High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene.

Chromosome 17q11-q21 is a region of the genome likely to harbor susceptibility to autism (MIM(209850)) based on earlier evidence of linkage to the disorder. This linkage is specific to multiplex pedigrees containing only male probands (MO) within the Autism Genetic Resource Exchange (AGRE). Earlier, Stone et al.(1) completed a high-density single nucleotide polymorphism association study of 13.7 Mb within this interval, but common variant association was not sufficient to account for the linkage signal. Here, we extend this single nucleotide polymorphism-based association study to complete the coverage of the two-LOD support interval around the chromosome 17q linkage peak by testing the majority of common alleles in 284 MO trios. Markers within an interval containing the gene, CACNA1G, were found to be associated with Autism Spectrum Disorder at a locally significant level (P=1.9 × 10(-5)). While establishing CACNA1G as a novel candidate gene for autism, these alleles do not contribute a sufficient genetic effect to explain the observed linkage, indicating that there is substantial genetic heterogeneity despite the clear linkage signal. The region thus likely harbors a combination of multiple common and rare alleles contributing to the genetic risk. These data, along with earlier studies of chromosomes 5 and 7q3, suggest few if any major common risk alleles account for Autism Spectrum Disorder risk under major linkage peaks in the AGRE sample. This provides important evidence for strategies to identify Autism Spectrum Disorder genes, suggesting that they should focus on identifying rare variants and common variants of small effect

Ex vivo magnetic sentinel lymph node detection in colorectal cancer with a SPIO tracer

A new method for selecting sentinel lymph nodes (SNs) in colorectal cancer tissue was investigated in 12 patients. A tracer consisting of superparamagnetic ironoxide (SPIO) nanoparticles was injected in the resected tissue. A handheld magnetic probe was used to select SNs to which the SPIO was drained. Vibrating sample magnetometry was performed on the lymph nodes to quantify the amount of SPIO in the nodes. High-field MRI allowed to depict the distribution of SPIO in the node, and revealed small anatomical structures. One or more SPIO containing nodes were successfully selected with the magnetic probe in all 12 patients

Ligand-targeted liposomes directed against pathological vasculature

The development of liposomes targeted to angiogenic endothelial cells offers exciting prospects for intervention in cancer and inflammation. Several proteins are (strongly) over-expressed on angiogenic endothelial cells as compared to the quiescent endothelium, and could potentially serve as targets for site-specific drug delivery. In this contribution particular attention is given to the design of targeted long-circulating liposomes directed against the alpha v beta 3-integrin protein

Effect of pH of amine fluoride containing toothpastes on enamel remineralization in vitro

<p>Abstract</p> <p>Background</p> <p>One of the important factors of the demineralization and remineralization equilibrium of enamel is the pH of the surrounding solutions. Effort has been laid in the formulation of different fluoride compounds and the fluoride content in toothpastes but much less is known about the influence of the pH of the toothpastes on their effectiveness. It was therefore the aim of this study to investigate the influence of different pH levels on enamel remineralization in an in vitro experiment using polarization light microscopy and EDX quantitative element analysis.</p> <p>Methods</p> <p>A 5 × 5 mm window on the enamel surface of 40 caries free extracted human premolars was demineralized in a hydroxyethylcellulose solution at pH 4.8. The teeth were divided into 8 groups and the lower half of the window was covered with varnish serving as control. Each group was then immersed in toothpaste slurry containing amine fluoride (1400 ppm) at pH 4.1, 4.5, 5.1 and 6.9 or control toothpaste slurry without fluoride at pH 4.3, 4.7, 5.3 and 7.0. Serial sections were cut through the lesions and investigated with polarization light microscopy and quantitative EDX element analysis.</p> <p>Results</p> <p>The PLM results showed a decreased porous volume of the body of the lesion after incubation with fluoridated toothpaste at pH 4.53 and 5.16. No differences between the experimental window and the control window were found in the other groups. The quantitative element analysis showed no differences in the element content of any of the groups.</p> <p>Conclusion</p> <p>From the results it can be concluded that slightly acidified fluoridated dentifrices may have a certain positive effect on enamel remineralization.</p

