A computational reconstruction of Papio phylogeny using Alu insertion polymorphisms

© 2018 The Author(s). Background: Since the completion of the human genome project, the diversity of genome sequencing data produced for non-human primates has increased exponentially. Papio baboons are well-established biological models for studying human biology and evolution. Despite substantial interest in the evolution of Papio, the systematics of these species has been widely debated, and the evolutionary history of Papio diversity is not fully understood. Alu elements are primate-specific transposable elements with a well-documented mutation/insertion mechanism and the capacity for resolving controversial phylogenetic relationships. In this study, we conducted a whole genome analysis of Alu insertion polymorphisms unique to the Papio lineage. To complete these analyses, we created a computational algorithm to identify novel Alu insertions in next-generation sequencing data. Results: We identified 187,379 Alu insertions present in the Papio lineage, yet absent from M. mulatta [Mmul8.0.1]. These elements were characterized using genomic data sequenced from a panel of twelve Papio baboons: two from each of the six extant Papio species. These data were used to construct a whole genome Alu-based phylogeny of Papio baboons. The resulting cladogram fully-resolved relationships within Papio. Conclusions: These data represent the most comprehensive Alu-based phylogenetic reconstruction reported to date. In addition, this study produces the first fully resolved Alu-based phylogeny of Papio baboons

Gas-Phase Ambient Air Contaminants Exhibit Significant Dioxin-like and Estrogen-like Activity in Vitro

Several adverse health effects, such as respiratory and cardiovascular morbidity, have been linked to exposure to particulate matter in ambient air; however, the biologic activity of gas-phase ambient organic air contaminants has not been examined as thoroughly. Using aryl hydrocarbon receptor (AHR)–based and estrogen receptor (ER)–based cell bioassay systems, we assessed the dioxin-like and estrogenic activities of gas-phase organic ambient air contaminants compared with those of particulate-phase contaminants using samples collected between seasons over 2 years from an urban and a rural location in the Greater Toronto Area, Canada. The concentration of the sum (∑) of polycyclic aromatic hydrocarbons, which was highest in the gas phase, was 10–100 times more abundant than that of ∑polychlorinated biphenyls, ∑nitro-polycyclic aromatic hydrocarbons, and ∑organochlorine pesticides, and 10(3) to 10(4) times more abundant than ∑polychlorinated dibenzo-p-dioxins/dibenzofurans. Gas-phase samples induced significant AHR- and ER-dependent gene expression. The activity of the gas-phase samples was greater than that of the particulate-phase samples in the estrogen assay and, in one case, in the AHR assay. We found no strong associations between either summer or winter seasons or urban or rural locations in the relative efficacy of the extracts in either the ER or AHR assay despite differences in chemical composition, concentrations, and abundance. Our results suggest that mechanistic studies of the health effects of ambient air must consider gas and particulate phases because chemicals present in both phases can affect AHR and ER signaling pathways

Analysis of lineage-specific Alu subfamilies in the genome of the olive baboon, Papio anubis

© 2018 The Author(s). Background: Alu elements are primate-specific retroposons that mobilize using the enzymatic machinery of L1 s. The recently completed baboon genome project found that the mobilization rate of Alu elements is higher than in the genome of any other primate studied thus far. However, the Alu subfamily structure present in and specific to baboons had not been examined yet. Results: Here we report 129 Alu subfamilies that are propagating in the genome of the olive baboon, with 127 of these subfamilies being new and specific to the baboon lineage. We analyzed 233 Alu insertions in the genome of the olive baboon using locus specific polymerase chain reaction assays, covering 113 of the 129 subfamilies. The allele frequency data from these insertions show that none of the nine groups of subfamilies are nearing fixation in the lineage. Conclusions: Many subfamilies of Alu elements are actively mobilizing throughout the baboon lineage, with most being specific to the baboon lineage

Papio baboon species indicative Alu elements

© The Author(s) 2017. The genus of Papio (baboon) has six recognized species separated into Northern and Southern clades, each comprised of three species distributed across the African continent. Geographic origin and phenotypic variants such as coat color and body size have commonly been used to identify different species. The existence ofmultiple hybrid zones, both ancient and current, have complicated efforts to characterize the phylogeny of Papio baboons. More recently, mitochondrial DNA (mtDNA) and Y-chromosome genetic markers have been utilized for species identification with particular focus on the hybrid zones. Alu elements accumulate in a random manner and are a novel source of identical by descent variation with known ancestral states for inferring population genetic and phylogenetic relationships. As part of the Baboon Genome Analysis Consortium, we assembled an Alu insertion polymorphism database of nearly 500 Papio-lineage specific insertions representing all six species and performed population structure and phylogenetic analyses. In this study, we have selected a subset of 48 species indicative Alu insertions and demonstrate their utility as genetic systems for the identification of baboon species within Papio. Individual elements from the panel are easy to genotype and can be used in a hierarchical fashion based on the original level of uncertainty. This Alu-48 panel should serve as a valuable tool during the maintenance of pedigree records in captive populations and assist in the forensic identification of fossils and potential hybrids in the wild

The feasibility of a randomised controlled trial to compare the cost-effectiveness of palliative cardiology or usual care in people with advanced heart failure: Two exploratory prospective cohorts

