Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes

The compact genome of Fugu rubripes has been sequenced to over 95% coverage, and more than 80% of the assembly is in multigene-sized scaffolds. In this 365-megabase vertebrate genome, repetitive DNA accounts for less than one-sixth of the sequence, and gene loci occupy about one-third of the genome. As with the human genome, gene loci are not evenly distributed, but are clustered into sparse and dense regions. Some "giant" genes were observed that had average coding sequence sizes but were spread over genomic lengths significantly larger than those of their human orthologs. Although three-quarters of predicted human proteins have a strong match to Fugu, approximately a quarter of the human proteins had highly diverged from or had no pufferfish homologs, highlighting the extent of protein evolution in the 450 million years since teleosts and mammals diverged. Conserved linkages between Fugu and human genes indicate the preservation of chromosomal segments from the common vertebrate ancestor, but with considerable scrambling of gene order.     

AGTR2 mutations in X-linked mental retardation

Two angiotensin II (Ang II)-specific receptors, AGTR1 and AGTR2, are expressed in the mammalian brain. Ang II actions on blood pressure regulation, water electrolyte balance, and hormone secretion are primarily mediated by AGTR1. The function of AGTR2 remains unclear. Here, we show that expression of the AGTR2 gene was absent in a female patient with mental retardation (MR) who had a balanced X;7 chromosomal translocation. Additionally, 8 of 590 unrelated male patients with MR were found to have sequence changes in the AGTR2 gene, including one frameshift and three missense mutations. These findings indicate a role for AGTR2 in brain development and cognitive function.     

Noise Reversion in Paced Dogs

Pacemakers are commonly implanted by veterinary cardiologists in dogs with bradyarrhythmias. In the past, these pacemakers were placed with little attention to programming except for the basic heart rate. However, the availability of pacing programmers has permitted a better appreciation of the needs for proper and safe pacing in dogs. An awareness of the problems that can result from improper programming is imperative. We report the identification of noise reversion (inappropriate asynchronous pacing) in 42% of dogs consecutively paced (n = 19) at Cornell University during a 2 year period. Noise reversion is the operation that causes the pacemaker to switch to asynchronous pacing with repetitive refractory sensing. It was developed as a protective mechanism against noise being mistaken for cardiac events with the consequence of inhibition of pacing. However, in the dog, this operation can cause inappropriate, and potentially dangerous pacing. In the dog, this common complication is associated with the coexistence of a bradycardia and tachycardia. Proper programming of the refractory period (shortening) in conjunction with the sensitivity (decreasing the sensitivity) can eliminate noise reversion in dogs with both ventricular and atrial pacing.     

pH-sensitivity of YFP provides an intracellular indicator of programmed cell death

Background  

Programmed cell death (PCD) is an essential process for the life cycle of all multicellular organisms. In higher plants however, relatively little is known about the cascade of genes and signalling molecules responsible for the initiation and execution of PCD. To aid with the discovery and analysis of plant PCD regulators, we have designed a novel cell death assay based on low cytosolic pH as a marker of PCD.     

In vitro and in vivo susceptibility of two-drug and three-drug combinations of terbinafine, itraconazole, caspofungin, ibuprofen and fluvastatin against Pythium insidiosum

The present study investigated the in vitro inhibitory activity of terbinafine, itraconazole, caspofungin, fluvastatin and ibuprofen against 15 isolates of Pythium insidiosum in double and triple combinations and determined in vivo correlations using rabbits with experimental pythiosis. The minimal inhibitory concentration (MIC) was determined in accordance with the Clinical and Laboratory Standards Institute M 38-A2 protocol (2008), and the in vitro interactions were evaluated using a checkerboard microdilution method. For the in vivo study, 20 rabbits inoculated with P. insidiosum zoospores were divided into four groups: group 1 was treated with terbinafine and itraconazole; group 2 was treated with terbinafine, itraconazole and fluvastatin; group 3 was treated with terbinafine and caspofungin; and group 4 was the control group. Combinations of terbinafine with caspofungin or ibuprofen were synergistic for 47% of the isolates, and antagonism was not observed in any of the double combinations. The triple combinations were mostly indifferent, but synergism and antagonism were also observed. In the in vivo study, the histological aspect of the lesions was similar among the groups, but group 2 showed the lowest amount of hyphae and differed significantly from the other groups.     

The mechanobiology of mitral valve function,degeneration, and repair

In degenerative valve disease, the highly organized mitral valve leaflet matrix stratification is progressively destroyed and replaced with proteoglycan rich, mechanically inadequate tissue. This is driven by the actions of originally quiescent valve interstitial cells that become active contractile and migratory myofibroblasts. While treatment for myxomatous mitral valve disease in humans ranges from repair to total replacement, therapies in dogs focus on treating the consequences of the resulting mitral regurgitation. The fundamental gap in our understanding is how the resident valve cells respond to altered mechanical signals to drive tissue remodeling. Despite the pathological similarities and high clinical occurrence, surprisingly little mechanistic insight has been gleaned from the dog. This review presents what is known about mitral valve mechanobiology from clinical, in vivo, and in vitro data. There are a number of experimental strategies already available to pursue this significant opportunity, but success requires the collaboration between veterinary clinicians, scientists, and engineers.     

Transthoracic echocardiographically-guided interventional cardiac procedures in the dog

ObjectivesInterventional cardiac procedures are traditionally performed using fluoroscopy, or, more recently, transesophageal echocardiography (TEE). Neither modality is widely available to practicing cardiologists worldwide. We examined whether balloon valvuloplasty of pulmonic stenosis (PS) and transarterial occlusion of patent ductus arteriosus (PDA) in dogs could be performed safely with transthoracic echocardiography (TTE).AnimalsA prospective consecutive case series of 26 client-owned dogs with PS (n = 10) and PDA (n = 16).MethodsThe cardiovascular procedures were performed using TTE. Each dog was positioned on a standard echocardiography table in right lateral recumbency (dogs with PS) or left lateral recumbency (dogs with PDA). Guide wires, balloon catheters, Amplatz^® Canine Ductal Occluder (ACDO) delivery sheaths, and ACDO were imaged by standard echocardiographic views optimized to allow visualization of the defects and devices.ResultsProcedures were performed successfully without major complications in 20 dogs. In 2 dogs (German shepherds) with Type III PDA, ACDO placement was unsuccessful; 2 other German Shepherds were excluded from the procedure because their ductal diameters, measured echocardiographically, exceeded the limits of the maximal ACDO size. Two dogs weighing ≤3.5 kg had suboptimal echocardiographic visualization of the PDA and were considered too small for safe ACDO deployment. All intravascular devices at the level of the heart and great vessels appeared hyperechoic on TTE image and could be clearly monitored and guided in real-time.ConclusionsWe have demonstrated that TTE monitoring can guide each step of pulmonic balloon valvuloplasty and PDA occlusion without fluoroscopy.