Searching for "monogenic diabetes" in dogs using a candidate gene approach

BACKGROUND: Canine diabetes is a common endocrine disorder with an estimated breed-related prevalence ranging from 0.005% to 1.5% in pet dogs. Increased prevalence in some breeds suggests that diabetes in dogs is influenced by genetic factors and similarities between canine and human diabetes phenotypes suggest that the same genes might be associated with disease susceptibility in both species. Between 1-5% of human diabetes cases result from mutations in a single gene, including maturity onset diabetes of the adult (MODY) and neonatal diabetes mellitus (NDM). It is not clear whether monogenic forms of diabetes exist within some dog breeds. Identification of forms of canine monogenic diabetes could help to resolve the heterogeneity of the condition and lead to development of breed-specific genetic tests for diabetes susceptibility. RESULTS: Seventeen dog breeds were screened for single nucleotide polymorphisms (SNPs) in eighteen genes that have been associated with human MODY/NDM. Six SNP associations were found from five genes, with one gene (ZFP57) being associated in two different breeds. CONCLUSIONS: Some of the genes that have been associated with susceptibility to MODY and NDM in humans appear to also be associated with canine diabetes, although the limited number of associations identified in this study indicates canine diabetes is a heterogeneous condition and is most likely to be a polygenic trait in most dog breeds. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2052-6687-1-8) contains supplementary material, which is available to authorized users

Altered cortical activation patterns associated with baroreflex unloading following 24 h of physical deconditioning

Cardiovascular arousal is associated with patterned cortical activity changes. Head-down-tilt bed rest (HDBR) dimishes the baroreflex-mediated cardiac control. The present study tested the hypothesis that HDBR deconditioning would modify the forebrain organization for heart rate (HR) control during baroreflex unloading. Heart rate variability (HRV), blood pressure and plasma hormones were analysed at rest, whereas HR and cortical autonomic activation patterns (functional magnetic resonance imaging) were measured during graded and randomly assigned lower body negative pressure treatments (LBNP, -15 and -35 mmHg) both before (Pre) and after (Post) a 24 h HDBR protocol (study 1; n= 8). An additional group was tested before and following diuretic-induced hypovolaemia (study 2; n= 9; spironolactone, 100 mg day-1 for 3 days) that mimicked the plasma volume lost during HDBR (-15% in both studies; P \u3c 0.05). Head-down bed rest with hypovolaemia did not affect baseline HR, mean arterial pressure, HRV or plasma catecholamines. Head-down bed rest augmented the LBNP-induced HR response (P \u3c 0.05), and this was associated with bed-rest-induced development of the following changes: (i) enhanced activation within the genual anterior cingulate cortex and the right anterior insular cortex; and (ii) deactivation patterns within the subgenual regions of the anterior cingulate cortex. Diuretic treatment (without HDBR) did not affect baseline HR and mean arterial pressure, but did reduce resting HRV and elevated circulating noradrenaline and plasma renin activity (P \u3c 0.05). The greater HR response to LBNP following diuretic (P \u3c 0.05) was associated with diminished activation of the right anterior insula. Our findings indicate that 24 h of HDBR minimized the impact of diuretic treatment on baseline autonomic and cardiovascular variables. The findings also indicate that despite the similar augmentation of HR responses to LBNP and despite similar pre-intervention cortical activation patterns, HDBR and diuretic treatment produced different effects on the cortical responses, with HDBR affecting anterior cingulate cortex and right insula regions, whereas diuretic treatment affected primarily the right insula alone, but in a direction that was opposite to HDBR. The data indicate that physical deconditioning can induce rapid functional changes within the cortical circuitry associated with baroreflex unloading, changes that are distinct from diuretic-induced hypovolaemia. The results suggest that physical activity patterns exert a rapid and notable impact on the cortical circuitry associated with cardiovascular control. © 2012 The Physiological Society

The VLA Galactic Plane Survey

The VLA Galactic Plane Survey (VGPS) is a survey of HI and 21-cm continuum emission in the Galactic plane between longitude 18 degrees 67 degr. with latitude coverage from |b| < 1.3 degr. to |b| < 2.3 degr. The survey area was observed with the Very Large Array (VLA) in 990 pointings. Short-spacing information for the HI line emission was obtained by additional observations with the Green Bank Telescope (GBT). HI spectral line images are presented with a resolution of 1 arcmin x 1 arcmin x 1.56 km/s (FWHM) and rms noise of 2 K per 0.824 km/s channel. Continuum images made from channels without HI line emission have 1 arcmin (FWHM) resolution. VGPS images are compared with images from the Canadian Galactic Plane Survey (CGPS) and the Southern Galactic Plane Survey (SGPS). In general, the agreement between these surveys is impressive, considering the differences in instrumentation and image processing techniques used for each survey. The differences between VGPS and CGPS images are small, < 6 K (rms) in channels where the mean HI brightness temperature in the field exceeds 80 K. A similar degree of consistency is found between the VGPS and SGPS. The agreement we find between arcminute resolution surveys of the Galactic plane is a crucial step towards combining these surveys into a single uniform dataset which covers 90% of the Galactic disk: the International Galactic Plane Survey (IGPS). The VGPS data will be made available on the World Wide Web through the Canadian Astronomy Data Centre (CADC).Comment: Accepted for publication in The Astronomical Journal. 41 pages, 13 figures. For information on data release, colour images etc. see http://www.ras.ucalgary.ca/VGP

