A genetic linkage map of the hermaphrodite teleost fish Sparus aurata L.

The gilthead sea bream (Sparus aurata L.) is a marine fish of great importance for fisheries and aquaculture. It has also a peculiar sex-determination system, being a protandrous hermaphrodite. Here we report the construction of a first-generation genetic linkage map for S. aurata, based on 204 microsatellite markers. Twenty-six linkage groups (LG) were found. The total map length was 1241.9 cM. The ratio between sex-specific map lengths was 1:1.2 (male:female). Comparison with a preliminary radiation hybrid (RH) map reveals a good concordance, as all markers located in a single LG are located in a single RH group, except for Ad-25 and CId-31. Comparison with the Tetraodon nigroviridis genome revealed a considerable number of evolutionary conserved regions (ECRs) between the two species. The mean size of ECRs was 182 bp (sequence identity 60–90%). Forty-one ECRs have a known chromosomal location in the pufferfish genome. Despite the limited number of anchoring points, significant syntenic relationships were found. The linkage map presented here provides a robust comparative framework for QTL analysis in S. aurata and is a step toward the identification of genetic loci involved both in the determination of economically important traits and in the individual timing of sex reversal

The natural science of cosmology

The network of cosmological tests is tight enough now to show that the relativistic Big Bang cosmology is a good approximation to what happened as the universe expanded and cooled through light element production and evolved to the present. I explain why I reach this conclusion, comment on the varieties of philosophies informing searches for a still better cosmology, and offer an example for further study, the curious tendency of some classes of galaxies to behave as island universes.Comment: Keynote lecture at the seventh International Conference on Gravitation and Cosmology, Goa India, December 201

The 6dF galaxy survey: fundamental plane data

We report the 6dFGS Fundamental Plane (6dFGSv) catalogue that is used to estimate distances and peculiar velocities for nearly 9000 early-type galaxies in the local (z < 0.055) universe. Velocity dispersions are derived by cross-correlation from 6dF V-band spectra with typical S/N of 12.9 Å−1 for a sample of 11 315 galaxies; the median velocity dispersion is 163 km s−1 and the median measurement error is 12.9 per cent. The photometric Fundamental Plane (FP) parameters (effective radii and surface brightnesses) are determined from the JHK 2MASS images for 11 102 galaxies. Comparison of the independent J- and K-band measurements implies that the average uncertainty in XFP, the combined photometric parameter that enters the FP, is 0.013 dex (3 per cent) for each band. Visual classification of morphologies was used to select a sample of nearly 9000 early-type galaxies that form 6dFGSv. This catalogue has been used to study the effects of stellar populations on galaxy scaling relations, to investigate the variation of the FP with environment and galaxy morphology, to explore trends in stellar populations through, along and across the FP, and to map and analyse the local peculiar velocity field

Wandering behaviour prevents inter and intra oceanic speciation in a coastal pelagic fish

Small pelagic fishes have the ability to disperse over long distances and may present complex evolutionary histories. Here, Old World Anchovies (OWA) were used as a model system to understand genetic patterns and connectivity of fish between the Atlantic and Pacific basins. We surveyed 16 locations worldwide using mtDNA and 8 microsatellite loci for genetic parameters, and mtDNA (cyt b; 16S) and nuclear (RAG1; RAG2) regions for dating major lineage-splitting events within Engraulidae family. The OWA genetic divergences (0-0.4%) are compatible with intra-specific divergence, showing evidence of both ancient and contemporary admixture between the Pacific and Atlantic populations, enhanced by high asymmetrical migration from the Pacific to the Atlantic. The estimated divergence between Atlantic and Pacific anchovies (0.67 [0.53-0.80] Ma) matches a severe drop of sea temperature during the Gunz glacial stage of the Pleistocene. Our results support an alternative evolutionary scenario for the OWA, suggesting a coastal migration along south Asia, Middle East and eastern Africa continental platforms, followed by the colonization of the Atlantic via the Cape of the Good Hope.Portuguese Foundation for Science & Technology (FCT) [SFRH/BD/36600/2007]; FCT [UID/MAR/04292/2013, SFRH/BPD/65830/2009]; FCT strategic plan [UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

