Heterozygote effects in mice with partial truncations in the growth hormone receptor cytoplasmic domain: Assessment of growth parameters and phenotype

The GH receptor (GHR) is essential for normal postnatal growth and development, and the molecular basis of GHR action has been studied intensively. Clinical case studies and more recently mouse models have revealed the extensive phenotype of impaired GH action. We recently reported two new mouse models, possessing cytoplasmic truncations at position 569 (plus Y539/545-F) and 391, which were created to identify functional subdomains within the cytoplasmic signaling domain. In the homozygous state, these animals show progressively impaired postnatal growth coupled with complex changes in gene expression. We describe here an extended phenotype analysis encompassing the heterozygote state to identify whether single copies of these mutant receptors bring about partial or dominant-negative phenotypes. It appears that the retention of the ubiquitin-dependent endocytosis motif the N-terminal cytoplasmic domain permits turnover of these mutant receptors because no dominant-negative phenotype is seen. Nonetheless, we do observe partial impairment of postnatal growth in heterozygotes supporting limited haploinsufficiency. Reproductive function is impaired in these models in a progressive manner, in parallel with loss of signal transducer and activator of transcription-5 activation ability. In summary, we describe a more comprehensive phenotypic analysis of these mouse models, encompassing overall and longitudinal body growth, reproductive function, and hormonal status in both the heterozygote and homozygote state. Our results suggest that patients expressing single copies of similarly mutated GHRs would not display an obvious clinical phenotype.

Neogenin interacts with RGMa and Netrin-1 to guide axons within the embryonic vertebrate forebrain

In the embryonic forebrain, pioneer axons establish a simple topography of dorsoventral and longitudinal tracts. The cues used by these axons during the initial formation of the axon scaffold remain largely unknown. We have investigated the axon guidance role of Neogenin, a member of the immunoglobulin (Ig) superfamily that binds to the chemoattractive ligand Netrin-1, as well as to the chemorepulsive ligand repulsive guidance molecule (RGMa). Here, we show strong expression of Neogenin and both of its putative ligands in the developing Xenopus forebrain. Neogenin loss-of-function mutants revealed that this receptor was essential for axon guidance in an early forming dorsoventral brain pathway. Similar mutant phenotypes were also observed following loss of either RGMa or Netrin-1. Simultaneous partial knock downs of these molecules revealed dosage-sensitive interactions and confirmed that these receptors and ligands were acting in the same pathway. The results provide the first evidence that Neogenin acts as an axon guidance molecule in vivo and support a model whereby Neogenin-expressing axons respond to a combination of attractive and repulsive cues as they navigate their ventral trajectory. (c) 2006 Elsevier Inc. All rights reserved.

Evaluation of resynchronization of contractile function following biventricular pacing using colour tissue Doppler imaging

Biventdcular (BV) pacing is evaluated as an alternative treatment for patients with dilated cardiomyppathy (both ischemic and non-ischemic) and end-stage heart failure. Colour tissue Doppler imaging using echocardiography allows noninvasive, quantitative assessment of radial motion in the long-axis with measurement of peak systolic velocity timing. The aim of the present study was to evaluate quantitatively, the systolic performance of the left ventricle and the resynchrenization of contraction (before vs after implantation). Patients and methods: 25 patients with dilated cardiomyopathy (11 ischemic), NYHA class III or IV, QRS duration >120 ms received a biventricular pacemaker. Routine 2D echo and colour tissue Doppler imaging were performed before and within 1 week following implantation. LVEF was assessed using the biplane Sampson's method.Peak systolic velocity (PSV) and time to PSV (TPV) were assessed in 4 regions (basal anterior, inferior, lateral and septal). By averaging the TPV from all 4 regions, a synchronization index was dedved from these measurements. Reaults: LVEF improved by 9±9% following pacing; 17 patients improved LVEF 5% or more. The change in PSV in the septal and lateral regions related significantly to the change in LVEF (r=0.74, r=0.62).The change in synchronization index before vs after pacing (as a measurement of REsynchronization) was related to the change in LVEF (y=120x+5.6, r=0.79, P

Determinants of visual 2-D echo assessment of left ventricular wall motion: Comparison with myocardial thickening on cardiac magnetic resonance imaging

Background: left ventricular wall motion on 2d echo (2de) is usually scored visually. we sought to examine the determinants of visually assessed wall motion scoring on 2de by comparison with myocardial thickening quantified on MRI. Methods: using a 16 segment model, we studied 287 segments in 30 patients aged 61+/ -11 years (6 female), with ischaemic LV dysfunction (defined by at least 2 segments dysfunctional on 2de). 2de was performed in 5 views and wall motion scores (WMS) assigned: 1 (normal) 103 segments, 2 (hypokinetic) 93 segments, 3 (akinetic) 87 segments. MRI was used to measure end systolic wall thickness (ESWT), end diastolic wall thickness (EDWT) and percentage systolic wall thickening (SWT%) in the plane of the 2de and to assess WMS in the same planes visually. No patient had a clinical ischemic event between the tests. Results: visual assessment of wall motion by 2de and MRI showed moderate agreement (kappa = 0.425). Resting 2de wall motion correlated significantly (p

Motion vector encryption in multimedia streaming

Streaming video application requires high security as well as high computational performance. In video encryption, traditional selective algorithms have been used to partially encrypt the relatively important data in order to satisfy the streaming performance requirement. Most video selective encryption algorithms are inherited from still image encryption algorithms, the encryption on motion vector data is not considered. The assumption is that motion vector data are not as important as pixel image data. Unfortunately, in some cases, motion vector itself may be sufficient enough to leak out useful video information. Normally motion vector data consume over half of the whole video stream bandwidth, neglecting their security may be unwise. In this paper, we target this security problem and illustrate attacks at two different levels that can restore useful video information using motion vectors only. Further, an information analysis is made and a motion vector information model is built. Based on this model, we describe a new motion vector encryption algorithm called MVEA. We show the experimental results of MVEA. The security strength and performance of the algorithm are also evaluated.

Helicopter automation using a low-cost sensing system

This paper details the design of an autonomous helicopter control system using a low cost sensor suite. Control is maintained using simple nested PID loops. Aircraft attitude, velocity, and height is estimated using an in-house designed IMU and vision system. Information is combined using complimentary filtering. The aircraft is shown to be stabilised and responding to high level demands on all axes, including heading, height, lateral velocity and longitudinal velocity.