Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia.

BackgroundTwo congenital bleeding diatheses have been identified in Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis associated with abnormal platelet function in response to collagen and thrombin stimulation.Hypothesis/objectivesPlatelet dysfunction in horses with this second thrombasthenia results from a secretory defect.AnimalsTwo affected and 6 clinically normal horses.MethodsEx vivo study. Washed platelets were examined for (1) expression of the αIIb-β3 integrin; (2) fibrinogen binding capacity in response to ADP and thrombin; (3) secretion of dense and α-granules; (4) activation of the mammalian target of rapamycin (mTOR)-protein kinase B (AKT) signaling pathway; and (5) cellular distribution of phosphatidylinositol-4-phosphate-3-kinase, class 2B (PIK3C2B) and SH2 containing inositol-5'-phosphatase 1 (SHIP1).ResultsPlatelets from affected horses expressed normal amounts of αIIb-β3 integrin and bound fibrinogen normally in response to ADP, but bound 80% less fibrinogen in response to thrombin. α-granules only released 50% as much Factor V as control platelets, but dense granules released their contents normally. Protein kinase B (AKT) phosphorylation was reduced after thrombin activation, but mTOR Complex 2 (mTORC2) and phosphoinositide-dependent kinase 1 (PDK1) signaling were normal. SH2-containing inositol-5'-phosphatase 1 (SHIP1) did not localize to the cytoskeleton of affected platelets and was decreased overall consistent with reduced AKT phosphorylation.Conclusions and clinical significanceDefects in fibrinogen binding, granule secretion, and signal transduction are unique to this thrombasthenia, which we designate as atypical equine thrombasthenia

HeteroGenius: A Framework for Hybrid Analysis of Heterogeneous Software Specifications

Nowadays, software artifacts are ubiquitous in our lives being an essential part of home appliances, cars, cell phones, and even in more critical activities like aeronautics and health sciences. In this context software failures may produce enormous losses, either economical or, in the worst case, in human lives. Software analysis is an area in software engineering concerned with the application of diverse techniques in order to prove the absence of errors in software pieces. In many cases different analysis techniques are applied by following specific methodological combinations that ensure better results. These interactions between tools are usually carried out at the user level and it is not supported by the tools. In this work we present HeteroGenius, a framework conceived to develop tools that allow users to perform hybrid analysis of heterogeneous software specifications. HeteroGenius was designed prioritising the possibility of adding new specification languages and analysis tools and enabling a synergic relation of the techniques under a graphical interface satisfying several well-known usability enhancement criteria. As a case-study we implemented the functionality of Dynamite on top of HeteroGenius.Comment: In Proceedings LAFM 2013, arXiv:1401.056

MoCheQoS: Automated Analysis of Quality of Service Properties of Communicating Systems

We present MoCheQoS, a tool to analyse quality of service (QoS) properties of message-passing systems. Building on the logic and the choreographic model we defined in recently published work, MoCheQoS implements a bounded model checking algorithm. We discuss strengths and weaknesses of MoCheQoS through some case studies.Comment: 29 page

Bionomics and taxonomy of leafhopper Sophonia orientalis (Homoptera: Cicadellidae), a Pacific pest species in the Macaronesian Archipelagos

The leafhopper Sophonia orientalis (Matsumura) (Homoptera: Cicadellidae) is native to Asia, but it has been recently introduced to the Hawaii Archipelago, CA and French Polynesia. Although this extremely polyphagous species is considered to be a threat to all native plants of Hawaii and to many economically important cropping cultures, its taxonomy remains obscure. Most literature referred to this species as Sophonia rufofascia (Kuoh & Kuoh), but recently it has been shown that previous records of this species correspond to S. orientalis. In this study, S. orientalis is recorded from northeastern Atlantic archipelagos of Madeira and Canaries, with the Þrst collection made in 2000 representing the Þrst record of this species for Macaronesia. Diagnosis of the species together with information on the karyotype and structure of testes and ovaries is given. The number of chromosomes is 2n 16 X0 (males) and 2n 16 XX (females), and each testis and ovaryis composed of six follicles and six ovarioles, respectively. In Madeira, S. orientalis was found on 28 plant species, including native and endemic plants, but it also was associated with important crops such as vineyards. The presence of adults and nymphs during most of the year suggests that this species has several annual generations. Owing to the suitable climate and the presence of a great number of host plants, its potential for detrimental effects to Madeira ecosystems is considered to be great, and the proximity of Madeira and Canary Islands to the European land mass suggests that this pest may spread.info:eu-repo/semantics/publishedVersio

On the construction of explosive relation algebras

Fork algebras are an extension of relation algebras obtained by extending the set of logical symbols with a binary operator called fork. This class of algebras was introduced by Haeberer and Veloso in the early 90's aiming at enriching relation algebra, an already successful language for program specification, with the capability of expressing some form of parallel computation. The further study of this class of algebras led to many meaningful results linked to interesting properties of relation algebras such as representability and finite axiomatizability, among others. Also in the 90's, Veloso introduced a subclass of relation algebras that are expansible to fork algebras, admitting a large number of non-isomorphic expansions, referred to as explosive relation algebras. In this work we discuss some general techniques for constructing algebras of this type

Evidence for TTAGG telomere repeats and rRNA gene clusters in leafhoppers of the genus Alebra (Hemiptera: Auchenorrhyncha: Cicadellidae)

