenda and must be prioritised to successfully achieve targets related to NCD mortality.

Recent research by the UN notes that countries are not on schedule to achieve the SDGs. It is noted that obesity, neglected in earlier development goals and overlooked by global health funders and policymakers, is playing a role in major health and development issues. As such, the ROOTS framework developed by the World Obesity Federation offers a roadmap towards attaining several of the goals and targets. By making these connections, this paper shows that obesity is a relevant and essential component of the global development agenda and must be prioritised to successfully achieve targets related to NCD mortality.Mutations in parkin, which is encoded by the PARK2 gene, are associated with a rare form of Parkinson's disease called autosomal recessive juvenile parkinsonism (ARJP). Parkin is a member of RBR family of E3 ubiquitin ligase. Parkin contains a RING1-In-Between-Ring (IBR)-RING2 motif. The IBR domain is located at the C-terminal end of the parkin protein. Two zinc-binding sites are present in the IBR domain which shows zinc ion-dependent folding and maintains the orientation and geometry of RING domains. So, mutation in a zinc-binding region can be responsible for improper folding of parkin protein, which eventually affects the protein structure and function. Abnormalities in parkin protein increase the aggregation of mis-folded proteins in the brain cell. As a consequence, cellular toxicity occurs. The IBR domain also interacts with UbcH7 and UbcH8 proteins belonging to E2 protein family and facilitates synphilin-1, Sept5, and SIM2 protein ubiquitination. It is reported that missense mutation in parkin protein are responsible for autosomal recessive juvenile Parkinson disease. In this work, we first collected the missense mutations in the IBR domain from literature and sequence databases. Then, using various computational tools, we predicted their pathogenicity and involvements in causing possible changes in various protein properties. RRx-001 Evolutionary conservation of amino acids, solvent accessible surface areas, the physico-chemical properties, and changes of protein structure were analyzed. We, for the first time, analyzed the effects of these mutations in parkin to decipher the plausible molecular mechanism of Parkinson's disease.

Cryptosporidiosis is an opportunistic globally distributed parasitic disease caused by protozoan Cryptosporidium where its development is closely related to the host's immune status. New therapeutic agents are a high priority as chemotherapeutics are impractical and vaccines are unavailable for young as well as immune-compromised patients or animals. The current study was designed to evaluate the therapeutic effect of the internal white (albedo) and external yellow (flavedo) peels of Citrus maxima (C. maxima) as an alternative medicinal plant. MATERIALS AND METHODS Parasitological examination for oocysts in the stool was determined. Histopathological alterations and immunohistochemical expression of APC and cyclin D1 as well as an assessment of interferon-γ (IFN-γ) and interleukin 1β (IL-1β) in ileal tissues was carried out. In addition, the biochemical examination of serum albumin, globulin and liver enzymes were evaluated. Results revealed a significant decrease of oocysts count correlated with an amelioration of histopathological and immunohistochemical changes in ileal tissue with an enhancement of liver enzymes and inflammatory cytokines levels.

It could be concluded that treatment with C. maxima peel extracts have a potential therapeutic and an immunoregulatory efficacy against Cryptosporidiosis. Obtained results showed that the white peel was found to have more immunological effect that could significantly enhance inflammatory cytokines response towards normal status. Hence, it can be used in the daily animal diet to give protective effects against infection.

It could be concluded that treatment with C. maxima peel extracts have a potential therapeutic and an immunoregulatory efficacy against Cryptosporidiosis. Obtained results showed that the white peel was found to have more immunological effect that could significantly enhance inflammatory cytokines response towards normal status. Hence, it can be used in the daily animal diet to give protective effects against infection.