Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway.

BackgroundDevelopment of neural and vascular systems displays astonishing similarities among vertebrates. This parallelism is under a precise control of complex guidance signals and neurovascular interactions. Previously, our group identified a highly conserved neural protein called thrombospondin type I domain containing 7A (THSD7A). Soluble THSD7A promoted and guided endothelial cell migration, tube formation and sprouting. In addition, we showed that thsd7a could be detected in the nervous system and was required for intersegmental vessels (ISV) patterning during zebrafish development. However, the exact origin of THSD7A and its effect on neurovascular interaction remains unclear.ResultsIn this study, we discovered that zebrafish thsd7a was expressed in the primary motor neurons. Knockdown of Thsd7a disrupted normal primary motor neuron formation and ISV sprouting in the Tg(kdr:EGFP/mnx1:TagRFP) double transgenic zebrafish. Interestingly, we found that Thsd7a morphants displayed distinct phenotypes that are very similar to the loss of Notch-delta like 4 (dll4) signaling. Transcript profiling further revealed that expression levels of notch1b and its downstream targets, vegfr2/3 and nrarpb, were down-regulated in the Thsd7a morphants. These data supported that zebrafish Thsd7a could regulate angiogenic sprouting via Notch-dll4 signaling during development.ConclusionsOur results suggested that motor neuron-derived Thsd7a plays a significant role in neurovascular interactions. Thsd7a could regulate ISV angiogenesis via Notch-dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development of both neural and vascular systems

Prospectives

Tiré de: Prospectives, vol. 22, no 1, février 1986.Titre de l'écran-titre (visionné le 24 janv. 2013

Refractive errors in children with autism in a developing country

Background: In a resource.limited country visual problems of mentally challenged individuals are often neglected.Aim: The present study aims to study refractive errors in children diagnosed with autism in a developing country.Materials and Methods: Ophthalmic examination was carried out on children diagnosed with autism attending a school for the mentally  challenged in Enugu, Nigeria between December 2009 and May 2010. Visual acuity was assessed using Lea symbols. Anterior and posterior segments were examined. Cycloplegic refraction was performed. Datawas entered on the protocol prepared for the study and analyzed using Statistical Package for the Social Sciences version 17 (Chicago IL, USA).Results: A total of 21 children with autism were enrolled in the school; 18 of whom were examined giving coverage of 85.7%. The age range was 5.15 years, with a mean of 10.28 years (standard deviation } 3.20). There were 13 boys and 5 girls. One child had bilateral temporal pallor of the disc and one had bilateral maculopathy with diffuse chorioretinal atrophy.  Refraction revealed 4 children (22.2%) had astigmatism and 2 children (11.1%) had hypermetropia.Conclusion: Significant refractive error mainly astigmatism was noted in the children with autism. Identifying refractive errors in these children early and providing appropriate corrective lenses may help optimize their visual functioning and impact their activities of daily life in a positive way.Key words: Autism, developing country, refractive erro

Hydrogen peroxide detection with quartz-enhanced photoacoustic spectroscopy using a distributed-feedback quantum cascade laser

A quartz-enhanced photoacoustic spectroscopy sensor system was developed for the sensitive detection of hydrogen peroxide (H2O2) using its absorption transitions in the v6 fundamental band at ∼7.73 μm. The recent availability of distributed-feedback quantum cascade lasers provides convenient access to a strong H2O2 absorption line located at 1295.55 cm−1. Sensor calibration was performed by means of a water bubbler that generated titrated average H2O2vapor concentrations. A minimum detection limit of 12 parts per billion (ppb) corresponding to a normalized noise equivalent absorption coefficient of 4.6 × 10−9 cm−1W/Hz1/2 was achieved with an averaging time of 100 s

The effect of sepsis and its inflammatory response on mechanical clot characteristics: a prospective observational study

Purpose: Sepsis and its progression are known to have a major influence on the coagulation system. Current coagulation tests are of limited use when assessing coagulation in sepsis patients. This study aims to assess the potential for a new functional biomarker of clot microstructure, fractal dimension, to identify changes in the mechanical properties of clot microstructure across the sepsis spectrum (sepsis, severe sepsis and septic shock). Methods: A total of 100 patients that presented acutely to a large teaching hospital were included in this prospective observational study (50 sepsis, 20 severe sepsis and 30 septic shock) against a matched control of 44 healthy volunteers. Fractal analysis was performed, as well as standard markers of coagulation, and six plasma markers of inflammation. Results: Fractal dimension was significantly higher in the sepsis and severe sepsis groups than the healthy control (1.78 ± 0.07 and 1.80 ± 0.05 respectively vs 1.74 ± 0.03) (p < 0.001), indicating a significant increase in mechanical clot strength and elasticity consistent with a hypercoagulable state. Conversely, fractal dimension was significantly lower in septic shock (1.66 ± 0.10, p < 0.001), indicating a significant reduction in mechanical clot strength and functionality consistent with a hypocoagulable state. This corresponded with a significant increase in the inflammatory response. Conclusions: This study confirms that clot microstructure is significantly altered through the various stages of sepsis. Of particular importance was the marked change in clot development between severe sepsis and septic shock, which has not been previously reported

