Hsurichards9793

Craniosynostosis (CS) is a major birth defect in which one or more skull sutures fuse prematurely. We previously performed a genome-wide association study (GWAS) for sagittal non-syndromic CS (sNCS), identifying associations downstream from BMP2 on 20p12.3 and intronic to BBS9 on 7p14.3; analyses of imputed variants in DLG1 on 3q29 were also genome-wide significant. We followed this work with a GWAS for metopic non-syndromic NCS (mNCS), discovering a significant association intronic to BMP7 on 20q13.31. In the current study, we sequenced the associated regions on 3q29, 7p14.3, and 20p12.3, including two candidate genes (BMP2 and BMPER) near some of these regions in 83 sNCS child-parent trios, and sequenced regions on 7p14.3 and 20q13.2-q13.32 in 80 mNCS child-parent trios. These child-parent trios were selected from the original GWAS cohorts if the probands carried at least one copy of the top associated GWAS variant (rs1884302 C allele for sNCS; rs6127972 T allele for mNCS). Many of the variants sequenced in these targeted regions are strongly predicted to be within binding sites for transcription factors involved in craniofacial development or bone morphogenesis. Variants enriched in more than one trio and predicted to be damaging to gene function are prioritized for functional studies.Colorectal cancer is the third most frequently encountered cancer worldwide. While current chemotherapeutics help to manage the disease to some extent, they have eluded achieving complete remission and are limited by their severe side effects. This warrants exploration of novel agents that are efficacious with anticipation of minimal adverse effects. In the current study, casticin, a tetramethoxyflavone, was tested for its ability to inhibit the viability of three human colorectal cancer cells adenocarcinoma (DLD-1, Caco-2 cell lines) and human colorectal carcinoma cells (HCT116 cell line). Casticin showed potent inhibition of viability of DLD-1 and HCT116 cells. Clonogenic assay performed in DLD-1 cells revealed that casticin impeded the colony-forming efficiency of the cells, suggesting its impact on the proliferation of these cells. Further, a sustained effect of the inhibitory action upon withdrawal of the treatment was observed. Elucidation of the mechanism of action revealed that casticin impacted the extrinsic programmed cell death pathway, leading to an increase in apoptotic cells. Further, Bcl-2, the key moiety of cell survival, was affected. Notably, a significant number of cells were arrested in the G2/M phase of the cell cycle in DLD-1 cells. Due to the multifaceted action of casticin, we envision that treatment with casticin could provide an efficacious treatment option for colorectal adenocarcinomas with minimal side effects.Neurogenomic changes induced by maternal immune activation (MIA) during gestation and the social stress of weaning can alter brain plasticity in the hippocampus of offspring. The present study furthers the understanding of how these stressors impact hippocampus gene networks. The hippocampus transcriptome was profiled in pigs that were either exposed to MIA or not and were weaned or nursed. Overall, 1576 genes were differentially expressed (FDR-adjusted p-value < 0.05 and |log2 (fold change between pig groups)| > 1.2) in response to the main and interacting effects of MIA, weaning, and sex. Functional analysis identified 17 enriched immunological and neurological pathways in the Kyoto Encyclopedia of Genes and Genomes database. The enrichment of the terpenoid backbone biosynthesis pathway was characterized by genes under-expressed in MIA relative to non-MIA exposed, males relative to females, and weaned relative to nursed pigs. On the other hand, the enrichment of drug addiction pathways was characterized by gene over-expression in MIA relative to non-exposed pigs. Our results indicate that weaning and sex can modify the effects of MIA on the offspring hippocampus. this website This knowledge can aid in precise identification of molecular targets to reduce the prolonged effects of pre- and postnatal stressors.As more molecular-targeted drugs for advanced non-small cell lung cancer are brought to market, batch tests for the identification of gene mutations are needed at initial diagnosis. However, since current gene panel tests require a sufficient amount of tissue sample, there are many instances where panel tests cannot be performed. Therefore, we have developed a highly sensitive next generation sequencing (NGS) panel test to facilitate cytological specimens. Herein, we describe three cases positive for epidermal growth factor receptor (EGFR) exon 19 deletion, MET exon 14 skipping, and KRAS G12A using NGS analysis from sputum. In each case, genetic information was consistent with companion diagnostic analysis obtained from tissue samples collected under bronchoscopy. In cases of EGFR and MET mutations, the corresponding tyrosine kinase inhibitors were highly effective. This is the first report to demonstrate that a novel panel test could detect gene mutations in sputum samples in clinical practice and compare the gene allele ratio with the sample directly collected from the lesion.Skraban-Deardorff syndrome is a rare autosomal dominant genetic disease caused by variants in the WDR26 gene. Here, we report two Chinese patients diagnosed with Skraban-Deardorff syndrome caused by novel de novo, heterozygous pathogenic WDR26 variants c.977delA (p. 12 N326Ifs*2) and c.1020-2A>G (p. R340Sfs*29). Their clinical features were characterized by intellectual disability (ID), developmental delay, abnormal facial features and the absence of early-onset seizure, which expands the phenotype spectrum associated with Skraban-Deardorff syndrome. By comparing our cases with current reported cases