Structural Relationships between Highly Conserved Elements and Genes in Vertebrate Genomes

Large numbers of sequence elements have been identified to be highly conserved among vertebrate genomes. These highly conserved elements (HCEs) are often located in or around genes that are involved in transcription regulation and early development. They have been shown to be involved in cis-regulatory activities through both in vivo and additional computational studies. We have investigated the structural relationships between such elements and genes in six vertebrate genomes human, mouse, rat, chicken, zebrafish and tetraodon and detected several thousand cases of conserved HCE-gene associations, and also cases of HCEs with no common target genes. A few examples underscore the potential significance of our findings about several individual genes. We found that the conserved association between HCE/HCEs and gene/genes are not restricted to elements by their absolute distance on the genome. Notably, long-range associations were identified and the molecular functions of the associated genes do not show any particular overrepresentation of the functional categories previously reported. HCEs in close proximity are found to be linked with different set of gene/genes. The results reflect the highly complex correlation between HCEs and their putative target genes

Phylogeny in Aid of the Present and Novel Microbial Lineages: Diversity in Bacillus

Bacillus represents microbes of high economic, medical and biodefense importance. Bacillus strain identification based on 16S rRNA sequence analyses is invariably limited to species level. Secondly, certain discrepancies exist in the segregation of Bacillus subtilis strains. In the RDP/NCBI databases, out of a total of 2611 individual 16S rDNA sequences belonging to the 175 different species of the genus Bacillus, only 1586 have been identified up to species level. 16S rRNA sequences of Bacillus anthracis (153 strains), B. cereus (211 strains), B. thuringiensis (108 strains), B. subtilis (271 strains), B. licheniformis (131 strains), B. pumilus (83 strains), B. megaterium (47 strains), B. sphaericus (42 strains), B. clausii (39 strains) and B. halodurans (36 strains) were considered for generating species-specific framework and probes as tools for their rapid identification. Phylogenetic segregation of 1121, 16S rDNA sequences of 10 different Bacillus species in to 89 clusters enabled us to develop a phylogenetic frame work of 34 representative sequences. Using this phylogenetic framework, 305 out of 1025, 16S rDNA sequences presently classified as Bacillus sp. could be identified up to species level. This identification was supported by 20 to 30 nucleotides long signature sequences and in silico restriction enzyme analysis specific to the 10 Bacillus species. This integrated approach resulted in identifying around 30% of Bacillus sp. up to species level and revealed that B. subtilis strains can be segregated into two phylogenetically distinct groups, such that one of them may be renamed

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Una serpiente boin gigante de un Paleoceno Neotropical revela temperaturas ecuatoriales más altas en el pasado

The largest extant snakes live in the tropics of South America and southeast Asia1,2,3 where high temperatures facilitate the evolution of large body sizes among air-breathing animals whose body temperatures are dependant on ambient environmental temperatures (poikilothermy)4,5. Very little is known about ancient tropical terrestrial ecosystems, limiting our understanding of the evolution of giant snakes and their relationship to climate in the past. Here we describe a boid snake from the oldest known neotropical rainforest fauna from the Cerrejón Formation (58–60 Myr ago) in northeastern Colombia. We estimate a body length of 13?m and a mass of 1,135?kg, making it the largest known snake6,7,8,9. The maximum size of poikilothermic animals at a given temperature is limited by metabolic rate4, and a snake of this size would require a minimum mean annual temperature of 30–34?°C to survive. This estimate is consistent with hypotheses of hot Palaeocene neotropics with high concentrations of atmospheric CO2 based on climate models10. Comparison of palaeotemperature estimates from the equator to those from South American mid-latitudes indicates a relatively steep temperature gradient during the early Palaeogene greenhouse, similar to that of today. Depositional environments and faunal composition of the Cerrejón Formation indicate an anaconda-like ecology for the giant snake, and an earliest Cenozoic origin of neotropical vertebrate faunas

A new dermatemydid (Testudines, Kinosternoidea) from the Paleocene-Eocene Thermal Maximum, Willwood Formation, southeastern Bighorn Basin, Wyoming

