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aptation to extrauterine life. Most are benign and transient. Maternal age, type of delivery, and certain neonatal factors such as gestational age, birth weight, sex, and ethnicity are associated with specific findings.Alzheimer's disease (AD) is a neurodegenerative disorder and the major cause of dementia. According to predictions of the World Health Organization, more than 150 million people worldwide will suffer from dementia by 2050. An increasing number of studies have associated AD with type 2 diabetes mellitus (T2DM), since most of the features found in T2DM are also observed in AD, such as insulin resistance and glucose intolerance. In this sense, some bile acids have emerged as new therapeutic targets to treat AD and metabolic disorders. The taurine conjugated bile acid, tauroursodeoxycholic (TUDCA), reduces amyloid oligomer accumulation and improves cognition in APP/PS1 mice model of AD, and also improves glucose-insulin homeostasis in obese and type 2 diabetic mice. PF-04418948 Herein, we investigated the effect of TUDCA upon glucose metabolism in streptozotocin-induced AD mice model (Stz). The Stz mice that received 300 mg/kg TUDCA during 10 days (Stz + TUDCA), showed improvement in glucose tolerance and insulin sensitivity, reduced fasted and fed glycemia, increased islet mass and β-cell area, as well as increased glucose-stimulated insulin secretion, compared with Stz mice that received only PBS. Stz + TUDCA mice also displayed lower neuroinflammation, reduced protein content of amyloid oligomer in the hippocampus, improved memory test and increased protein content of insulin receptor β-subunit in the hippocampus. In conclusion, TUDCA treatment enhanced glucose homeostasis in the streptozotocin-induced Alzheimer's disease mice model, pointing this bile acid as a good strategy to counteract glucose homeostasis disturbance in AD pathology.Diabetes is a genetically heterogeneous disease, for which we are aiming to identify causative genes. Here, we report a missense mutation (c.T1424Cp.L475P) in ZYG11A identified by exome sequencing as segregating with hyperglycemia in a Thai family with autosomal dominant diabetes. ZYG11A functions as a target recruitment subunit of an E3 ubiquitin ligase complex that plays an important role in the regulation of cell cycle. We demonstrate an increase in cells arrested at G2/mitotic phase among beta-cells deficient for ZYG11A or overexpressing L475P-ZYG11A, which is associated with a decreased growth rate. This is the first evidence linking a ZYG11A mutation to hyperglycemia, and suggesting ZYG11A as a cell cycle regulator required for beta-cell growth. Since most family members were either overweight or obese, but only mutation carriers developed hyperglycemia, our data also suggests the ZYG11A mutation as a genetic factor predisposing obese individuals to beta-cell failure in maintenance of glucose homeostasis.Thyroglobulin (TG) is a homodimeric glycoprotein synthesized by the thyroid gland. To date, two hundred twenty-seven variations of the TG gene have been identified in humans. Thyroid dyshormonogenesis due to TG gene mutations have an estimated incidence of approximately 1 in 100,000 newborns. The clinical spectrum ranges from euthyroid to mild or severe hypothyroidism. The purpose of the present study was to identify and characterize new variants in the TG gene. We report an Argentine patient with congenital hypothyroidism, enlarged thyroid gland and low levels of serum TG. Sequencing of DNA, expression of chimeric minigenes as well as bioinformatics analysis were performed. DNA sequencing identified the presence of compound heterozygous mutations in the TG gene the maternal mutation consists of a c.3001+5G > A, whereas the paternal mutation consists of p.Arg296*. Minigen analysis of the variant c.3001+5A performed in HeLa, CV1 and Hek293T cell lines, showed a total lack of transcript expression. So, in order to validate that the loss of expression was caused by such variation, site-directed mutagenesis was performed on the mutated clone, which previously had a pSPL3 vector change, to give rise to a wild-type clone c.3001+5G, endorsing that the mutation c.3001+5G > A is the cause of the total lack of expression. In conclusion, we demonstrate that the c.3001+5G > A mutation causes a rare genotype, altering the splicing of the pre-mRNA. This work contributes to elucidating the molecular bases of TG defects associated with congenital hypothyroidism and expands our knowledge in relation to the pathologic roles of the position 5 in the donor splice site.Liver fibrosis is a dynamic wound-healing process associated with the deposition of extracellular matrix produced by myofibroblasts. HSCs activation, inflammation, oxidative stress, steatosis and aging play critical roles in the progression of liver fibrosis, which is correlated with the regulation of the peroxisome proliferator-activated receptor (PPAR) pathway. As nuclear receptors, PPARs reduce inflammatory response, regulate lipid metabolism, and inhibit fibrogenesis in the liver associated with aging. Thus, PPAR ligands have been investigated as possible therapeutic agents. Mounting evidence indicated that some PPAR agonists could reverse steatohepatitis and liver fibrosis. Consequently, targeting PPARs might be a promising and novel therapeutic option against liver fibrosis. This review summarizes recent studies on the role of PPARs on the pathogenesis and treatment of liver fibrosis.β-Catenin, a key transcriptional factor involved in the canonical Wnt signaling pathway, is regulated by a cascade of phosphorylations and plays a major role in the progression of triple-negative breast cancer (TNBC). However, the phosphorylation induced conformational changes in a β-Catenin is still poorly understood. Hence, we adopted a conventional molecular dynamics approach to study phosphorylations present in a sequence motif Ser 552 675 and Tyr670 of the β-Catenin domain and analyzed in terms of structural transitions, bond formation, and folding-misfolding conformations. Our results unveil the β-Catenin linear motif 549-555 (RRTSMGG) of armadillo repeats domain prefers order to disorder state. In contrast, helix C associated with 670-678 (YKKRLSVEL) motif prefers disorder to order upon phosphorylation of Ser 552 675 and Tyr670. In addition, the crucial secondary structural transition from α-helix to coil induced by phospho Ser552 and phospho Tyr670 of β-Catenin ARM domain connecting helix C modifies conformational diversity and binding affinities of the complex interaction in functional regulation significantly.