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BACKGROUND Understanding the origins of genome content has long been a goal of molecular evolution and comparative genomics. By examining genome evolution through the guise of lineage-specific evolution, it is possible to make inferences about the evolutionary events that have given rise to species-specific diversification. Here we characterize the evolutionary trends found in chordate species using The Adaptive Evolution Database (TAED). TAED is a database of phylogenetically indexed gene families designed to detect episodes of directional or diversifying selection across chordates. Gene families within the database have been assessed for lineage-specific estimates of dN/dS and have been reconciled to the chordate species to identify retained duplicates. Gene families have also been mapped to the functional pathways and amino acid changes which occurred on high dN/dS lineages have been mapped to protein structures. RESULTS An analysis of this exhaustive database has enabled a characterization of the processelineage-specific evolution along the lineage leading to Cetacea through rapid sequence evolution in a duplicate gene with amino acid substitutions causing active site rearrangement. CONCLUSION Episodes of lineage-specific evolution are frequent throughout chordate species. Both duplication and directional selection have played large roles in the evolution of the phylum. TAED is a powerful tool for facilitating this understanding of lineage-specific evolution.BACKGROUND Modularity is the tendency for systems to organize into semi-independent units and can be a key to the evolution and diversification of complex biological systems. Snake venoms are highly variable modular systems that exhibit extreme diversification even across very short time scales. One well-studied venom phenotype dichotomy is a trade-off between neurotoxicity versus hemotoxicity that occurs through the high expression of a heterodimeric neurotoxic phospholipase A2 (PLA2) or snake venom metalloproteinases (SVMPs). We tested whether the variation in these venom phenotypes could occur via variation in regulatory sub-modules through comparative venom gland transcriptomics of representative Black-Speckled Palm-Pitvipers (Bothriechis nigroviridis) and Talamancan Palm-Pitvipers (B. nubestris). RESULTS We assembled 1517 coding sequences, including 43 toxins for B. nigroviridis and 1787 coding sequences including 42 toxins for B. nubestris. The venom gland transcriptomes were extremely divergent between of modularity in facilitating rapid evolution of complex traits.BACKGROUND With the rapid development of high-throughput sequencing technologies, many datasets on the same biological subject are generated. A meta-analysis is an approach that combines results from different studies on the same topic. The random-effects model in a meta-analysis enables the modeling of differences between studies by incorporating the between-study variance. RESULTS This paper proposes a moments estimator of the between-study variance that represents the across-study variation. A new random-effects method (DSLD2), which involves two-step estimation starting with the DSL estimate and the [Formula see text] in the second step, is presented. The DSLD2 method is compared with 6 other meta-analysis methods based on effect sizes across 8 aspects under three hypothesis settings. The results show that DSLD2 is a suitable method for identifying differentially expressed genes under the first hypothesis. The DSLD2 method is also applied to Alzheimer's microarray datasets. The differentially expressed genes detected by the DSLD2 method are significantly enriched in neurological diseases. CONCLUSIONS The results from both simulationes and an application show that DSLD2 is a suitable method for detecting differentially expressed genes under the first hypothesis.Pulmonary vein (PV) cardiomyocytes have the potential to generate spontaneous activity, in contrast to working myocytes of atria. Different electrophysiological properties underlie the potential automaticity of PV cardiomyocytes, one being the hyperpolarization-activated inward current (Ih), which facilitates the slow diastolic depolarization. In the present study, we examined pharmacological characteristics of the Ih of PV cardiomyocytes in rat, guinea pig and rabbit. The results showed that guinea pig and rat PV cardiomyocytes possessed sizeable amplitudes of the Ih, and the Ih of guinea pig was suppressed by Cs+, a blocker of the hyperpolarization-activated cation current. However, the Ih of rat was not suppressed by Cs+, but by Cd2+, a blocker of the Cl- current. The current density of the Ih of rabbit PV cardiomyocytes was significantly smaller than those of other species. This suggests that the ion channels that carry the Ih of PV cardiomyocytes differ among the animal species.OBJECTIVE Numerous genetic variants from meta-analyses of observational studies and GWAS were reported to be associated with migraine susceptibility. However, due to the random errors in meta-analyses, the noteworthiness of the results showing statistically significant remains doubtful. Thus, we performed this field synopsis and re-analysis study to evaluate the noteworthiness using a Bayesian approach in hope of finding true associations. METHODS Relevant meta-analyses from observational studies and GWAS examining correlation between all genetic variants and migraine risk were included in our study by a PubMed search. Identification of noteworthy associations were analyzed by false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP). Using noteworthy variants, GO enrichment analysis were conducted through DAVID online tool. Then, the PPI network and hub genes were performed using STRING database and CytoHubba software. RESULTS As for 8 significant genetic variants from observational studies, none of which showed noteworthy at prior probability of 0.001. Out of 47 significant genetic variants in GWAS, 36 were noteworthy at prior probability of 0.000001 via FPRP or BFDP. Nicotinamide We further found the pathways "positive regulation of cytosolic calcium ion concentration" and "inositol phosphate-mediated signaling" and hub genes including MEF2D, TSPAN2, PHACTR1, TRPM8 and PRDM16 related to migraine susceptibility. CONCLUSION Herein, we have identified several noteworthy variants for migraine susceptibility in this field synopsis. We hope these data would help identify novel genetic biomarkers and potential therapeutic target for migraine.
Read More: https://www.selleckchem.com/products/Nicotinamide(Niacinamide).html
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