Effect of fluoride toothpastes on enamel demineralization

BACKGROUND: It was the aim of this study to investigate the effect of four different toothpastes with differing fluoride compounds on enamel remineralization. METHODS: A 3 × 3 mm window on the enamel surface of 90 human premolars was demineralized in a hydroxyethylcellulose solution at pH 4.8. The teeth were divided into 6 groups and the lower half of the window was covered with varnish serving as control. The teeth were immersed in a toothpaste slurry containing: placebo tooth paste (group 1); remineralization solution (group 2); Elmex Anticaries (group 3); Elmex Sensitive (group 4); Blend-a-med Complete (group 5) and Colgate GRF (group 6). Ten teeth of each group were used for the determination of the F(- )content in the superficial enamel layer and acid solubility of enamel expressed in soluble phosphorus. Of 6 teeth of each group serial sections were cut and investigated with polarization light microscopy (PLM) and quantitative energy dispersive X-ray analysis (EDX). RESULTS: The PLM results showed an increased remineralization of the lesion body in the Elmex Anticaries, Elmex Sensitive and Colgate GRF group but not in the Blend-a-med group. A statistically significant higher Ca content was found in the Elmex Anticaries group. The fluoride content in the superficial enamel layer was significantly increased in both Elmex groups and the Blend-a-med group. Phosphorus solubility was significantly decreased in both Elmex groups and the Blend-a-med group. CONCLUSION: It can be concluded that amine fluoride compounds in toothpastes result in a clearly marked remineralization of caries like enamel lesions followed by sodium fluoride and sodium monofluorophosphate formulations

Orbital Elements and Stellar Parameters of the Active Binary UX Arietis

This is the final version of the article. Available from American Astronomical Society via the DOI in this record.Stellar activity observed as large surface spots, radio flares, or emission lines is often found in binary systems. UX Arietis exhibits these signs of activity, originating on the K0 subgiant primary component. Our aim is to resolve the binary, measure the orbital motion, and provide accurate stellar parameters such as masses and luminosities to aid in the interpretation of the observed phenomena. Using the CHARA six-telescope optical long-baseline array on Mount Wilson, California, we obtained amplitudes and phases of the interferometric visibility on baselines up to 330 m in length, resolving the two components of the binary. We reanalyzed archival Center for Astrophysics spectra to disentangle the binary component spectra and the spectrum of the third component, which was resolved by speckle interferometry. We also obtained new spectra with the Nordic Optical Telescope, and we present new photometric data that we use to model stellar surface spot locations. Both interferometric visibilities and spectroscopic radial velocities are modeled with a spotted primary stellar surface using the Wilson–Devinney code. We fit the orbital elements to the apparent orbit and radial velocity data to derive the distance (52.1 ± 0.8 pc) and stellar masses (MP = 1.30 0.06 M, MS = 1.14 0.06 M). The radius of the primary can be determined to be RP = 5.6 0.1 R and that of the secondary to be RS = 1.6 0.2 R. The equivalent spot coverage of the primary component was found to be 62% with an effective temperature 20% below that of the unspotted surface.We thank Robert Wilson (University of Florida) for providing a custom version of his code to compute images of spotted stellar surfaces and for his help with using it. This work is based upon observations obtained with the Georgia State University (GSU) Center for High Angular Resolution Astronomy (CHARA) array at Mount Wilson Observatory. The CHARA array is supported by the National Science Foundation under grant numbers AST-1211929 and AST-1411654. Institutional support has been provided by the GSU College of Arts and Sciences and the GSU Office of the Vice President for Research and Economic Development. The MIRC instrument at the CHARA array was funded by the University of Michigan. F.B., R.R., and J.D.M. acknowledge support from NSF-AST 1210972 and 1108963. G.T. acknowledges partial support from NSF grant AST-1509375. S.K. acknowledges support from an STFC Rutherford Fellowship (ST/J004030/1) and ERC Starting Grant (grant agreement no. 639889). This work is also based on observations made with the Nordic Optical Telescope (NOT), operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. This research has made use of the SIMBAD database, operated at the CDS, Strasbourg, France. This research has made use of the Jean-Marie Mariotti Center SearchCal service13 codeveloped by FIZEAU and LAOG/IPAG and of the CDS astronomical databases SIMBAD and VIZIER.14 This research has made use of the Washington Double Star Catalog, maintained at the U.S. Naval Observatory. We thank Nicholas Elias II for discussions. We thank Dimitri Pourbaix for maintaining and providing access to the SB9 database of RV measurements of spectroscopic binaries

