Phylogenomic Resolution of the Cetacean Tree of Life Using Target Sequence Capture.

The evolution of cetaceans, from their early transition to an aquatic lifestyle to their subsequent diversification, has been the subject of numerous studies. However, while the higher-level relationships among cetacean families have been largely settled, several aspects of the systematics within these groups remain unresolved. Problematic clades include the oceanic dolphins (37 spp.), which have experienced a recent rapid radiation, and the beaked whales (22 spp.), which have not been investigated in detail using nuclear loci. The combined application of high-throughput sequencing with techniques that target specific genomic sequences provide a powerful means of rapidly generating large volumes of orthologous sequence data for use in phylogenomic studies. To elucidate the phylogenetic relationships within the Cetacea, we combined sequence capture with Illumina sequencing to generate data for ∼3200 protein-coding genes for 68 cetacean species and their close relatives including the pygmy hippopotamus. By combining data from >38,000 exons with existing sequences from 11 cetaceans and seven outgroup taxa, we produced the first comprehensive comparative genomic dataset for cetaceans, spanning 6,527,596 aligned base pairs and 89 taxa. Phylogenetic trees reconstructed with maximum likelihood and Bayesian inference of concatenated loci, as well as with coalescence analyses of individual gene trees, produced mostly concordant and well-supported trees. Our results completely resolve the relationships among beaked whales as well as the contentious relationships among oceanic dolphins, especially the problematic subfamily Delphininae. We carried out Bayesian estimation of species divergence times using MCMCTree, and compared our complete dataset to a subset of clocklike genes. Analyses using the complete dataset consistently showed less variance in divergence times than the reduced dataset. In addition, integration of new fossils (e.g., Mystacodon selenensis) indicate that the diversification of Crown Cetacea began before the Late Eocene and the divergence of Crown Delphinidae as early as the Middle Miocene

Trypanosoma rangeli is phylogenetically closer to Old World trypanosomes than to Trypanosoma cruzi.

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Trypanosoma rangeli and Trypanosoma cruzi are generalist trypanosomes sharing a wide range of mammalian hosts; they are transmitted by triatomine bugs, and are the only trypanosomes infecting humans in the Neotropics. Their origins, phylogenetic relationships, and emergence as human parasites have long been subjects of interest. In the present study, taxon-rich analyses (20 trypanosome species from bats and terrestrial mammals) using ssrRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), heat shock protein-70 (HSP70) and Spliced Leader RNA sequences, and multilocus phylogenetic analyses using 11 single copy genes from 15 selected trypanosomes, provide increased resolution of relationships between species and clades, strongly supporting two main sister lineages: lineage Schizotrypanum, comprising T. cruzi and bat-restricted trypanosomes, and Tra[Tve-Tco] formed by T. rangeli, Trypanosoma vespertilionis and Trypanosoma conorhini clades. Tve comprises European T. vespertilionis and African T. vespertilionis-like of bats and bat cimicids characterised in the present study and Trypanosoma sp. Hoch reported in monkeys and herein detected in bats. Tco included the triatomine-transmitted tropicopolitan T. conorhini from rats and the African NanDoum1 trypanosome of civet (carnivore). Consistent with their very close relationships, Tra[Tve-Tco] species shared highly similar Spliced Leader RNA structures that were highly divergent from those of Schizotrypanum. In a plausible evolutionary scenario, a bat trypanosome transmitted by cimicids gave origin to the deeply rooted Tra[Tve-Tco] and Schizotrypanum lineages, and bat trypanosomes of diverse genetic backgrounds jumped to new hosts. A long and independent evolutionary history of T. rangeli more related to Old World trypanosomes from bats, rats, monkeys and civets than to Schizotrypanum spp., and the adaptation of these distantly related trypanosomes to different niches of shared mammals and vectors, is consistent with the marked differences in transmission routes, life-cycles and host-parasite interactions, resulting in T. cruzi (but not T. rangeli) being pathogenic to humans.This study was supported by grants awarded to MMGT and EPC from CNPq (National Council for Scientific and Technological Development) PROAFRICA, PROSUL and UNIVERSAL programs, CAPES (Coordination for the Improvement of Higher Education Personnel) PNIPB, PNPD and PROTAX programs, and FAPESP (São Paulo Research Foundation; process 2016/07487-0). Genome sequencing was supported by the Assembling the Tree of Life (ATOL) Project of the National Science Foundation, USA (NSF DEB-0830056), and TCC-USP (Trypanosomatid Culture Collection of the University of São Paulo) projects. OEA received PhD fellowships from CNPq (PROTAX) and COLCIENCIAS (Administrative Department of Science, Technology and Innovation, Colombia); PAO is a postdoctoral fellow of CAPES (PNPD); LL and AGCM are supported by a postdoctoral fellowship from CAPES (PROTAX)

