Revision of Madagascar's Dwarf Lemurs (Cheirogaleidae:Cheirogaleus): Designation of Species, Candidate Species Status and Geographic Boundaries Based on Molecular and Morphological Data

The genus Cheirogaleus, the dwarf lemurs, is a radiation of strepsirrhine primates endemic to the island of Madagascar. The dwarf lemurs are taxonomically grouped in the family Cheirogaleidae (Infraorder: Lemuriformes) along with the genera Microcebus, Mirza, Allocebus, and Phaner. The taxonomic history of the genus Cheirogaleus has been controversial since its inception due to a paucity of evidence in support of some proposed species. In this study, we addressed this issue by expanding the geographic breadth of samples by 91 individuals and built upon existing mitochondrial (cytb and COII) and nuclear (FIBA and vWF) DNA datasets to better resolve the phylogeny of Cheirogaleus. The mitochondrial gene fragments D-loop and PAST as well as the CFTR-PAIRB nuclear loci were also sequenced. In agreement with previous genetic studies, numerous deep divergences were resolved in the C. major, C. minor and C. medius lineages. Four of these lineages were segregated as new species, seven were identified as confirmed candidate species, and four were designated as unconfirmed candidate species based on comparative mitochondrial DNA sequence data gleaned from the literature or this study. Additionally, C. thomasi was resurrected. Given the widespread distribution of the genus Cheirogaleus throughout Madagascar, the methodology employed in this study combined all available lines of evidence to standardize investigative procedures in a genus with limited access to type material and a lack of comprehensive sampling across its total distribution. Our results highlighted lineages that likely represent new species and identified localities that may harbor an as-yet undescribed cryptic species diversity pending further field and laboratory work.We are most grateful to the Ahmanson Foundation, the Theodore F. and Claire M. Hubbard Family Foundation, the Primate Action Fund / Conservation International, the Margot Marsh Biodiversity Foundation, and the National Geographic Society, for financial assistance

PhyloMarker—A Tool for Mining Phylogenetic Markers Through Genome Comparison: Application of the Mouse Lemur (Genus Microcebus) Phylogeny

Molecular phylogeny is a fundamental tool to understanding the evolution of all life forms. One common issue faced by molecular phylogeny is the lack of sufficient molecular markers. Here, we present PhyloMarker, a phylogenomic tool designed to find nuclear gene markers for the inference of phylogeny through multiple genome comparison. Around 800 candidate markers were identified by PhyloMarker through comparison of partial genomes of Microcebus and Otolemur. In experimental tests of 20 randomly selected markers, nine markers were successfully amplified by PCR and directly sequenced in all 17 nominal Microcebus species. Phylogenetic analyses of the sequence data obtained for 17 taxa and nine markers confirmed the distinct lineage inferred from previous mtDNA data. PhyloMarker has also been used by other projects including the herons (Ardeidae, Aves) phylogeny and the Wood mice (Muridae, Mammalia) phylogeny. All source code and sample data are made available at http://bioinfo-srv1.awh.unomaha.edu/phylomarker/

Injury Rates, Mechanisms, Risk Factors and Prevention Strategies in Youth Rugby Union: What’s All the Ruck-Us About? A Systematic Review and Meta-analysis

Background: Rugby Union is a collision team sport played globally. Despite this, significant concerns have been raised regarding the sport’s safety, particularly in youth players. Given this, a review of injury rates, risk factors and prevention strategies is required across different youth age groups as well as in males and females. Objective: The objective of this systematic review (SR) and meta-analysis was to investigate injury and concussion rates, risk factors and primary prevention strategies in youth rugby. Methods: To be included, studies were required to report either rates, risk factors or prevention strategies in youth rugby and to have a randomised controlled trial, quasi-experimental, cohort, case control, or ecological study design. Exclusion criteria included non-peer-reviewed grey literature, conference abstracts, case studies, previous systematic reviews and studies not written in English. Nine databases were searched. The full search strategy and list of sources are available and pre-registered on PROSPERO (Ref: CRD42020208343). Each study was assessed for risk of bias using the Downs and Black quality assessment tool. Meta-analyses were conducted using a DerSimonian Laird random effect model for each age group and sex. Results: Sixty-nine studies were included in this SR. The match injury rates (using a 24-h time-loss definition) were 40.2/1000 match hours (95% CI 13.9–66.5) in males and 69.0/1000 match hours (95% CI 46.8–91.2) in females. Concussion rates were 6.2/1000 player-hours (95% CI 5.0–7.4) for males and 33.9/1000 player-hours (95% CI: 24.1–43.7) for females. The most common injury site was lower extremity (males) and the head/neck (females). The most common injury type was ligament sprain (males) and concussion (females). The tackle was the most common event associated with injury in matches (55% male, 71% females). Median time loss was 21 days for males and 17 days for females. Twenty-three risk factors were reported. The risk factors with the strongest evidence were higher levels of play and increasing age. Primary injury prevention strategies were the focus of only eight studies and included law changes (n = 2), equipment (n = 4), education (n = 1) and training (n = 1). The prevention strategy with the most promising evidence was neuromuscular training. The primary limitations included a broad range of injury definitions (n = 9) and rate denominators (n = 11) used, as well as a limited number of studies which could be included in the meta-analysis for females (n = 2). Conclusion: A focus on high-quality risk factor and primary prevention evaluation should be considered in future studies. Targeting primary prevention and stakeholder education remain key strategies in the prevention, recognition and management of injuries and concussions in youth rugby