Centrally concentrated molecular gas driving galactic-scale ionized gas outflows in star-forming galaxies

We perform a joint analysis of high spatial resolution molecular gas and star-formation rate (SFR) maps in main-sequence star-forming galaxies experiencing galactic-scale outflows of ionized gas. Our aim is to understand the mechanism that determines which galaxies are able to launch these intense winds. We observed CO(1→0) at 1-arcsec resolution with ALMA in 16 edge-on galaxies, which also have 2-arcsec spatial-resolution optical integral field observations from the SAMI Galaxy Survey. Half the galaxies in the sample were previously identified as harbouring intense and large-scale outflows of ionized gas (‘outflow types’) and the rest serve as control galaxies. The data set is complemented by integrated CO(1→0) observations from the IRAM 30-m telescope to probe the total molecular gas reservoirs. We find that the galaxies powering outflows do not possess significantly different global gas fractions or star-formation efficiencies when compared with a control sample. However, the ALMA maps reveal that the molecular gas in the outflow-type galaxies is distributed more centrally than in the control galaxies. For our outflow-type objects, molecular gas and star-formation are largely confined within their inner effective radius (reff), whereas in the control sample, the distribution is more diffuse, extending far beyond reff. We infer that outflows in normal star-forming galaxies may be caused by dynamical mechanisms that drive molecular gas into their central regions, which can result in locally enhanced gas surface density and star-formation

Population Pharmacokinetics of Telapristone (CDB-4124) and its Active Monodemethylated Metabolite CDB-4453, with a Mixture Model for Total Clearance

Telapristone is a selective progesterone antagonist that is being developed for the long-term treatment of symptoms associated with endometriosis and uterine fibroids. The population pharmacokinetics of telapristone (CDB-4124) and CDB-4453 was investigated using nonlinear mixed-effects modeling. Data from two clinical studies (n = 32) were included in the analysis. A two-compartment (parent) one compartment (metabolite) mixture model (with two populations for apparent clearance) with first-order absorption and elimination adequately described the pharmacokinetics of telapristone and CDB-4453. Telapristone was rapidly absorbed with an absorption rate constant (Ka) of 1.26 h−1. Moderate renal impairment resulted in a 74% decrease in Ka. The population estimates for oral clearance (CL/F) for the two populations were 11.6 and 3.34 L/h, respectively, with 25% of the subjects being allocated to the high-clearance group. Apparent volume of distribution for the central compartment (V2/F) was 37.4 L, apparent inter-compartmental clearance (Q/F) was 21.9 L/h, and apparent peripheral volume of distribution for the parent (V4/F) was 120 L. The ratio of the fraction of telapristone converted to CDB-4453 to the distribution volume of CDB-4453 (Fmetest) was 0.20/L. Apparent volume of distribution of the metabolite compartment (V3/F) was fixed to 1 L and apparent clearance of the metabolite (CLM/F) was 2.43 L/h. A two-compartment parent-metabolite model adequately described the pharmacokinetics of telapristone and CDB-4453. The clearance of telapristone was separated into two populations and could be the result of metabolism via polymorphic CYP3A5

Joint modelling of confounding factors and prominent genetic regulators provides increased accuracy in genetical genomics studies.

Expression quantitative trait loci (eQTL) studies are an integral tool to investigate the genetic component of gene expression variation. A major challenge in the analysis of such studies are hidden confounding factors, such as unobserved covariates or unknown subtle environmental perturbations. These factors can induce a pronounced artifactual correlation structure in the expression profiles, which may create spurious false associations or mask real genetic association signals. Here, we report PANAMA (Probabilistic ANAlysis of genoMic dAta), a novel probabilistic model to account for confounding factors within an eQTL analysis. In contrast to previous methods, PANAMA learns hidden factors jointly with the effect of prominent genetic regulators. As a result, this new model can more accurately distinguish true genetic association signals from confounding variation. We applied our model and compared it to existing methods on different datasets and biological systems. PANAMA consistently performs better than alternative methods, and finds in particular substantially more trans regulators. Importantly, our approach not only identifies a greater number of associations, but also yields hits that are biologically more plausible and can be better reproduced between independent studies. A software implementation of PANAMA is freely available online at http://ml.sheffield.ac.uk/qtl/

Microstructural Evolution in Thin Films of Electronic Materials

Contains reports on ten research projects.Joint Services Electronics Program Contract DAAL03-89-C-0001National Science FoundationU.S. Air Force - Office of Scientific Research Contract AFOSR 85-0154Semiconductor Research CorporationAT&TInternational Business Machines CorporationNational Institutes of Healt