Stroke-associated pattern of gene expression previously identified by machine-learning is diagnostically robust in an independent patient population

Our group recently employed genome-wide transcriptional profiling in tandem with machine-learning based analysis to identify a ten-gene pattern of differential expression in peripheral blood which may have utility for detection of stroke. The objective of this study was to assess the diagnostic capacity and temporal stability of this stroke-associated transcriptional signature in an independent patient population. Publicly available whole blood microarray data generated from 23 ischemic stroke patients at 3, 5, and 24 h post-symptom onset, as well from 23 cardiovascular disease controls, were obtained via the National Center for Biotechnology Information Gene Expression Omnibus. Expression levels of the ten candidate genes (ANTXR2, STK3, PDK4, CD163, MAL, GRAP, ID3, CTSZ, KIF1B, and PLXDC2) were extracted, compared between groups, and evaluated for their discriminatory ability at each time point. We observed a largely identical pattern of differential expression between stroke patients and controls across the ten candidate genes as reported in our prior work. Furthermore, the coordinate expression levels of the ten candidate genes were able to discriminate between stroke patients and controls with levels of sensitivity and specificity upwards of 90% across all three time points. These findings confirm the diagnostic robustness of the previously identified pattern of differential expression in an independent patient population, and further suggest that it is temporally stable over the first 24 h of stroke pathology

Vegetative propagation of dieback-tolerant Fraxinus excelsior on

book chapterThis publication is based on the work of Action FP1103 FRAXBACK, supported by COST (European Cooperation in Science and Technology)Ash trees which are tolerant to Hymenoscyphus fraxineus may be selected in all age classes among heavily infected populations. They may be produced also by controlled crossings of disease tolerant trees, because the genetic component of inheritance for disease tolerance is high. For mature and juvenile plant material, the deployment of disease tolerant genotypes could be potentially achieved by vegetatively propagating selected genotypes. We describe a system to vegetatively propagate selected ash genotypes and we discuss the prospects and options for using vegetative propagation on all age classes of trees. Mature trees were rejuvenated through the process of micropropagation to establish mother plants in large trays which were cut back repeatedly (hedged) to produce at least two crops of cuttings per year. The rooting capacity of ten genotypes was tested by a commercial nursery over a period of three years, to assess the feasibility of using hedged mother plants for efficient propagation. Commercial practise was to treat cuttings with 0.25% IBA, insert them in plug pots and maintain them covered with fine plastic within low plastic tunnels in a non heated greenhouse and without supplementary heating at the cutting base. In the first year, the mean rooting rate was 53 % for the first crop of cuttings and 35 % for the second. In the second and third years the rooting rates improved to over 80% for each crop of cuttings as experience was gained in handling the material. Rooting rate varied among the genotypes. We assessed the growth and development of micropropagated ash trees in the field from an observation clonal trial, consisting of four mature genotypes which had been established in 2002 in five replicate plots. The micropropagated trees were generally similar in height and dbh to seed derived control trees and developed normally. These observations are discussed in the context of using vegetative propagation as a tool in breeding and for the large scale deployment of ash with tolerance to H. fraxineus.European Cooperation in Science and Technolog

Hubble Space Telescope survey of the Perseus Cluster -III: The effect of local environment on dwarf galaxies

We present the results of a Hubble Space Telescope (HST) study of dwarf galaxies in the outer regions of the nearby rich Perseus Cluster, down to M_V = -12, and compare these with the dwarf population in the cluster core from our previous HST imaging. In this paper we examine how properties such as the colour magnitude relation, structure and morphology are affected by environment for the lowest mass galaxies. Dwarf galaxies are excellent tracers of the effects of environment due to their low masses, allowing us to derive their environmentally based evolution, which is more subtle in more massive galaxies. We identify 11 dwarf elliptical (dE) and dwarf spheroidal (dSph) galaxies in the outer regions of Perseus, all of which are previously unstudied. We measure the (V-I)_0 colours of our newly discovered dEs, and find that these dwarfs lie on the same red sequence as those in the cluster core. The morphologies of these dwarfs are examined by quantifying their light distributions using CAS parameters, and we find that dEs in the cluster outskirts are on average more disturbed than those in the core, with =0.13\pm0.09 and =0.18\pm0.08, compared to =0.02\pm0.04, =0.01\pm0.07 for those in the core. Based on these results, we infer that these objects are ``transition dwarfs'', likely in the process of transforming from late-type to early type galaxies as they infall into the cluster, with their colours transforming before their structures. When we compare the number counts for both the core and outer regions of the cluster, we find that below M_V = -12, the counts in the outer regions of the cluster exceed those in the core. This is evidence that in the very dense region of the cluster, dwarfs are unable to survive unless they are sufficiently massive to prevent their disruption by the cluster potential and interactions with other galaxies.Comment: 14 pages, 11 figures. MNRAS accepte

The surface-associated exopolysaccharide of Bifidobacterium longum 35624 plays an essential role in dampening host proinflammatory responses and repressing local TH17 responses

The immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immune-regulatory activity are not well defined. It has previously been demonstrated that B. longum 35624 produces a cell surface exopolysaccharide (sEPS), and in this study, we investigated the role played by this exopolysaccharide in influencing the host immune response. B. longum 35624 induced relatively low levels of cytokine secretion from human dendritic cells, whereas an isogenic exopolysaccharide-negative mutant derivative (termed sEPSneg) induced vastly more cytokines, including interleukin-17 (IL-17), and this response was reversed when exopolysaccharide production was restored in sEPSneg by genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPSneg did not protect against the development of colitis, with associated enhanced recruitment of IL-17+ lymphocytes to the gut. Moreover, intranasal administration of sEPSneg also resulted in enhanced recruitment of IL-17+ lymphocytes to the murine lung. These data demonstrate that the particular exopolysaccharide produced by B. longum 35624 plays an essential role in dampening proinflammatory host responses to the strain and that loss of exopolysaccharide production results in the induction of local TH17 responses. IMPORTANCE: Particular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensal-host interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro. In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surface-associated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Multicohort analysis of the maternal age effect on recombination

Several studies have reported that the number of crossovers increases with maternal age in humans, but others have found the opposite. Resolving the true effect has implications for understanding the maternal age effect on aneuploidies. Here, we revisit this question in the largest sample to date using single nucleotide polymorphism (SNP)-chip data, comprising over 6,000 meioses from nine cohorts. We develop and fit a hierarchical model to allow for differences between cohorts and between mothers. We estimate that over 10 years, the expected number of maternal crossovers increases by 2.1% (95% credible interval (0.98%, 3.3%)). Our results are not consistent with the larger positive and negative effects previously reported in smaller cohorts. We see heterogeneity between cohorts that is likely due to chance effects in smaller samples, or possibly to confounders, emphasizing that care should be taken when interpreting results from any specific cohort about the effect of maternal age on recombination

Formation of superdense hadronic matter in high energy heavy-ion collisions

We present the detail of a newly developed relativistic transport model (ART 1.0) for high energy heavy-ion collisions. Using this model, we first study the general collision dynamics between heavy ions at the AGS energies. We then show that in central collisions there exists a large volume of sufficiently long-lived superdense hadronic matter whose local baryon and energy densities exceed the critical densities for the hadronic matter to quark-gluon plasma transition. The size and lifetime of this matter are found to depend strongly on the equation of state. We also investigate the degree and time scale of thermalization as well as the radial flow during the expansion of the superdense hadronic matter. The flow velocity profile and the temperature of the hadronic matter at freeze-out are extracted. The transverse momentum and rapidity distributions of protons, pions and kaons calculated with and without the mean field are compared with each other and also with the preliminary data from the E866/E802 collaboration to search for experimental observables that are sensitive to the equation of state. It is found that these inclusive, single particle observables depend weakly on the equation of state. The difference between results obtained with and without the nuclear mean field is only about 20\%. The baryon transverse collective flow in the reaction plane is also analyzed. It is shown that both the flow parameter and the strength of the ``bounce-off'' effect are very sensitive to the equation of state. In particular, a soft equation of state with a compressibility of 200 MeV results in an increase of the flow parameter by a factor of 2.5 compared to the cascade case without the mean field. This large effect makes it possible to distinguish the predictions from different theoretical models and to detect the signaturesComment: 55 pages, latex, + 39 figures available upon reques

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Getting aligned on representational alignment

Biological and artificial information processing systems form representations that they can use to categorize, reason, plan, navigate, and make decisions. How can we measure the extent to which the representations formed by these diverse systems agree? Do similarities in representations then translate into similar behavior? How can a system's representations be modified to better match those of another system? These questions pertaining to the study of representational alignment are at the heart of some of the most active research areas in cognitive science, neuroscience, and machine learning. For example, cognitive scientists measure the representational alignment of multiple individuals to identify shared cognitive priors, neuroscientists align fMRI responses from multiple individuals into a shared representational space for group-level analyses, and ML researchers distill knowledge from teacher models into student models by increasing their alignment. Unfortunately, there is limited knowledge transfer between research communities interested in representational alignment, so progress in one field often ends up being rediscovered independently in another. Thus, greater cross-field communication would be advantageous. To improve communication between these fields, we propose a unifying framework that can serve as a common language between researchers studying representational alignment. We survey the literature from all three fields and demonstrate how prior work fits into this framework. Finally, we lay out open problems in representational alignment where progress can benefit all three of these fields. We hope that our work can catalyze cross-disciplinary collaboration and accelerate progress for all communities studying and developing information processing systems. We note that this is a working paper and encourage readers to reach out with their suggestions for future revisions.Comment: Working paper, changes to be made in upcoming revision

Development of Genomic Resources for Pacific Herring through Targeted Transcriptome Pyrosequencing

Pacific herring (Clupea pallasii) support commercially and culturally important fisheries but have experienced significant additional pressure from a variety of anthropogenic and environmental sources. In order to provide genomic resources to facilitate organismal and population level research, high-throughput pyrosequencing (Roche 454) was carried out on transcriptome libraries from liver and testes samples taken in Prince William Sound, the Bering Sea, and the Gulf of Alaska. Over 40,000 contigs were identified with an average length of 728 bp. We describe an annotated transcriptome as well as a workflow for single nucleotide polymorphism (SNP) discovery and validation. A subset of 96 candidate SNPs chosen from 10,933 potential SNPs, were tested using a combination of Sanger sequencing and high-resolution melt-curve analysis. Five SNPs supported between-ocean-basin differentiation, while one SNP associated with immune function provided high differentiation between Prince William Sound and Kodiak Island within the Gulf of Alaska. These genomic resources provide a basis for environmental physiology studies and opportunities for marker development and subsequent population structure analysis