The Phenomenon of Exquisite Motor Control in Tic Disorders and its Pathophysiological Implications

The unifying characteristic of movement disorders is the phenotypic presentation of abnormal motor outputs, either as isolated phenomena or in association with further clinical, often neuropsychiatric, features. However, the possibility of a movement disorder also characterized by supranormal or enhanced volitional motor control has not received attention. Based on clinical observations and cases collected over a number of years, we here describe the intriguing clinical phenomenon that people with tic disorders are often able to control specific muscle contractions as part of their tic behaviors to a degree that most humans typically cannot. Examples are given in accompanying video documentation. We explore medical literature on this topic and draw analogies with early research of fine motor control physiology in healthy humans. By systematically analyzing the probable sources of this unusual capacity, and focusing on neuroscientific accounts of voluntary motor control, sensory feedback, and the role of motor learning in tic disorders, we provide a novel pathophysiological account explaining both the presence of exquisite control over motor output and that of overall tic behaviors. We finally comment on key questions for future research on the topic and provide concluding remarks on the complex movement disorder of tic behaviors

Nondestructive Electromagnetic Material Characterization using a Dual Waveguide Probe: A Full Wave Solution

A nondestructive technique for determining the complex permittivity and permeability of a perfect electric conductor backed magnetic shielding material using a dual waveguide probe is presented. The dual waveguide probe allows for the simultaneous collection of reflection and transmission coefficients which distinguishes it from single probe methods common in the literature. Theoretical development of these coefficients, which is accomplished through a coupled magnetic field integral equations formulation using Love\u27s equivalence principle and solved via the method of moments (MOM), is discussed. Evaluation of the resulting MOM impedance matrix elements is performed using complex plane integration leading to enhanced computational efficiency and physical insight. Comparison of the theoretical and measured reflection and transmission coefficients using a root finding algorithm leads to the desired permittivity and permeability. Measurement results of a magnetic shielding material are presented and compared to traditional methods for the purpose of validating the new technique. The probe\u27s sensitivity to aperture alignment, sample thickness, and flange thickness is also investigated.Abstract © AGU

GSH23.0-0.7+117, a neutral hydrogen shell in the inner Galaxy

GSH23.0-0.7+117 is a well-defined neutral hydrogen shell discovered in the VLA Galactic Plane Survey (VGPS). Only the blueshifted side of the shell was detected. The expansion velocity and systemic velocity were determined through the systematic behavior of the HI emission with velocity. The center of the shell is at (l,b,v)=(23.05,-0.77,+117 km/s). The angular radius of the shell is 6.8', or 15 pc at a distance of 7.8 kpc. The HI mass divided by the volume of the half-shell implies an average density n_H = 11 +/- 4 cm^{-3} for the medium in which the shell expanded. The estimated age of GSH23.0-0.7+117 is 1 Myr, with an upper limit of 2 Myr. The modest expansion energy of 2 * 10^{48} erg can be provided by the stellar wind of a single O4 to O8 star over the age of the shell. The 3 sigma upper limit to the 1.4 GHz continuum flux density (S_{1.4} < 248 mJy) is used to derive an upper limit to the Lyman continuum luminosity generated inside the shell. This upper limit implies a maximum of one O9 star (O8 to O9.5 taking into account the error in the distance) inside the HI shell, unless most of the incident ionizing flux leaks through the HI shell. To allow this, the shell should be fragmented on scales smaller than the beam (2.3 pc). If the stellar wind bubble is not adiabatic, or the bubble has burst (as suggested by the HI channel maps), agreement between the energy and ionization requirements is even less likely. The limit set by the non-detection in the continuum provides a significant challenge for the interpretation of GSH23.0-0.7+117 as a stellar wind bubble. A similar analysis may be applicable to other Galactic HI shells that have not been detected in the continuum.Comment: 18 pages, 6 figures. Figures 1 and 4 separately in GIF format. Accepted for publication in Astrophysical Journa