The Expanding Fireball of Nova Delphini 2013

A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages could result from interactions with the companion during the common envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting from one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 +/- 0.59 kpc from the Sun.Comment: Published in Nature. 32 pages. Final version available at http://www.nature.com/nature/journal/v515/n7526/full/nature13834.htm

Effect of Global Cardiac Ischemia on Human Ventricular Fibrillation: Insights from a Multi-scale Mechanistic Model of the Human Heart

Acute regional ischemia in the heart can lead to cardiac arrhythmias such as ventricular fibrillation (VF), which in turn compromise cardiac output and result in secondary global cardiac ischemia. The secondary ischemia may influence the underlying arrhythmia mechanism. A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global ischemia the dominant frequency of activation decreased, while after reperfusion it increased rapidly. At the same time the complexity of epicardial excitation, measured as the number of epicardical phase singularity points, remained approximately constant during ischemia. Here we perform numerical studies based on these clinical data and propose explanations for the observed dynamics of the period and complexity of activation patterns. In particular, we study the effects on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an anatomically accurate model of human heart ventricles. We demonstrate that the fall of dominant frequency in VF during secondary ischemia can be explained by an increase in extracellular potassium, while the increase during reperfusion is consistent with washout of potassium and continued activation of the ATP-dependent potassium channels. We also suggest that memory effects are responsible for the observed complexity dynamics. In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements

Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming

BACKGROUND: Although chronic morbidity in humans from soil transmitted helminth (STH) infections can be reduced by anthelmintic treatment, inconsistent diagnostic tools make it difficult to reliably measure the impact of deworming programs and often miss light helminth infections. METHODS: Cryopreserved stool samples from 796 people (aged 2-81 years) in four villages in Bungoma County, western Kenya, were assessed using multi-parallel qPCR for 8 parasites and compared to point-of-contact assessments of the same stools by the 2-stool 2-slide Kato-Katz (KK) method. All subjects were treated with albendazole and all Ascaris lumbricoides expelled post-treatment were collected. Three months later, samples from 633 of these people were re-assessed by both qPCR and KK, re-treated with albendazole and the expelled worms collected. RESULTS: Baseline prevalence by qPCR (n = 796) was 17 % for A. lumbricoides, 18 % for Necator americanus, 41 % for Giardia lamblia and 15% for Entamoeba histolytica. The prevalence was <1% for Trichuris trichiura, Ancylostoma duodenale, Strongyloides stercoralis and Cryptosporidium parvum. The sensitivity of qPCR was 98% for A. lumbricoides and N. americanus, whereas KK sensitivity was 70% and 32%, respectively. Furthermore, qPCR detected infections with T. trichiura and S. stercoralis that were missed by KK, and infections with G. lamblia and E. histolytica that cannot be detected by KK. Infection intensities measured by qPCR and by KK were correlated for A. lumbricoides (r = 0.83, p < 0.0001) and N. americanus (r = 0.55, p < 0.0001). The number of A. lumbricoides worms expelled was correlated (p < 0.0001) with both the KK (r = 0.63) and qPCR intensity measurements (r = 0.60). CONCLUSIONS: KK may be an inadequate tool for stool-based surveillance in areas where hookworm or Strongyloides are common or where intensity of helminth infection is low after repeated rounds of chemotherapy. Because deworming programs need to distinguish between populations where parasitic infection is controlled and those where further treatment is required, multi-parallel qPCR (or similar high throughput molecular diagnostics) may provide new and important diagnostic information