<div><p>ABSTRACT</p><p><i>Gomphochelys nanus</i>, new genus and species, is described from the earliest Wasatchian (biohorizon Wa 0; ∼55.8 Ma) of the southeastern Bighorn Basin, Washakie County, Wyoming. The new taxon represents the only known dermatemydid from the Paleocene–Eocene Thermal Maximum (PETM) interval and extends the lineage back from previous records by approximately 2 million years. <i>Gomphochelys nanus</i> has a thick tricarinate carapace and differs from other dermatemydids in attaining a smaller adult body size, having reduced plastral features, a posteriorly situated gular–humeral sulcus, an acarinate pygal, and thick shortened peripherals. Reexamination of previously described fossil dermatemydids suggests that the taxa <i>Baptemys tricarinata</i> and <i>Kallistira costilata</i> are junior synonyms of the middle–late Wasatchian <i>Notomorpha garmanii</i>, and <i>Baptemys fluviatilis</i> is likely a junior synonym of <i>Baptemys wyomingensis</i>. <i>Gomphochelys nanus</i> is a stem dermatemydid that is similar to <i>N. garmanii</i> but differs in possessing symplesiomorphies with the Late Cretaceous–Paleocene genera <i>Agomphus</i> and <i>Hoplochelys</i>. Aspects of shell morphology suggest that <i>G. nanus</i> was a commensurate swimmer and bottom-walker like extant <i>Dermatemys</i> and <i>Staurotypus</i>. The presence of a dermatemydid (a tropically distributed clade) in the southeastern Bighorn Basin during the PETM (when global temperatures increased by 5°C–10°C over a period of ∼60 ky) further supports the hypothesis that climate was megathermal in the region during this interval and is consistent with previously documented geographic range changes in both plants and animals. Dermatemydids disappear from the fossil record at the end of the PETM and don't reemerge until the next warming event, Eocene Thermal Maximum 2.</p><p>http://zoobank.org/urn:lsid:zoobank.org:pub:19A98079-5CAD-4BC5-8C21-2810AA576D98 </p><p>SUPPLEMENTAL DATA—Supplemental materials are available for this article for free at www.tandfonline.com/UJVP</p></div

Nuevas tortugas (Chelonia) desde el Eoceno tardío hasta el Mioceno tardío de la Cuenca del Canal de Panamá

Four distinct fossil turtle assemblages (Chelonia) are recognized from the Panama Canal Basin. The oldest, from the late Eocene–early Oligocene Gatuncillo Formation, is dominated by podocnemidid pleurodires. The early Miocene Culebra Formation includes both podocnemidids and trionychids. The early to middle Miocene Cucaracha Formation includes taxa classified in Geoemydidae (including Rhinoclemmys panamaensis n. sp.), Kinosternidae (represented by Staurotypus moschus n. sp.), large testudinids, trionychids, and podocnemidids, and finally, the late Miocene Gatun Formation records cheloniid sea turtles. These fossils include the oldest known representatives of Rhinoclemmys, the oldest record of kinosternids in Central America with a more extensive southern paleodistribution for Staurotypus and staurotypines in general, early occurrences of giant tortoises in the Neotropics, the oldest occurrence of soft-shell turtles in the tropics, the oldest late Eocene–early Oligocene Neotropical occurrences of podocnemidids. The Panamanian fossil turtles represent clades that are primarily endemic to North America, showing their very early arrival into the Neotropics prior to the complete emergence of the Isthmus of Panama, as well as their first contact with Caribbean-South American pleurodires by the early Miocene

A randomized controlled trial of social media interventions for risky drinking among adolescents and emerging adults

PurposeAlcohol use among adolescents and emerging adults is an important public health issue requiring prevention approaches. Herein, we describe outcomes from a randomized controlled trial testing the efficacy of group-based social media interventions targeting risky drinking among youth.ProceduresUsing social media advertisements to screen potential participants, we recruited 955 youth (ages 16-24) reporting recent risky drinking. After completing a baseline assessment, participants were randomized to 8-week secret Facebook group conditions: Social Media Intervention +&nbsp;Incentives for engagement, Social Media Intervention only, and attention-placebo control. Electronic coaches trained in motivational interviewing facilitated interaction in intervention groups. Primary outcomes include past 3-month alcohol use and consequences over 3-, 6-, and 12-month follow-ups. Secondary outcomes include other drug use, consequences, and impaired driving. We also measured intervention engagement and acceptability.ResultsThe interventions were well-received, with significantly greater acceptability ratings and engagement in the SMI+I condition relative to other groups. In adjusted analyses, there were no significant differences between interventions and control on alcohol-related outcomes, with all groups showing reductions. Regarding secondary outcomes (70.4% used other drugs), compared to control, the incentivized group reduced other drug use, consequences, and cannabis-impaired driving; the non-incentivized group did not significantly differ from the control condition.ConclusionsAmong this predominantly poly-substance using sample, findings were mixed, with significant effects of the incentivized social media intervention on drug (but not alcohol) outcomes. Future studies are needed to further refine social media-delivered interventions to reduce alcohol and other drug use.Trial registrationClinicalTrials.gov NCT02809586; University of Michigan HUM#00102242

Single-cell analysis of human adipose tissue identifies depot and disease specific cell types

The complex relationship between metabolic disease risk and body fat distribution in humans involves cellular characteristics which are specific to body fat compartments. Here we show depotspecific differences in the stromal vascual fraction of visceral and subcutaneous adipose tissue by performing single-cell RNA sequencing of tissue specimen from obese individuals. We characterize multiple immune cells, endothelial cells, fibroblasts, adipose and hematopoietic stem cell progenitors. Subpopulations of adipose-resident immune cells are metabolically active and associated with metabolic disease status and those include a population of potential dysfunctional CD8+ T cells expressing metallothioneins. We identify multiple types of adipocyte progenitors that are common across depots, including a subtype enriched in individuals with type 2 diabetes. Depot-specific analysis reveals a class of adipocyte progenitors unique to visceral adipose tissue, which shares common features with beige preadipocytes. Our human single-cell transcriptome atlas across fat depots provides a resource to dissect functional genomics of metabolic disease