Injury Rates, Mechanisms, Risk Factors and Prevention Strategies in Youth Rugby Union: What’s All the Ruck-Us About? A Systematic Review and Meta-analysis

BackgroundRugby Union is a collision team sport played globally. Despite this, significant concerns have been raised regarding the sport’s safety, particularly in youth players. Given this, a review of injury rates, risk factors and prevention strategies is required across different youth age groups as well as in males and females.ObjectiveThe objective of this systematic review (SR) and meta-analysis was to investigate injury and concussion rates, risk factors and primary prevention strategies in youth rugby.MethodsTo be included, studies were required to report either rates, risk factors or prevention strategies in youth rugby and to have a randomised controlled trial, quasi-experimental, cohort, case control, or ecological study design. Exclusion criteria included non-peer-reviewed grey literature, conference abstracts, case studies, previous systematic reviews and studies not written in English. Nine databases were searched. The full search strategy and list of sources are available and pre-registered on PROSPERO (Ref: CRD42020208343). Each study was assessed for risk of bias using the Downs and Black quality assessment tool. Meta-analyses were conducted using a DerSimonian Laird random effect model for each age group and sex.ResultsSixty-nine studies were included in this SR. The match injury rates (using a 24-h time-loss definition) were 40.2/1000 match hours (95% CI 13.9–66.5) in males and 69.0/1000 match hours (95% CI 46.8–91.2) in females. Concussion rates were 6.2/1000 player-hours (95% CI 5.0–7.4) for males and 33.9/1000 player-hours (95% CI: 24.1–43.7) for females. The most common injury site was lower extremity (males) and the head/neck (females). The most common injury type was ligament sprain (males) and concussion (females). The tackle was the most common event associated with injury in matches (55% male, 71% females). Median time loss was 21 days for males and 17 days for females. Twenty-three risk factors were reported. The risk factors with the strongest evidence were higher levels of play and increasing age. Primary injury prevention strategies were the focus of only eight studies and included law changes (n = 2), equipment (n = 4), education (n = 1) and training (n = 1). The prevention strategy with the most promising evidence was neuromuscular training. The primary limitations included a broad range of injury definitions (n = 9) and rate denominators (n = 11) used, as well as a limited number of studies which could be included in the meta-analysis for females (n = 2).ConclusionA focus on high-quality risk factor and primary prevention evaluation should be considered in future studies. Targeting primary prevention and stakeholder education remain key strategies in the prevention, recognition and management of injuries and concussions in youth rugby

An Integrated Model of Multiple-Condition ChIP-Seq Data Reveals Predeterminants of Cdx2 Binding

Regulatory proteins can bind to different sets of genomic targets in various cell types or conditions. To reliably characterize such condition-specific regulatory binding we introduce MultiGPS, an integrated machine learning approach for the analysis of multiple related ChIP-seq experiments. MultiGPS is based on a generalized Expectation Maximization framework that shares information across multiple experiments for binding event discovery. We demonstrate that our framework enables the simultaneous modeling of sparse condition-specific binding changes, sequence dependence, and replicate-specific noise sources. MultiGPS encourages consistency in reported binding event locations across multiple-condition ChIP-seq datasets and provides accurate estimation of ChIP enrichment levels at each event. MultiGPS's multi-experiment modeling approach thus provides a reliable platform for detecting differential binding enrichment across experimental conditions. We demonstrate the advantages of MultiGPS with an analysis of Cdx2 binding in three distinct developmental contexts. By accurately characterizing condition-specific Cdx2 binding, MultiGPS enables novel insight into the mechanistic basis of Cdx2 site selectivity. Specifically, the condition-specific Cdx2 sites characterized by MultiGPS are highly associated with pre-existing genomic context, suggesting that such sites are pre-determined by cell-specific regulatory architecture. However, MultiGPS-defined condition-independent sites are not predicted by pre-existing regulatory signals, suggesting that Cdx2 can bind to a subset of locations regardless of genomic environment. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2–5.National Science Foundation (U.S.) (Graduate Research Fellowship under Grant 0645960)National Institutes of Health (U.S.) (grant P01 NS055923)Pennsylvania State University. Center for Eukaryotic Gene Regulatio

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN