Spatio-temporal regulation of Wnt and retinoic acid signaling by tbx16/spadetail during zebrafish mesoderm differentiation

<p>Abstract</p> <p>Background</p> <p>A complex network of signaling pathways and transcription factors regulates vertebrate mesoderm development. Zebrafish mutants provide a powerful tool for examining the roles of individual genes in such a network. <it>spadetail (spt) </it>is a mutant with a lesion in <it>tbx16</it>, a T-box transcription factor involved in mesoderm development; the mutant phenotype includes disrupted primitive red blood cell formation as well as disrupted somitogenesis. Despite much recent progress, the downstream targets of <it>tbx16 </it>remain incompletely understood. The current study was carried out to test whether any of the five major signaling pathways are regulated by <it>tbx16 </it>during two specific stages of mesoderm development: primitive red blood cell formation in the intermediate mesoderm and somite formation in the tail paraxial mesoderm. This test was performed using Gene Set Enrichment Analysis, which identifies coordinated changes in expression among <it>a priori </it>sets of genes associated with biological features or processes.</p> <p>Results</p> <p>Our Gene Set Enrichment Analysis results identify Wnt and retinoic acid signaling as likely downstream targets of <it>tbx16 </it>in the developing zebrafish intermediate mesoderm, the site of primitive red blood cell formation. In addition, such results identify retinoic acid signaling as a downstream target of <it>tbx16 </it>in the developing zebrafish posterior somites. Finally, using candidate gene identification and <it>in situ </it>hybridization, we provide expression domain information for 25 additional genes downstream of <it>tbx16 </it>that are outside of both pathways; 23 were previously unknown downstream targets of <it>tbx16</it>, and seven had previously uncharacterized expression in zebrafish.</p> <p>Conclusions</p> <p>Our results suggest that (1) <it>tbx16 </it>regulates Wnt signaling in the developing zebrafish intermediate mesoderm, the site of primitive red blood cell formation, and (2) <it>tbx16 </it>regulates retinoic acid signaling at two distinct embryonic locations and developmental stages, which may imply ongoing spatio-temporal regulation throughout mesoderm development.</p

The Bible Story Producer App

The Bible Story Producer team at Cedarville University has been spending the past year on the Bible Story Producer app for Android. This app is a tool whose purpose is to facilitate the translation of Bible stories by bilingual laypersons in places where the Bible is unavailable in the vernacular. The aim of the app is to facilitate the oral translation of Bible stories transmitted as templates consisting of voice narration in a Language of Wider Communication (LWC). The narration is accompanied by a series of high-quality illustrations animated by the Ken Burns (pan and zoom) effect. An instance of oral translation may not involve writing down the translated words since some languages do not yet have an alphabet. Field testing has, so far, shown the controversial notion of oral translation to be effective. In our presentation, we will discuss the translation process that our client introduced to us as well as different implementation decisions that went into the making of the app

Phylogenomics Reveals Ancient Gene Tree Discordance in the Amphibian Tree of Life

Molecular phylogenies have yielded strong support for many parts of the amphibian Tree of Life, but poor support for the resolution of deeper nodes, including relationships among families and orders. To clarify these relationships, we provide a phylogenomic perspective on amphibian relationships by developing a taxon-specific Anchored Hybrid Enrichment protocol targeting hundreds of conserved exons which are effective across the class. After obtaining data from 220 loci for 286 species (representing 94% of the families and 44% of the genera), we estimate a phylogeny for extant amphibians and identify gene tree–species tree conflict across the deepest branches of the amphibian phylogeny. We perform locus-by-locus genealogical interrogation of alternative topological hypotheses for amphibian monophyly, focusing on interordinal relationships. We find that phylogenetic signal deep in the amphibian phylogeny varies greatly across loci in a manner that is consistent with incomplete lineage sorting in the ancestral lineage of extant amphibians. Our results overwhelmingly support amphibian monophyly and a sister relationship between frogs and salamanders, consistent with the Batrachia hypothesis. Species tree analyses converge on a small set of topological hypotheses for the relationships among extant amphibian families. These results clarify several contentious portions of the amphibian Tree of Life, which in conjunction with a set of vetted fossil calibrations, support a surprisingly younger timescale for crown and ordinal amphibian diversification than previously reported. More broadly, our study provides insight into the sources, magnitudes, and heterogeneity of support across loci in phylogenomic data sets

Exome screening to identify loss-of-function mutations in the rhesus macaque for development of preclinical models of human disease

BACKGROUND: Exome sequencing has been utilized to identify genetic variants associated with disease in humans. Identification of loss-of-function mutations with exome sequencing in rhesus macaques (Macaca mulatta) could lead to valuable animal models of genetic disease. Attempts have been made to identify variants in rhesus macaques by aligning exome data against the rheMac2 draft genome. However, such efforts have been impaired due to the incompleteness and annotation errors associated with rheMac2. We wished to determine whether aligning exome reads against our new, improved rhesus genome, MacaM, could be used to identify high impact, loss-of-function mutations in rhesus macaques that would be relevant to human disease. RESULTS: We compared alignments of exome reads from four rhesus macaques, the reference animal and three unrelated animals, against rheMac2 and MacaM. Substantially more reads aligned against MacaM than rheMac2. We followed the Broad Institute’s Best Practice guidelines for variant discovery which utilizes the Genome Analysis Toolkit to identify high impact mutations. When rheMac2 was used as the reference genome, a large number of apparent false positives were identified. When MacaM was used as the reference genome, the number of false positives was greatly reduced. After examining the variant analyses conducted with MacaM as reference genome, we identified two putative loss-of-function mutations, in the heterozygous state, in genes related to human health. Sanger sequencing confirmed the presence of these mutations. We followed the transmission of one of these mutations (in the butyrylthiocholine gene) through three generations of rhesus macaques. Further, we demonstrated a functional decrease in butyrylthiocholinesterase activity similar to that observed in human heterozygotes with loss-of-function mutations in the same gene. CONCLUSIONS: The new MacaM genome can be effectively utilized to identify loss-of-function mutations in rhesus macaques without generating a high level of false positives. In some cases, heterozygotes may be immediately useful as models of human disease. For diseases where homozygous mutants are needed, directed breeding of loss-of-function heterozygous animals could be used to create rhesus macaque models of human genetic disease. The approach we describe here could be applied to other mammals, but only if their genomes have been improved beyond draft status. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2509-5) contains supplementary material, which is available to authorized users

Social change and the family: Comparative perspectives from the west, China, and South Asia

This paper examines the influence of social and economic change on family structure and relationships: How do such economic and social transformations as industrialization, urbanization, demographic change, the expansion of education, and the long-term growth of income influence the family? We take a comparative and historical approach, reviewing the experiences of three major sociocultural regions: the West, China, and South Asia. Many of the changes that have occurred in family life have been remarkably similar in the three settings—the separation of the workplace from the home, increased training of children in nonfamilial institutions, the development of living arrangements outside the family household, increased access of children to financial and other productive resources, and increased participation by children in the selection of a mate. While the similarities of family change in diverse cultural settings are striking, specific aspects of change have varied across settings because of significant pre-existing differences in family structure, residential patterns of marriage, autonomy of children, and the role of marriage within kinship systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45661/1/11206_2005_Article_BF01124383.pd