Profiling and Functional Analysis of mRNAs during Skeletal Muscle Differentiation in Goats

Skeletal myogenesis is a complicated biological event that involves a succession of tightly controlled gene expressions. In order to identify novel regulators of this process, we performed mRNA-Seq studies of goat skeletal muscle satellite cells (MuSCs) cultured under proliferation (GM) and differentiation (DM1/DM5) conditions. A total of 19,871 goat genes were expressed during these stages, 198 of which represented novel transcripts. Notably, in pairwise comparisons at the different stages, 2551 differentially expressed genes (DEGs) were identified (p p < 0.05). Functional enrichment analysis showed that DEGs were enriched for essential biological processes such as muscle structure development, muscle contraction, muscle cell development, striated muscle cell differentiation, and myofibril assembly, and were involved in pathways such as the MAPK, Wnt and PPAR signaling pathways. Moreover, the expression of eight DEGs (MYL2, DES, MYOG, FAP, PLK2, ADAM, WWC1, and PRDX1) was validated. These findings offer novel insights into the transcriptional regulation of skeletal myogenesis in goats

Complete Sequence and Analysis of Plastid Genomes of Two Economically Important Red Algae: <i>Pyropia haitanensis</i> and <i>Pyropia yezoensis</i>

<div><p>Background</p><p><i>Pyropia haitanensis</i> and <i>P. yezoensis</i> are two economically important marine crops that are also considered to be research models to study the physiological ecology of intertidal seaweed communities, evolutionary biology of plastids, and the origins of sexual reproduction. This plastid genome information will facilitate study of breeding, population genetics and phylogenetics.</p><p>Principal Findings</p><p>We have fully sequenced using next-generation sequencing the circular plastid genomes of <i>P. hatanensis</i> (195,597 bp) and <i>P. yezoensis</i> (191,975 bp), the largest of all the plastid genomes of the red lineage sequenced to date. Organization and gene contents of the two plastids were similar, with 211–213 protein-coding genes (including 29–31 unknown-function ORFs), 37 tRNA genes, and 6 ribosomal RNA genes, suggesting a largest coding capacity in the red lineage. In each genome, 14 protein genes overlapped and no interrupted genes were found, indicating a high degree of genomic condensation. <i>Pyropia</i> maintain an ancient gene content and conserved gene clusters in their plastid genomes, containing nearly complete repertoires of the plastid genes known in photosynthetic eukaryotes. Similarity analysis based on the whole plastid genome sequences showed the distance between <i>P</i>. <i>haitanensis</i> and <i>P</i>. <i>yezoensis</i> (0.146) was much smaller than that of <i>Porphyra purpurea</i> and <i>P</i>. <i>haitanensis</i> (0.250), and <i>P</i>. <i>yezoensis</i> (0.251); this supports re-grouping the two species in a resurrected genus <i>Pyropia</i> while maintaining <i>P. purpurea</i> in genus <i>Porphyra</i>. Phylogenetic analysis supports a sister relationship between Bangiophyceae and Florideophyceae, though precise phylogenetic relationships between multicellular red alage and chromists were not fully resolved.</p><p>Conclusions</p><p>These results indicate that <i>Pyropia</i> have compact plastid genomes. Large coding capacity and long intergenic regions contribute to the size of the largest plastid genomes reported for the red lineage. Possessing the largest coding capacity and ancient gene content yet found reveal that <i>Pyropia</i> are more primitive multicellular red algae.</p></div

Endocannabinoid dysfunction in neurological disease: neuro-ocular DAGLA-related syndrome

The endocannabinoid system is a highly conserved and ubiquitous signalling pathway with broad-ranging effects. Despite critical pathway functions, gene variants have not previously been conclusively linked to human disease. We identified nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All children displayed paroxysms of nystagmus or eye deviation accompanied by compensatory head posture and worsened incoordination most frequently after waking. RNA sequencing showed clear expression of the truncated transcript and no differences were found between mutant and wild-type DAGLA activity. Immunofluorescence staining of patient-derived fibroblasts and HEK cells expressing the mutant protein showed distinct perinuclear aggregation not detected in control samples. This report establishes truncating variants in the last DAGLA exon as the cause of a unique paediatric syndrome. Because enzymatic activity was preserved, the observed mislocalization of the truncated protein may account for the observed phenotype. Potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect. To our knowledge, this is the first report directly linking an endocannabinoid system component with human genetic disease and sets the stage for potential future therapeutic avenues