Design, synthesis and antiparasitic evaluation of click phospholipids

A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against Leishmania infantum and Leishmania donovani intracellular amastigotes, against Trypanosoma brucei brucei and against different developmental stages of Trypanosoma cruzi. The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure\u2013activity relationships. The early ADMET profile of the new derivatives did not reveal major liabilities for the potent compounds. The 1,2,3-triazole derivative 27 substituted by a decyl tail, an undecyl spacer and a choline head group exhibited broad spectrum antiparasitic activity. It possessed low micromolar activity against the intracellular amastigotes of two L. infantum strains and T. cruzi Y strain epimastigotes, intracellular amastigotes and trypomastigotes, while its cytotoxicity concentration (CC50) against THP-1 macrophages ranged between 50 and 100 \ub5M. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases

De novo deletions and duplications of 17q25.3 cause susceptibility to cardiovascular malformations

BACKGROUND: Genomic disorders resulting from deletion or duplication of genomic segments are known to be an important cause of cardiovascular malformations (CVMs). In our previous study, we identified a unique individual with a de novo 17q25.3 deletion from a study of 714 individuals with CVM. METHODS: To understand the contribution of this locus to cardiac malformations, we reviewed the data on 60,000 samples submitted for array comparative genomic hybridization (CGH) studies to Medical Genetics Laboratories at Baylor College of Medicine, and ascertained seven individuals with segmental aneusomy of 17q25. We validated our findings by studying another individual with a de novo submicroscopic deletion of this region from Cytogenetics Laboratory at Cincinnati Children's Hospital. Using bioinformatic analyses including protein-protein interaction network, human tissue expression patterns, haploinsufficiency scores, and other annotation systems, including a training set of 251 genes known to be linked to human cardiac disease, we constructed a pathogenicity score for cardiac phenotype for each of the 57 genes within the terminal 2.0 Mb of 17q25.3. RESULTS: We found relatively high penetrance of cardiovascular defects (~60 %) with five deletions and three duplications, observed in eight unrelated individuals. Distinct cardiac phenotypes were present in four of these subjects with non-recurrent de novo deletions (range 0.08 Mb-1.4 Mb) in the subtelomeric region of 17q25.3. These included coarctation of the aorta (CoA), total anomalous pulmonary venous return (TAPVR), ventricular septal defect (VSD) and atrial septal defect (ASD). Amongst the three individuals with variable size duplications of this region, one had patent ductus arteriosus (PDA) at 8 months of age. CONCLUSION: The distinct cardiac lesions observed in the affected patients and the bioinformatics analyses suggest that multiple genes may be plausible drivers of the cardiac phenotype within this gene-rich critical interval of 17q25.3

A gene-based radiation hybrid map of the gilthead sea bream Sparus aurata refines and exploits conserved synteny with Tetraodon nigroviridis

Background: Comparative teleost studies are of great interest since they are important in aquaculture and in evolutionary issues. Comparing genomes of fully sequenced model fish species with those of farmed fish species through comparative mapping offers shortcuts for quantitative trait loci (QTL) detections and for studying genome evolution through the identification of regions of conserved synteny in teleosts. Here a comparative mapping study is presented by radiation hybrid (RH) mapping genes of the gilthead sea bream Sparus aurata, a non-model teleost fish of commercial and evolutionary interest, as it represents the worldwide distributed species-rich family of Sparidae.Results: An additional 74 microsatellite markers and 428 gene-based markers appropriate for comparative mapping studies were mapped on the existing RH map of Sparus aurata. The anchoring of the RH map to the genetic linkage map resulted in 24 groups matching the karyotype of Sparus aurata. Homologous sequences to Tetraodon were identified for 301 of the gene-based markers positioned on the RH map of Sparus aurata. Comparison between Sparus aurata RH groups and Tetraodon chromosomes (karyotype of Tetraodon consists of 21 chromosomes) in this study reveals an unambiguous one-to-one relationship suggesting that three Tetraodon chromosomes correspond to six Sparus aurata radiation hybrid groups. The exploitation of this conserved synteny relationship is furthermore demonstrated by in silico mapping of gilthead sea bream expressed sequence tags (EST) that give a significant similarity hit to Tetraodon.Conclusion: The addition of primarily gene-based markers increased substantially the density of the existing RH map and facilitated comparative analysis. The anchoring of this gene-based radiation hybrid map to the genome maps of model species broadened the pool of candidate genes that mainly control growth, disease resistance, sex determination and reversal, reproduction as well as environmental tolerance in this species, all traits of great importance for QTL mapping and marker assisted selection. Furthermore this comparative mapping approach will facilitate to give insights into chromosome evolution and into the genetic make up of the gilthead sea bream