The leafhopper genus Alebra Fieber, 1872 comprises a complex of morphologically similar species. The chromosome complements (karyotypes) of five Alebra species, i.e. A. albostriella, A. coryli, A. viridis, A. wahlbergi and a new, yet undescribed species, provisionally named Taxon 1, were here investigated, three of these species (A. coryli, A. viridis, and Taxon 1) for the first time. The techniques applied included standard chromosome staining, fluorescence in situ hybridization (FISH) for mapping of 18S rDNA and telomeric repeats (in every species), C-banding, AgNOR-banding and CMA3 /DAPI- staining (in A. viridis). The species have a holokinetic type of chromosomes, as in other hemipterans. Karyotypes of all species are remarkably conserved with 2n = 22 + X(0)/XX (male/female), one large and 10 medium pairs of autosomes and the X chromosome similar in size to larger chromosomes within this group. In every species, FISH identified the “classical” insect telomere repeat of TTAGG and rRNA gene clusters located on the homologues of a medium-sized pair of autosomes, presumably number 5. Thus, speciation in Alebra has apparently not involved significant karyotypic changes. In A. viridis, rDNA sites were both Ag- and CMA3 -positive and were located at an interstitial position. C-banding revealed heterochromatic bands in the X chromosome and also in all but four pairs of autosomes, the bands were located at one telomere of a chromosome. C-bands were positive for CMA3 and negative for DAPI, suggesting that C-heterochromatin is mainly enriched in GC-pairs.info:eu-repo/semantics/publishedVersio

Equitable modelling of brain imaging by counterfactual augmentation with morphologically constrained 3D deep generative models

We describe CounterSynth, a conditional generative model of diffeomorphic deformations that induce label-driven, biologically plausible changes in volumetric brain images. The model is intended to synthesise counterfactual training data augmentations for downstream discriminative modelling tasks where fidelity is limited by data imbalance, distributional instability, confounding, or underspecification, and exhibits inequitable performance across distinct subpopulations. Focusing on demographic attributes, we evaluate the quality of synthesised counterfactuals with voxel-based morphometry, classification and regression of the conditioning attributes, and the Fréchet inception distance. Examining downstream discriminative performance in the context of engineered demographic imbalance and confounding, we use UK Biobank and OASIS magnetic resonance imaging data to benchmark CounterSynth augmentation against current solutions to these problems. We achieve state-of-the-art improvements, both in overall fidelity and equity. The source code for CounterSynth is available at https://github.com/guilherme-pombo/CounterSynth

GAMIBHEAR: whole-genome haplotype reconstruction from genome architecture mapping data

Motivation: Understanding haplotype-specific regulatory mechanisms becomes increasingly important in genomics and medical research. Investigating differences in allele-specific gene expression, epigenetic changes and their causal variants greatly benefits from haplotype reconstruction or phasing of genetic variants, but direct evidence for the haplotype structure is difficult to obtain from standard short-read sequencing data. Chromatin conformation data obtained from 3C experiments allows inference of haplotypes because inter-chromosomal contacts are more frequent than homologous intra-chromosomal contacts, but these data suffer from technical biases owing to the digestion and ligation process of the 3C technique. Genome Architecture Mapping (GAM) is a novel digestion- and ligation-free method for the inference of chromatin conformation from nuclear cryosections. Due to its high resolution and independence of enzymatic digestion it is well-suited for haplotype reconstruction and for detecting haplotype-specific chromatin contacts. Results: Here, we present GAMIBHEAR, a tool for accurate haplotype reconstruction from GAM data. GAMIBHEAR aggregates allelic co-observation frequencies across multiple nuclear slices and employs a GAM-specific probabilistic model of haplotype capture to optimise phasing accuracy. Using a hybrid mouse embryonic stem cell line with known haplotype structure as a benchmark dataset, we assess correctness and completeness of the reconstructed haplotypes, and demonstrate the power of GAM data and the accuracy of GAMIBHEAR to infer genome-wide haplotypes. Availability: GAMIBHEAR is available as an R package under the open source GPL-2 license at https://bitbucket.org/schwarzlab/gamibhear Maintainer: julia.markowski{at}mdc-berlin.d

Functional consequences of seven novel mutations in the CYP11B1 Gene: four mutations associated with nonclassic and three mutations causing classic 11 -Hydroxylase Deficiency

Context: Steroid 11β-hydroxylase (CYP11B1) deficiency (11OHD) is the second most common form of congenital adrenal hyperplasia (CAH). Cases of nonclassic 11OHD are rare compared with the incidence of nonclassic 21-hydroxylase deficiency. Objective: The aim of the study was to analyze the functional consequences of seven novel CYP11B1 mutations (p.M88I, p.W116G, p.P159L, p.A165D, p.K254_A259del, p.R366C, p.T401A) found in three patients with classic 11OHD, two patients with nonclassic 11OHD, and three heterozygous carriers for CYP11B1 mutations. Methods: We conducted functional studies employing a COS7 cell in vitro expression system comparing wild-type (WT) and mutant CYP11B1 activity. Mutants were examined in a computational three-dimensional model of the CYP11B1 protein. Results: All mutations (p.W116G, p.A165D, p.K254_A259del) found in patients with classic 11OHD have absent or very little 11β-hydroxylase activity relative to WT. The mutations detected in patients with nonclassic 11OHD showed partial functional impairment, with one patient being homozygous (p.P159L; 25% of WT) and the other patient compound heterozygous for a novel mild p.M88I (40% of WT) and the known severe p.R383Q mutation. The two mutations detected in heterozygous carriers (p.R366C, p.T401A) also reduced CYP11B1 activity by 23 to 37%, respectively. Conclusion: Functional analysis results allow for the classification of novel CYP11B1 mutations as causative for classic and nonclassic 11OHD, respectively. Four partially inactivating mutations are predicted to result in nonclassic 11OHD. These findings double the number of mild CYP11B1 mutations previously described as associated with mild 11OHD. Our data are important to predict phenotypic expression and provide important information for clinical and genetic counseling i