Long-term palliation of right-sided congestive heart failure after stenting a recurrent cor triatriatum dexter in a 10½-year-old pug.

A 10½-year-old, male neutered, pug presented with increasing ascites over two months. Echocardiography revealed cor triatriatum dexter with no concurrent cardiovascular anomalies, subsequently confirmed by computed tomography angiography. Balloon dilation of the perforated intra-atrial membrane under fluoroscopic guidance resulted in the transient resolution of all clinical abnormalities, but six months later stenosis and ascites recurred. After repeated balloon dilation, a stent was placed across the membrane. The dog remains asymptomatic fourteen months after the second procedure. One noteworthy feature of this case is the onset of congestive heart failure due to a congenital defect only at more than 10 years of age

Modified Rate-Theory Predictions in Comparison to Microstructural Data

Standard rate theory methods have recently been combined with experimental microstructures to successfully reproduce measured swelling behavior in ternary steels around 400 C. Fit parameters have reasonable values except possibly for the recombination radius, R{sub c}, which can be larger than expected. Numerical simulations of void nucleation and growth reveal the importance additional recombination processes at unstable clusters. Such extra recombination may reduce the range of possible values for R{sub c}. A modified rate theory is presented here that includes the effect of these undetectably small defect clusters. The fit values for R{sub c} are not appreciably altered, as the modification has little effect on the model behavior in the late steady state. It slightly improves the predictions for early transient times, when the sink strength of stable voids and dislocations is relatively small. Standard rate theory successfully explains steady swelling behavior in high purity stainless steel

Isochronal annealing effects on local structure, crystalline fraction, and undamaged region size of radiation damage in Ga-stabilized δ\delta-Pu

The effects on the local structure due to self-irradiation damage of Ga stabilized $\delta$-Pu stored at cryogenic temperatures have been examined using extended x-ray absorption fine structure (EXAFS) experiments. Extensive damage, seen as a loss of local order, was evident after 72 days of storage below 15 K. The effect was observed from both the Pu and Ga sites, although less pronounced around Ga. Isochronal annealing was performed on this sample to study the annealing processes that occur between cryogenic and room temperature storage conditions, where damage is mostly reversed. Damage fractions at various points along the annealing curve have been determined using an amplitude-ratio method, standard EXAFS fitting, and a spherical crystallite model, and provide information complementary to previous electrical resistivity- and susceptibility-based isochronal annealing studies. The use of a spherical crystallite model accounts for the changes in EXAFS spectra using just two parameters, namely, the crystalline fraction and the particle radius. Together, these results are discussed in terms of changes to the local structure around Ga and Pu throughout the annealing process and highlight the unusual role of Ga in the behavior of the lowest temperature anneals.Comment: 13 pages, 10 figure

Notch signaling during human T cell development

Notch signaling is critical during multiple stages of T cell development in both mouse and human. Evidence has emerged in recent years that this pathway might regulate T-lineage differentiation differently between both species. Here, we review our current understanding of how Notch signaling is activated and used during human T cell development. First, we set the stage by describing the developmental steps that make up human T cell development before describing the expression profiles of Notch receptors, ligands, and target genes during this process. To delineate stage-specific roles for Notch signaling during human T cell development, we subsequently try to interpret the functional Notch studies that have been performed in light of these expression profiles and compare this to its suggested role in the mouse

Disturbed Processing of Contextual Information in HCN3 Channel Deficient Mice

Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) in the nervous system are implicated in a variety of neuronal functions including learning and memory, regulation of vigilance states and pain. Dysfunctions or genetic loss of these channels have been shown to cause human diseases such as epilepsy, depression, schizophrenia, and Parkinson's disease. The physiological functions of HCN1 and HCN2 channels in the nervous system have been analyzed using genetic knockout mouse models. By contrast, there are no such genetic studies for HCN3 channels so far. Here, we use a HCN3-deficient (HCN3(-/-)) mouse line, which has been previously generated in our group to examine the expression and function of this channel in the CNS. Specifically, we investigate the role of HCN3 channels for the regulation of circadian rhythmand for the determination of behavior. Contrary to previous suggestions we find that HCN3(-/-) mice show normal visual, photic, and non-photic circadian function. In addition, HCN3(-/-) mice are impaired in processing contextual information, which is characterized by attenuated long-term extinction of contextual fear and increased fear to a neutral context upon repeated exposure