The cloudUPDRS app: a medical device for the clinical assessment of Parkinson's Disease

Parkinson's Disease is a neurological condition distinguished by characteristic motor symptoms including tremor and slowness of movement. To enable the frequent assessment of PD patients, this paper introduces the cloudUPDRS app, a Class I medical device that is an active transient non-invasive instrument, certified by the Medicines and Healthcare products Regulatory Agency in the UK. The app follows closely Part III of the Unified Parkinson's Disease Rating Scale which is the most commonly used protocol in the clinical study of PD; can be used by patients and their carers at home or in the community unsupervised; and, requires the user to perform a sequence of iterated movements which are recorded by the phone sensors. The cloudUPDRS system addresses two key challenges towards meeting essential consistency and efficiency requirements, namely: (i) How to ensure high-quality data collection especially considering the unsupervised nature of the test, in particular, how to achieve firm user adherence to the prescribed movements; and (ii) How to reduce test duration from approximately 25 minutes typically required by an experienced patient, to below 4 minutes, a threshold identified as critical to obtain significant improvements in clinical compliance. To address the former, we combine a bespoke design of the user experience tailored so as to constrain context, with a deep learning approach based on Recurrent Convolutional Neural Networks, to identify failures to follow the movement protocol. We address the latter by developing a machine learning approach to personalize assessments by selecting those elements of the test that most closely match individual symptom profiles and thus offer the highest inferential power, hence closely estimating the patent's overall score

Customised ensemble methodologies for deep learning: boosted residual networks and related approaches

This paper introduces a family of new customised methodologies for ensembles, called Boosted Residual Networks (BRN), which builds a boosted ensemble of Residual Networks by growing the member network at each round of boosting. The proposed approach combines recent developements in Residual Networks - a method for creating very deep networks by including a shortcut layer between different groups of layers - with Deep Incremental Boosting, a methodology to train fast ensembles of networks of increasing depth through the use of boosting. Additionally, we explore a simpler variant of Boosted Residual Networks based on Bagging, called Bagged Residual Networks (BaRN). We then analyse how the recent developments in Ensemble distillation can improve our results.We demonstrate that the synergy of Residual Networks and Deep Incremental Boosting has better potential than simply boosting a Residual Network of fixed structure or using the equivalent Deep Incremental Boosting without the shortcut layers, by permitting the creation of models with better generalisation in significantly less time

The sixth international RASopathies symposium: Precision medicine—From promise to practice

The RASopathies are a group of genetic disorders that result from germline pathogenic variants affecting RAS‐mitogen activated protein kinase (MAPK) pathway genes. RASopathies share RAS/MAPK pathway dysregulation and share phenotypic manifestations affecting numerous organ systems, causing lifelong and at times life‐limiting medical complications. RASopathies may benefit from precision medicine approaches. For this reason, the Sixth International RASopathies Symposium focused on exploring precision medicine. This meeting brought together basic science researchers, clinicians, clinician scientists, patient advocates, and representatives from pharmaceutical companies and the National Institutes of Health. Novel RASopathy genes, variants, and animal models were discussed in the context of medication trials and drug development. Attempts to define and measure meaningful endpoints for treatment trials were discussed, as was drug availability to patients after trial completion