Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMD(J)): electrocardiographic, echocardiographic, and morphologic studies

BACKGROUND: Cardiac mortality in Duchenne muscular dystrophy (DMD) has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. The cardiac involvement is characterized by distinctive electrocardiographic abnormalities or dilated cardiomyopathy, but the pathogenesis has remained obscure. In research on DMD, Golden retriever-based muscular dystrophy (GRMD) has attracted much attention as an animal model because it resembles DMD, but GRMD is very difficult to maintain because of their severe phenotypes. We therefore established a line of dogs with Beagle-based canine X-linked muscular dystrophy in Japan (CXMD(J)) and examined the cardiac involvement. METHODS: The cardiac phenotypes of eight CXMD(J )and four normal male dogs 2 to 21 months of age were evaluated using electrocardiography, echocardiography, and histopathological examinations. RESULTS: Increases in the heart rate and decreases in PQ interval compared to a normal littermate were detected in two littermate CXMD(J )dogs at 15 months of age or older. Distinct deep Q-waves and increase in Q/R ratios in leads II, III, and aVF were detected by 6–7 months of age in all CXMD(J )dogs. In the echocardiogram, one of eight of CXMD(J )dogs showed a hyperechoic lesion in the left ventricular posterior wall at 5 months of age, but the rest had not by 6–7 months of age. The left ventricular function in the echocardiogram indicated no abnormality in all CXMD(J )dogs by 6–7 months of age. Histopathology revealed myocardial fibrosis, especially in the left ventricular posterobasal wall, in three of eight CXMD(J )dogs by 21 months of age. CONCLUSION: Cardiac involvement in CXMD(J )dogs is milder and has slower progression than that described in GRMD dogs. The distinct deep Q-waves have been ascribed to myocardial fibrosis in the posterobasal region of the left ventricle, but our data showed that they precede the lesion on echocardiogram and histopathology. These findings imply that studies of CXMD(J )may reveal not only another causative mechanism of the deep Q-waves but also more information on the pathogenesis in the dystrophin-deficient heart

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

Dystrophin deficiency in canine X-linked muscular dystrophy in Japan (CXMDJ) alters myosin heavy chain expression profiles in the diaphragm more markedly than in the tibialis cranialis muscle

<p>Abstract</p> <p>Background</p> <p>Skeletal muscles are composed of heterogeneous collections of muscle fiber types, the arrangement of which contributes to a variety of functional capabilities in many muscle types. Furthermore, skeletal muscles can adapt individual myofibers under various circumstances, such as disease and exercise, by changing fiber types. This study was performed to examine the influence of dystrophin deficiency on fiber type composition of skeletal muscles in canine X-linked muscular dystrophy in Japan (CXMD_J), a large animal model for Duchenne muscular dystrophy.</p> <p>Methods</p> <p>We used tibialis cranialis (TC) muscles and diaphragms of normal dogs and those with CXMD_Jat various ages from 1 month to 3 years old. For classification of fiber types, muscle sections were immunostained with antibodies against fast, slow, or developmental myosin heavy chain (MHC), and the number and size of these fibers were analyzed. In addition, MHC isoforms were detected by gel electrophoresis.</p> <p>Results</p> <p>In comparison with TC muscles of CXMD_J, the number of fibers expressing slow MHC increased markedly and the number of fibers expressing fast MHC decreased with growth in the affected diaphragm. In populations of muscle fibers expressing fast and/or slow MHC(s) but not developmental MHC of CXMD_Jmuscles, slow MHC fibers were predominant in number and showed selective enlargement. Especially, in CXMD_Jdiaphragms, the proportions of slow MHC fibers were significantly larger in populations of myofibers with non-expression of developmental MHC. Analyses of MHC isoforms also indicated a marked increase of type I and decrease of type IIA isoforms in the affected diaphragm at ages over 6 months. In addition, expression of developmental (embryonic and/or neonatal) MHC decreased in the CXMD_Jdiaphragm in adults, in contrast to continuous high-level expression in affected TC muscle.</p> <p>Conclusion</p> <p>The CXMD_Jdiaphragm showed marked changes in fiber type composition unlike TC muscles, suggesting that the affected diaphragm may be effectively adapted toward dystrophic stress by switching to predominantly slow fibers. Furthermore, the MHC expression profile in the CXMD_Jdiaphragm was markedly different from that in <it>mdx </it>mice, indicating that the dystrophic dog is a more appropriate model than a murine one, to investigate the mechanisms of respiratory failure in DMD.</p

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

Left gaze bias in humans, rhesus monkeys and domestic dogs

While viewing faces, human adults often demonstrate a natural gaze bias towards the left visual field, that is, the right side of the viewee’s face is often inspected first and for longer periods. Using a preferential looking paradigm, we demonstrate that this bias is neither uniquely human nor limited to primates, and provide evidence to help elucidate its biological function within a broader social cognitive framework. We observed that 6-month-old infants showed a wider tendency for left gaze preference towards objects and faces of different species and orientation, while in adults the bias appears only towards upright human faces. Rhesus monkeys showed a left gaze bias towards upright human and monkey faces, but not towards inverted faces. Domestic dogs, however, only demonstrated a left gaze bias towards human faces, but not towards monkey or dog faces, nor to inanimate object images. Our findings suggest that face- and species-sensitive gaze asymmetry is more widespread in the animal kingdom than previously recognised, is not constrained by attentional or scanning bias, and could be shaped by experience to develop adaptive behavioural significance

Evaluation of the effects of a VEGFR-2 inhibitor compound on alanine aminotransferase gene expression and enzymatic activity in the rat liver