© 2018, © The Author(s) 2018. Background: The effectiveness of cardiology-led palliative care is unknown; we have insufficient information to conduct a full trial. Aim: To assess the feasibility (recruitment/retention, data quality, variability/sample size estimation, safety) of a clinical trial of palliative cardiology effectiveness. Design: Non-randomised feasibility. Setting/participants: Unmatched symptomatic heart failure patients on optimal cardiac treatment from (1) cardiology-led palliative service (caring together group) and (2) heart failure liaison service (usual care group). Outcomes/safety: Symptoms (Edmonton Symptom Assessment Scale), Kansas City Cardiomyopathy Questionnaire, performance, understanding of disease, anticipatory care planning, cost-effectiveness, survival and carer burden. Results: A total of 77 participants (caring together group = 43; usual care group = 34) were enrolled (53% men; mean age 77 years (33–100)). The caring together group scored worse in Edmonton Symptom Assessment Scale (43.5 vs 35.2) and Kansas City Cardiomyopathy Questionnaire (35.4 vs 39.9). The caring together group had a lower consent/screen ratio (1:1.7 vs 1: 2.8) and few died before approach (0.08% vs 16%) or declined invitation (17% vs 37%). Data quality: At 4 months, 74% in the caring together group and 71% in the usual care group provided data. Most attrition was due to death or deterioration. Data quality in self-report measures was otherwise good. Safety: There was no difference in survival. Symptoms and quality of life improved in both groups. A future trial requires 141 (202 allowing 30% attrition) to detect a minimal clinical difference (1 point) in Edmonton Symptom Assessment Scale score for breathlessness (80% power). More participants (176; 252 allowing 30% attrition) are needed to detect a 10.5 change in Kansas City Cardiomyopathy Questionnaire score (80% power; minimum clinical difference = 5). Conclusion: A trial to test the clinical effectiveness (improvement in breathlessness) of cardiology-led palliative care is feasible

Alu insertion polymorphisms shared by Papio baboons and Theropithecus gelada reveal an intertwined common ancestry

© 2019 The Author(s). Background: Baboons (genus Papio) and geladas (Theropithecus gelada) are now generally recognized as close phylogenetic relatives, though morphologically quite distinct and generally classified in separate genera. Primate specific Alu retrotransposons are well-established genomic markers for the study of phylogenetic and population genetic relationships. We previously reported a computational reconstruction of Papio phylogeny using large-scale whole genome sequence (WGS) analysis of Alu insertion polymorphisms. Recently, high coverage WGS was generated for Theropithecus gelada. The objective of this study was to apply the high-Throughput poly-Detect method to computationally determine the number of Alu insertion polymorphisms shared by T. gelada and Papio, and vice versa, by each individual Papio species and T. gelada. Secondly, we performed locus-specific polymerase chain reaction (PCR) assays on a diverse DNA panel to complement the computational data. Results: We identified 27,700 Alu insertions from T. gelada WGS that were also present among six Papio species, with nearly half (12,956) remaining unfixed among 12 Papio individuals. Similarly, each of the six Papio species had species-indicative Alu insertions that were also present in T. gelada. In general, P. kindae shared more insertion polymorphisms with T. gelada than did any of the other five Papio species. PCR-based genotype data provided additional support for the computational findings. Conclusions: Our discovery that several thousand Alu insertion polymorphisms are shared by T. gelada and Papio baboons suggests a much more permeable reproductive barrier between the two genera then previously suspected. Their intertwined evolution likely involves a long history of admixture, gene flow and incomplete lineage sorting

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Inositol 1,4,5-Trisphosphate Signalling Regulates the Avoidance Response to Nose Touch in Caenorhabditis elegans

When Caenorhabditis elegans encounters an unfavourable stimulus at its anterior, it responds by initiating an avoidance response, namely reversal of locomotion. The amphid neurons, ASHL and ASHR, are polymodal in function, with roles in the avoidance responses to high osmolarity, nose touch, and both volatile and non-volatile repellents. The mechanisms that underlie the ability of the ASH neurons to respond to such a wide range of stimuli are still unclear. We demonstrate that the inositol 1,4,5-trisphosphate receptor (IP3R), encoded by itr-1, functions in the reversal responses to nose touch and benzaldehyde, but not in other known ASH-mediated responses. We show that phospholipase Cβ (EGL-8) and phospholipase Cγ (PLC-3), which catalyse the production of IP3, both function upstream of ITR-1 in the response to nose touch. We use neuron-specific gene rescue and neuron-specific disruption of protein function to show that the site of ITR-1 function is the ASH neurons. By rescuing plc-3 and egl-8 in a neuron-specific manner, we show that both are acting in ASH. Imaging of nose touch–induced Ca2+ transients in ASH confirms these conclusions. In contrast, the response to benzaldehyde is independent of PLC function. Thus, we have identified distinct roles for the IP3R in two specific responses mediated by ASH

Global and Local Features of Semantic Networks: Evidence from the Hebrew Mental Lexicon

BACKGROUND: Semantic memory has generated much research. As such, the majority of investigations have focused on the English language, and much less on other languages, such as Hebrew. Furthermore, little research has been done on search processes within the semantic network, even though they are abundant within cognitive semantic phenomena. METHODOLOGY/PRINCIPAL FINDINGS: We examine a unique dataset of free association norms to a set of target words and make use of correlation and network theory methodologies to investigate the global and local features of the Hebrew lexicon. The global features of the lexicon are investigated through the use of association correlations--correlations between target words, based on their association responses similarity; the local features of the lexicon are investigated through the use of association dependencies--the influence words have in the network on other words. CONCLUSIONS/SIGNIFICANCE: Our investigation uncovered Small-World Network features of the Hebrew lexicon, specifically a high clustering coefficient and a scale-free distribution, and provides means to examine how words group together into semantically related 'free categories'. Our novel approach enables us to identify how words facilitate or inhibit the spread of activation within the network, and how these words influence each other. We discuss how these properties relate to classical research on spreading activation and suggest that these properties influence cognitive semantic search processes. A semantic search task, the Remote Association Test is discussed in light of our findings