Characterization and applications of a Crimean-Congo hemorrhagic fever virus nucleoprotein-specific Affimer: Inhibitory effects in viral replication and development of colorimetric diagnostic tests

Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) is one of the most widespread medically important arboviruses, causing human infections that result in mortality rates of up to 60%. We describe the selection of a high-affinity small protein (Affimer-NP) that binds specifically to the nucleoprotein (NP) of CCHFV. We demonstrate the interference of Affimer-NP in the RNA-binding function of CCHFV NP using fluorescence anisotropy, and its inhibitory effects on CCHFV gene expression in mammalian cells using a mini-genome system. Solution of the crystallographic structure of the complex formed by these two molecules at 2.84 Å resolution revealed the structural basis for this interference, with the Affimer-NP binding site positioned at the critical NP oligomerization interface. Finally, we validate the in vitro application of Affimer-NP for the development of enzyme-linked immunosorbent and lateral flow assays, presenting the first published point-of-care format test able to detect recombinant CCHFV NP in spiked human and animal sera

Localization of supersymmetric field theories on non-compact hyperbolic three-manifolds

We study supersymmetric gauge theories with an R-symmetry, defined on non-compact, hyperbolic, Riemannian three-manifolds, focusing on the case of a supersymmetry-preserving quotient of Euclidean AdS$_3$. We compute the exact partition function in these theories, using the method of localization, thus reducing the problem to the computation of one-loop determinants around a supersymmetric locus. We evaluate the one-loop determinants employing three different techniques: an index theorem, the method of pairing of eigenvalues, and the heat kernel method. Along the way, we discuss aspects of supersymmetry in manifolds with a conformal boundary, including supersymmetric actions and boundary conditions.Comment: v3:79p, minor clarifications and references adde

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

Spectral quantification of nonlinear behaviour of the nearshore seabed and correlations with potential forcings at Duck, N.C., U.S.A

Local bathymetric quasi-periodic patterns of oscillation are identified from monthly profile surveys taken at two shore-perpendicular transects at the USACE field research facility in Duck, North Carolina, USA, spanning 24.5 years and covering the swash and surf zones. The chosen transects are the two furthest (north and south) from the pier located at the study site. Research at Duck has traditionally focused on one or more of these transects as the effects of the pier are least at these locations. The patterns are identified using singular spectrum analysis (SSA). Possible correlations with potential forcing mechanisms are discussed by 1) doing an SSA with same parameter settings to independently identify the quasi-periodic cycles embedded within three potentially linked sequences: monthly wave heights (MWH), monthly mean water levels (MWL) and the large scale atmospheric index known as the North Atlantic Oscillation (NAO) and 2) comparing the patterns within MWH, MWL and NAO to the local bathymetric patterns. The results agree well with previous patterns identified using wavelets and confirm the highly nonstationary behaviour of beach levels at Duck; the discussion of potential correlations with hydrodynamic and atmospheric phenomena is a new contribution. The study is then extended to all measured bathymetric profiles, covering an area of 1100m (alongshore) by 440m (cross-shore), to 1) analyse linear correlations between the bathymetry and the potential forcings using multivariate empirical orthogonal functions (MEOF) and linear correlation analysis and 2) identify which collective quasi-periodic bathymetric patterns are correlated with those within MWH, MWL or NAO, based on a (nonlinear) multichannel singular spectrum analysis (MSSA). (...continued in submitted paper)Comment: 50 pages, 3 tables, 8 figure

Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that impairment of mitochondrial energy metabolism plays an important role in the pathophysiology of autism spectrum disorders (ASD; OMIM number: 209850). A significant proportion of ASD cases display biochemical alterations suggestive of mitochondrial dysfunction and several studies have reported that mutations in the mitochondrial DNA (mtDNA) molecule could be involved in the disease phenotype.</p> <p>Methods</p> <p>We analysed a cohort of 148 patients with idiopathic ASD for a number of mutations proposed in the literature as pathogenic in ASD. We also carried out a case control association study for the most common European haplogroups (hgs) and their diagnostic single nucleotide polymorphisms (SNPs) by comparing cases with 753 healthy and ethnically matched controls.</p> <p>Results</p> <p>We did not find statistical support for an association between mtDNA mutations or polymorphisms and ASD.</p> <p>Conclusions</p> <p>Our results are compatible with the idea that mtDNA mutations are not a relevant cause of ASD and the frequent observation of concomitant mitochondrial dysfunction and ASD could be due to nuclear factors influencing mitochondrion functions or to a more complex interplay between the nucleus and the mitochondrion/mtDNA.</p

Predictors for patient knowledge and reported behaviour regarding driving under the influence of medicines: a multi-country survey

<p>Abstract</p> <p>Background</p> <p>Reports on the state of knowledge about medicines and driving showed an increased concern about the role that the use of medicines might play in car crashes. Much of patient knowledge regarding medicines comes from communications with healthcare professionals. This study, part of the DRUID (Driving Under the Influence of Drugs, alcohol and medicines) project, was carried out in four European countries and attempts to define predictors for knowledge of patients who use driving-impairing medicines. The influence of socio-demographic variables on patient knowledge was investigated as well as the influence of socio-demographic factors, knowledge and attitudes on patients' reported behaviour regarding driving under the influence of medicines.</p> <p>Methods</p> <p>Pharmacists handed out questionnaires to patients who met the inclusion criteria: 1) prevalent user of benzodiazepines, antidepressants or first generation antihistamines for systemic use; 2) age between 18 and 75 years old and 3) actual driver of a motorised vehicle. Factors affecting knowledge and reported behaviour towards driving-impairing medicines were analysed by means of multiple linear regression analysis and multiple logistic regression analysis, respectively.</p> <p>Results</p> <p>A total of 633 questionnaires (out of 3.607 that were distributed to patients) were analysed. Patient knowledge regarding driving under the influence of medicines is better in younger and higher educated patients. Information provided to or accessed by patients does not influence knowledge. Patients who experienced side effects and who have a negative attitude towards driving under the influence of impairing medicines are more prone to change their driving frequency behaviour than those who use their motorised vehicles on a daily basis or those who use anti-allergic medicines.</p> <p>Conclusions</p> <p>Changes in driving behaviour can be predicted by negative attitudes towards driving under the influence of medicines but not by patients' knowledge regarding driving under the influence of medicines. Future research should not only focus on information campaigns for patients but also for healthcare providers as this might contribute to improve communications with patients regarding the risks of driving under the influence of medicines.</p

Effect of having private health insurance on the use of health care services: the case of Spain

Background: Several stakeholders have undertaken initiatives to propose solutions towards a more sustainable health system and Spain, as an example of a European country affected by austerity measures, is looking for ways to cut healthcare budgets. Methods: The aim of this paper is to study the effect of private health insurance on health care utilization using the latest micro-data from the European Community Household Panel (ECHP), the Spanish National Health Survey (SNHS) and the European Union Statistics on Income and Living Conditions (EU-SILC). We use matching techniques based on propensity score methods: single match, four matches, bias-adjustment and allowing for heteroskedasticity. Results: The results demonstrate that people with a private health insurance, use the public health system less than individuals without double health insurance coverage. Conclusions: Our conclusions are useful when policy makers design public-private partnership policie