PhenoWorld : a new paradigm to screen rodent behavior

Modeling depression in animals has inherent complexities that are augmented by intrinsic difficulties to measure the characteristic features of the disorder. Herein, we describe the PhenoWorld (PhW), a new setting in which groups of six rats lived in an ethological enriched environment, and have their feeding, locomotor activity, sleeping and social behavior automatically monitored. A battery of emotional and cognitive tests was used to characterize the behavioral phenotype of animals living in the PhW and in standard conditions (in groups of six and two rats), after exposure to an unpredictable chronic mild stress paradigm (uCMS) and antidepressants. Data reveal that animals living in the PhW displayed similar, but more striking, behavioral differences when exposed to uCMS, such as increased behavioral despair shown in the forced swimming test, resting/sleep behavior disturbances and reduced social interactions. Moreover, several PhW-cage behaviors, such as spontaneous will to go for food or exercise in running wheels, proved to be sensitive indicators of depressive-like behavior. In summary, this new ethological enriched paradigm adds significant discriminative power to screen depressive-like behavior, in particularly rodent's hedonic behavior

Core module biomarker identification with network exploration for breast cancer metastasis

<p>Abstract</p> <p>Background</p> <p>In a complex disease, the expression of many genes can be significantly altered, leading to the appearance of a differentially expressed "disease module". Some of these genes directly correspond to the disease phenotype, (i.e. "driver" genes), while others represent closely-related first-degree neighbours in gene interaction space. The remaining genes consist of further removed "passenger" genes, which are often not directly related to the original cause of the disease. For prognostic and diagnostic purposes, it is crucial to be able to separate the group of "driver" genes and their first-degree neighbours, (i.e. "core module") from the general "disease module".</p> <p>Results</p> <p>We have developed COMBINER: COre Module Biomarker Identification with Network ExploRation. COMBINER is a novel pathway-based approach for selecting highly reproducible discriminative biomarkers. We applied COMBINER to three benchmark breast cancer datasets for identifying prognostic biomarkers. COMBINER-derived biomarkers exhibited 10-fold higher reproducibility than other methods, with up to 30-fold greater enrichment for known cancer-related genes, and 4-fold enrichment for known breast cancer susceptible genes. More than 50% and 40% of the resulting biomarkers were cancer and breast cancer specific, respectively. The identified modules were overlaid onto a map of intracellular pathways that comprehensively highlighted the hallmarks of cancer. Furthermore, we constructed a global regulatory network intertwining several functional clusters and uncovered 13 confident "driver" genes of breast cancer metastasis.</p> <p>Conclusions</p> <p>COMBINER can efficiently and robustly identify disease core module genes and construct their associated regulatory network. In the same way, it is potentially applicable in the characterization of any disease that can be probed with microarrays.</p

Effects of NK-4 in a Transgenic Mouse Model of Alzheimer's Disease

Beta-amyloid (Aβ) peptides are considered to play a major role in the pathogenesis of Alzheimer's disease (AD) and molecules that can prevent pathways of Aβ toxicity may be potential therapeutic agents for treatment of AD. We have previously reported that NK-4, a cyanine photosensitizing dye, displays neurotrophic and antioxidant activities. In this study, we report the effects of NK-4 on the toxicity of Aβ and on cognitive function and Aβ concentration in a transgenic mouse model of AD (Tg2576). In vitro, NK-4 effectively protected neuronal cells from toxicity induced by Aβ. In addition, it displayed profound inhibitory activities on Aβ fibril formation. In vivo, Tg2576 mice received an intraperitoneal injection at 100 or 500 µg/kg of NK-4 once a day, five times a week for 9 months. Administration of NK-4 to the mice attenuated impairment of recognition memory, associative memory, and learning ability, as assessed by a novel object recognition test, a passive avoidance test, and a water maze test, respectively. NK-4 decreased the brain Aβ concentration while increasing the plasma amyloid level in a dose-dependent manner. NK-4 also improved memory impairments of ICR mice induced by direct intracerebroventricular administration of Aβ. These lines of evidence suggest that NK-4 may affect multiple pathways of amyloid pathogenesis and could be useful for treatment of AD