Article deposited according to agreement with BMC, December 6, 2010.YesFunding provided by the Open Access Authors Fund

Persisting right-sided chylothorax in a patient with chronic lymphocytic leukemia: a case report

Introduction Chylothorax caused by chronic lymphocytic leukemia is very rare and the best therapeutic approach, especially the role of modern immunochemotherapy, is not yet defined. Case presentation We present the case of a 65-year-old male Caucasian patient with right-sided chylothorax caused by a concomitantly diagnosed chronic lymphocytic leukemia. As first-line treatment four cycles of an immunochemotherapy, consisting of fludarabine, cyclophosphamide and rituximab were administered. In addition, our patient received total parenteral nutrition for the first two weeks of treatment. Despite the very good clinical response of the lymphoma to treatment, the chylothorax persisted and percutaneous radiotherapy of the thoracic duct was applied. However, eight weeks after the radiotherapy the chylothorax still persisted and our patient agreed to a surgical intervention. A ligation of the thoracic duct via a muscle sparing thoracotomy was performed, resulting in a complete cessation of the pleural effusion. Apart from the first two weeks our patient was treated on an out-patient basis for nearly six months. Conclusion In this case of chylothorax caused by chronic lymphocytic leukemia, immunochemotherapy in combination with conservative treatment, and even consecutive radiotherapy, were not able to stop pleural effusion, despite the very good clinical response of the chronic lymphocytic leukemia to treatment. Out-patient management using repetitive thoracocenteses can be safe as bridging until definitive surgical ligation of the thoracic duct

Longitudinal ambulatory measurements of gait abnormality in dystrophin-deficient dogs

Chantier qualité GAInternational audienceABSTRACT: BACKGROUND: This study aimed to measure the gait abnormalities in GRMD (Golden retriever muscular dystrophy) dogs during growth and disease progression using an ambulatory gait analyzer (3D-accelerometers) as a possible tool to assess the effects of a therapeutic intervention. METHODS: Six healthy and twelve GRMD dogs were evaluated twice monthly, from the age of two to nine months. The evolution of each gait variable previously shown to be modified in control and dystrophin-deficient adults was assessed using two-ways variance analysis (age, clinical status) with repeated measurements. A principal component analysis (PCA) was applied to perfect multivariate data interpretation. RESULTS: Speed, stride length, total power and force significantly already decreased (p < 0.01) at the age of 2 months. The other gait variables (stride frequency, relative power distributions along the three axes) became modified at later stages. Using the PCA analysis, a global gait index taking into account the main gait variables was calculated, and was also consistent to detect the early changes in the GRMD gait patterns, as well as the progressive degradation of gait quality. CONCLUSION: The gait variables measured by the accelerometers were sensitive to early detect and follow the gait disorders and mirrored the heterogeneity of clinical presentations, giving sense to monitor gait in GRMD dogs during progression of the disease and pre-clinical therapeutic trials

Burning in Banksia Woodlands: How Does the Fire-Free Period Influence Reptile Communities?

Fire is an important management tool for both hazard reduction burning and maintenance of biodiversity. The impact of time since last fire on fauna is an important factor to understand as land managers often aim for prescribed burning regimes with specific fire-free intervals. However, our current understanding of the impact of time since last fire on fauna is largely unknown and likely dependent on vegetation type. We examined the responses of reptiles to fire age in banksia woodlands, and the interspersed melaleuca damplands among them, north of Perth, Western Australia, where the current prescribed burning regime is targeting a fire-free period of 8–12 years. The response of reptiles to fire was dependent on vegetation type. Reptiles were generally more abundant (e.g. Lerista elegans and Ctenophorus adelaidensis) and specious in banksia sites. Several species (e.g. Menetia greyii, Cryptoblepharus buchananii) preferred long unburnt melaleuca sites (>16 years since last fire, YSLF) compared to recently burnt sites (<12 YSLF). Several of the small elapids (e.g. the WA priority listed species Neelaps calonotus) were only detected in older-aged banksia sites (>16 YSLF). The terrestrial dragon C. adelaidensis and the skink Morethia obscura displayed a strong response to fire in banksia woodlands only. Highest abundances of the dragon were detected in the recently burnt (<7 YSLF) and long unburnt (>35 YSLF) banksia woodlands, while the skink was more abundant in older sites. Habitats from a range of fire ages are required to support the reptiles we detected, especially the longer unburnt (>16 YSLF) melaleuca habitat. Current burning prescriptions are reducing the availability of these older habitats

Possible explosion crater origin of small lake basins with raised rims on Titan

The Cassini mission discovered lakes and seas comprising mostly methane in the polar regions of Titan. Lakes of liquid nitrogen may have existed during the epochs of Titan’s past in which methane was photochemically depleted, leaving a nearly pure molecular nitrogen atmosphere and, thus, far colder temperatures. The modern-day small lake basins with sharp edges have been suggested to originate from dissolution processes, due to their morphological similarity to terrestrial karstic lakes. Here we analyse the morphology of the small lake basins that feature raised rims to elucidate their origin, using delay-Doppler processed altimetric and bathymetric data acquired during the last close flyby of Titan by the Cassini spacecraft. We find that the morphology of the raised-rim basins is analogous to that of explosion craters from magma–water interaction on Earth and therefore propose that these basins are from near-surface vapour explosions, rather than karstic. We calculate that the phase transition of liquid nitrogen in the near subsurface during a warming event can generate explosions sufficient to form the basins. Hence, we suggest that raised-rim basins are evidence for one or more warming events terminating a nitrogen-dominated cold episode on Titan