Testing the boundaries of closely related daisy taxa using metabolomic profiling

Advances in high-throughput, comprehensive small molecule analytical techniques have seen the development of the field of metabolomics. The coupling of mass spectrometry with high-resolution chromatography provides extensive chemical profiles from complex biological extracts. These profiles include thousands of compounds linked to gene expression, and can be used as taxonomic characters. Studies have shown metabolite profiles to be taxon specific in a range of organisms, but few have investigated taxonomically problematic plant taxa. This study used a phenetic analysis of metabolite profiles to test taxonomic boundaries in the Olearia phlogopappa (Asteraceae) complex as delimited by morphological data. Metabolite profiles were generated from both field- and shade house-grown material, using liquid chromatography-mass spectrometry (LC-MS). Aligned profiles of 51 samples from 12 taxa gave a final dataset of over 10,000 features. Multivariate analyses of field and shade house material gave congruent results, both confirming the distinctiveness of the morphologically defined species and subspecies in this complex. Metabolomics has great potential in alpha taxonomy, especially for testing the boundaries of closely related taxa where DNA sequence data has been uninformative

SEARCHING FOR DEBRIS DISKS AROUND SEVEN RADIO PULSARS

We report on our searches for debris disks around seven relatively nearby radio pulsars, which are isolated sources that were carefully selected as targets on the basis of our deep Ks-band imaging survey. The Ks images obtained with the 6.5m Baade Magellan Telescope at Las Campanas Observatory are analyzed together with the Spitzer/IRAC images at 4.5 and 8.0μm and the WISE images at 3.4, 4.6, 12, and 22μm. No infrared counterparts of these pulsars are found, with flux upper limits of ∼μJy at near-infrared (λ < 10μm) and ∼10–1000μJy at mid-infrared wavelengths (λ > 10 μm). The results of this search are discussed in terms of the efficiency of converting the pulsar spin-down energy to thermal energy and X-ray heating of debris disks, with a comparison made of the two magnetars 4U 0142+61 and 1E 2259+586, which are suggested to harbor a debris disk.published_or_final_versio

Hepatitis C virus exploits cyclophilin A to evade PKR

Counteracting innate immunity is essential for successful viral replication. Host cyclophilins (Cyps) have been implicated in viral evasion of host antiviral responses, although the mechanisms are still unclear. Here, we show that hepatitis C virus (HCV) co-opts the host protein CypA to aid evasion of antiviral responses dependent on the effector protein kinase R (PKR). Pharmacological inhibition of CypA rescues PKR from antagonism by HCV NS5A, leading to activation of an interferon regulatory factor-1 (IRF1)-driven cell intrinsic antiviral program that inhibits viral replication. These findings further the understanding of the complexity of Cyp-virus interactions, provide mechanistic insight into the remarkably broad antiviral spectrum of Cyp inhibitors, and uncover novel aspects of PKR activity and regulation. Collectively, our study identifies a novel antiviral mechanism that harnesses cellular antiviral immunity to suppress viral replication

Left Ventricular Outflow Tract Obstruction Defined by Active Three-Dimensional Echocardiography Using Rotational Transthoracic Acquisition

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75675/1/j.1540-8175.1994.tb01105.x.pd

Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells

This is the final version of the article. Available from eLife Sciences Publications via the DOI in this record.Type 1 diabetes (T1D) is an autoimmune disease caused by loss of pancreatic β cells via apoptosis while neighboring α cells are preserved. Viral infections by coxsackieviruses (CVB) may contribute to trigger autoimmunity in T1D. Cellular permissiveness to viral infection is modulated by innate antiviral responses, which vary among different cell types. We presently describe that global gene expression is similar in cytokine-treated and virus-infected human islet cells, with up-regulation of gene networks involved in cell autonomous immune responses. Comparison between the responses of rat pancreatic α and β cells to infection by CVB5 and 4 indicate that α cells trigger a more efficient antiviral response than β cells, including higher basal and induced expression of STAT1-regulated genes, and are thus better able to clear viral infections than β cells. These differences may explain why pancreatic β cells, but not α cells, are targeted by an autoimmune response during T1D.Fonds De La Recherche Scientifique – FNRS: FNRS- F 5/4/5.MCF/KP. Project de secherche (PDR) T.0036.13; European Commission (EC): Projects Naimit and BetaBat, in the Framework Programme 7 of the European Community; Federation Wallonie- Bruxelles: the Communaute Franc¸ aise de BelgiqueActions de Recherche Concertees (ARC); Fonds De La Recherche Scientifique – FNRS: FNRS post-doctoral fellowship; Governo Brasil: PDE/CSF Pos-Doutorado no Exterior; Juvenile Diabetes Research Foundation International (JDRF): JDRF Career Development Award; European Commission (EC): European Union’s Seventh Framework Programme [FP7/2007-2013] under grant agreement 261441 PEVNE

Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children

Functional central limit theorems for vicious walkers

We consider the diffusion scaling limit of the vicious walker model that is a system of nonintersecting random walks. We prove a functional central limit theorem for the model and derive two types of nonintersecting Brownian motions, in which the nonintersecting condition is imposed in a finite time interval $(0,T]$ for the first type and in an infinite time interval $(0,\infty)$ for the second type, respectively. The limit process of the first type is a temporally inhomogeneous diffusion, and that of the second type is a temporally homogeneous diffusion that is identified with a Dyson's model of Brownian motions studied in the random matrix theory. We show that these two types of processes are related to each other by a multi-dimensional generalization of Imhof's relation, whose original form relates the Brownian meander and the three-dimensional Bessel process. We also study the vicious walkers with wall restriction and prove a functional central limit theorem in the diffusion scaling limit.Comment: AMS-LaTeX, 20 pages, 2 figures, v6: minor corrections made for publicatio

Assessing connectivity between an overlying aquifer and a coal seam gas resource using methane isotopes, dissolved organic carbon and tritium

Coal seam gas (CSG) production can have an impact on groundwater quality and quantity in adjacent or overlying aquifers. To assess this impact we need to determine the background groundwater chemistry and to map geological pathways of hydraulic connectivity between aquifers. In south-east Queensland (Qld), Australia, a globally important CSG exploration and production province, we mapped hydraulic connectivity between the Walloon Coal Measures (WCM, the target formation for gas production) and the overlying Condamine River Alluvial Aquifer (CRAA), using groundwater methane (CH4) concentration and isotopic composition (δ13C-CH4), groundwater tritium (3H) and dissolved organic carbon (DOC) concentration. A continuous mobile CH4 survey adjacent to CSG developments was used to determine the source signature of CH4 derived from the WCM. Trends in groundwater δ13C-CH4 versus CH4 concentration, in association with DOC concentration and 3H analysis, identify locations where CH4 in the groundwater of the CRAA most likely originates from the WCM. The methodology is widely applicable in unconventional gas development regions worldwide for providing an early indicator of geological pathways of hydraulic connectivity

Quantitative evaluation of recall and precision of CAT Crawler, a search engine specialized on retrieval of Critically Appraised Topics

BACKGROUND: Critically Appraised Topics (CATs) are a useful tool that helps physicians to make clinical decisions as the healthcare moves towards the practice of Evidence-Based Medicine (EBM). The fast growing World Wide Web has provided a place for physicians to share their appraised topics online, but an increasing amount of time is needed to find a particular topic within such a rich repository. METHODS: A web-based application, namely the CAT Crawler, was developed by Singapore's Bioinformatics Institute to allow physicians to adequately access available appraised topics on the Internet. A meta-search engine, as the core component of the application, finds relevant topics following keyword input. The primary objective of the work presented here is to evaluate the quantity and quality of search results obtained from the meta-search engine of the CAT Crawler by comparing them with those obtained from two individual CAT search engines. From the CAT libraries at these two sites, all possible keywords were extracted using a keyword extractor. Of those common to both libraries, ten were randomly chosen for evaluation. All ten were submitted to the two search engines individually, and through the meta-search engine of the CAT Crawler. Search results were evaluated for relevance both by medical amateurs and professionals, and the respective recall and precision were calculated. RESULTS: While achieving an identical recall, the meta-search engine showed a precision of 77.26% (±14.45) compared to the individual search engines' 52.65% (±12.0) (p < 0.001). CONCLUSION: The results demonstrate the validity of the CAT Crawler meta-search engine approach. The improved precision due to inherent filters underlines the practical usefulness of this tool for clinicians