Elongator is a multi-subunit protein complex bearing six different protein subunits, Elp1 to -6, that are highly conserved among eukaryotes. Elp2 is the second major subunit of Elongator and, together with Elp1 and Elp3, form the catalytic core of this essential complex. Pathogenic variants that affect the structure and function of the Elongator complex may cause neurodevelopmental disorders. Here, we report on a new family with three children affected with a severe form of intellectual disability along with spastic tetraparesis, choreoathetosis, and self injury. Molecular genetic analyses reveal a homozygous missense variant in the ELP2 gene (NM_018255.4 (ELP2) c.1385G > A (p.Arg462Gln)), while in silico studies suggest a loss of electrostatic interactions that may contribute to the overall stability of the encoded protein. We also include a comparison of the patients with ELP2-related neurodevelopmental disorder to those previously reported in the literature. Apart from being affected with intellectual disability, we have extremely limited clinical knowledge about patients harboring ELP2 variants.  https://www.selleckchem.com/  Besides providing support to the causal role of p.Arg462Gln in ELP2-related neurodevelopmental disorder, we add self-injurious behavior to the clinical phenotypic repertoire of the disease.Chronic oxidative stress has been associated with several human ailments including the condition of aging. Extensive studies have shown the causal relationship between oxidative stress, aging, and cellular senescence. In this regard, forestalling or preventing senescence could delay the aging process as well as act as an intervention against premature aging. Hence, in the present study, we investigated the anti-senescence potential of Mangiferin (MGN) against Hydrogen peroxide (H2O2) induced premature senescence using human dermal fibroblast cells. Early passage human dermal fibroblasts cells were exposed to H2O2 (10 μM) for 15 days. In order to assess the anti-senescence property of MGN, cells were preconditioned with MGN (10 μM / 50 μM; 2 h) followed by addition of H2O2 (10 μM). H2O2 mediated induction of premature senescence was accompanied by elevated ROS, lowering of mitochondrial mass and membrane potential, changes in ATP content along with G0/G1 arrest and SA-β-gal expression. While, conditioning the cells with MGN lowered oxidative burden, stabilized mitochondrial membrane potential / mass and protected the cells against cell cycle arrest, ultimately rendering protection against premature senescence. The present findings showed that MGN might act as a potential cytoprotective nutraceutical that can prolong the onset of chronic oxidative stress mediated premature senescence.Recently, our group showed that Romidepsin, a histone deacetylase inhibitor (HDACi), suppressed diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in mice. In the present study, we investigated the effect of Romidepsin-treatment on gene expression levels of components of Bmp and Notch signaling pathways, which are both known to be aberrantly regulated in hepatocarcinogenesis. Total RNA from liver tissue samples and paraffin-embedded livers were retrieved from a recent experiment where C57BL/6 mice were treated with Romidepsin 10 months after DEN challenge and sacrificed 2 months later. RT qPCR was used for quantification of gene expression and immunohistochemistry for in situ protein detection. Regarding Bmp pathway, Romidepsin HCC-suppression was found to correlate significantly with Bmp2 and Bmp7 ligand up- and down-regulation, respectively. Intracellularly, Romidepsin-treated HCC mice exhibited a significant elevation of Bmp-inhibitor Smurf2 and Bmp-target gene Id3, as compared to the HCC untreated controls. Concerning Notch signaling, higher expression levels of ligands Jag1/Dll4, accompanied by a decreased expression of receptor Notch2, were identified in the Romidepsin-treated group. Τhe anti-oncogenic effect of Romidepsin, also correlated significantly with an increased expression of Hes1 target, as well as an up- and down-regulation of Klf4 and Sox9 transcription factors, respectively. Moreover, the cancer-related genes Snai2 and p21, known to be involved in many signaling pathways, including Bmp and Notch, were also found to be downregulated in Romidepsin-treated mice. Romidepsin HCC suppression is associated with gene expression deregulation of selective components of both Bmp and Notch signaling cascades.Tissue engineering is a rapidly developing field with many potential clinical applications in tissue and organ regeneration. The development of a mature and stable vasculature within these engineered tissues (ET) remains a significant obstacle. Currently, several growth factors (GFs) have been identified to play key roles within in vivo angiogenesis, including vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), FGF and angiopoietins. In this article we attempt to build on in vivo principles to review the single, dual and multiple GF release systems and their effects on promoting angiogenesis. We conclude that multiple GF release systems offer superior results compared to single and dual systems with more stable, mature and larger vessels produced. However, with more complex release systems this raises other problems such as increased cost and significant GF-GF interactions. Upstream regulators and pericyte-coated scaffolds could provide viable alternative to circumnavigate these issues.Rainbow trout (Onchorhynchus mykiss) is one of the most important freshwater aquaculture fish in Iran. It is necessary to develop available molecular marker such as SNPs, which represent a useful tool in detecting adaptive signals in populations and also parentage assignment for O. mykiss. Genetic architecture of broodstock populations is important for breeding programs, as it enables decisions on broodstock screening and genomic selection. In this study, 52 novel single nucleotide polymorphism (SNP) markers for O. mykiss were discovered and validated based on transcriptome sequencing, by means of paired-end sequencing in an Illumina HiSeq 2500 platform. The SNPs were identified through liver transcriptome sequencing from fifteen samples. The observed and expected heterozygosities ranged from 0.177 to 1.000 and 0.239 to 0.638, respectively. The minimum allele frequency (MAF) ranged from 0.166 to 0.489. Among these SNP loci, twenty-two loci showed significant departures from the Hardy-Weinberg equilibrium after Bonferroni correction (p  less then  0.