of WDR26-related intellectual disability, we suggest that developmental delay, particularly in speech, and facial features including rounded palpebral fissures, depressed nasal root, full nasal tip and abnormal gums, represent the prominent clinical phenotypes for diagnosis of Skraban-Deardorff syndrome. Together, WDR26 variants and 1q41q42 deletions should feature prominently on the differential diagnosis of ID with distinctive facial features.Salmonella Typhimurium (ST) is a foodborne pathogen that adversely affects the health of both animals and humans. Since poultry is a common source and carrier of the disease, controlling ST infection in chickens will have a protective impact on human health. In the current study, Beijing-You (BY) and Cobb chicks (5-day-old specific-pathogen-free) were orally challenged by 2.4 × 1012 CFU ST, spleen transcriptome was conducted 1 day post-infection (DPI) to identify gene markers and pathways related to the immune system. A total of 775 significant differentially expressed genes (DEGs) in comparisons between BY and Cobb were identified, including 498 upregulated and 277 downregulated genes (fold change ≥2.0, p < 0.05). Several immune response pathways against Salmonella were enriched, including natural killer-cell-mediated-cytotoxicity, cytokine-cytokine receptor interaction, antigen processing and presentation, phagosomes, and intestinal immune network for IgA production, for both BY and Cobb chickens. The BY chicks showed a robust response for clearance of bacterial load, immune response, and robust activation of phagosomes, resulting in ST resistance. These results confirmed that BY breed more resistance to ST challenge and will provide a better understanding of BY and Cobb chickens' susceptibility and resistance to ST infection at the early stages of host immune response, which could expand the known intricacies of molecular mechanisms in chicken immunological responses against ST. Pathways induced by Salmonella infection may provide a novel approach to developing preventive and curative strategies for ST, and increase inherent resistance in animals through genetic selection.The hypothesis that the evolution of humans involves hybridization between diverged species has been actively debated in recent years. We present the following novel evidence in support of this hypothesis the analysis of nuclear pseudogenes of mtDNA ("NUMTs"). NUMTs are considered "mtDNA fossils" as they preserve sequences of ancient mtDNA and thus carry unique information about ancestral populations. Our comparison of a NUMT sequence shared by humans, chimpanzees, and gorillas with their mtDNAs implies that, around the time of divergence between humans and chimpanzees, our evolutionary history involved the interbreeding of individuals whose mtDNA had diverged as much as ~4.5 Myr prior. This large divergence suggests a distant interspecies hybridization. Additionally, analysis of two other NUMTs suggests that such events occur repeatedly. Our findings suggest a complex pattern of speciation in primate/human ancestors and provide one potential explanation for the mosaic nature of fossil morphology found at the emergence of the hominin lineage. A preliminary version of this manuscript was uploaded to the preprint server BioRxiv in 2017 (10.1101/134502).Muskoxen (Ovibos moschatus) are Arctic species within the Caprinae subfamily that are economically and culturally significant to northern Indigenous communities. Low genetic diversity from repeated genetic bottlenecks, coupled with the effects of Arctic warming (e.g., heat stress, changing forage, pathogen range expansions), present conservation concerns for this species. Reference genome assemblies enhance our ecological and evolutionary understanding of species (which in turn aid conservation efforts). Herein, we provide a full draft reference genome of muskox using Illumina Hiseq data and cross-species scaffolding. The final reference assembly yielded a genome of 2,621,890,883 bp in length, a scaffold N50 of ~13.2 million, and an annotation identifying ~19.3 k genes. The muskox genome assembly and annotation were then used to reconstruct a phylogenetic tree which estimated muskoxen diverged from other ungulate species~12 Mya. To gain insight into the demographic history of muskoxen we also performed pairwise sequentially Markovian coalescent (PSMC) that identified two population bottlenecks coinciding with major glaciation events contributing to the notoriously low genetic variation observed in muskoxen. Overall, this genome assembly provides a foundation for future population genomic studies, such as latitudinal analyses, to explore the capacity of muskoxen to adapt to rapidly changing environments.This research was carried out at the Experimental Farm of Sakha Agricultural Research Station, Sakha, Kafr El-Sheikh, Egypt, during the 2018-2020 rice-growing seasons to develop and evaluate four iso-cytoplasmic rice-restorer lines NRL79, NRL80, NRL81, and NRL82, as well as Giza 178, with ten new hybrids in order to estimate genotypic coefficient, phenotypic coefficient, heritability in a broad sense, and advantage over Giza 178 as a check variety (control) of new restorer lines. This study also estimated combining ability, gene action, better-parent heterosis (BP), mid-parents heterosis (MP), and standard heterosis (SH) over Egyptian Hybrid one (IR69A × Giza 178) as a check hybrid (control) for grain yield, agronomic traits, and some grain quality characters in restorer lines and hybrids. The percentage of advantage over commercial-variety Giza 178 (check) was significant, and highly significant among the newly developed restorer fertility lines for all the studied traits. This indicates that the selection is a highly effective factor in improving these traits.