Molecular characterisation of virulence graded field isolates of myxoma virus

<p>Abstract</p> <p>Background</p> <p><it>Myxoma virus </it>(MV) has been endemic in Europe since shortly after its deliberate release in France in 1952. While the emergence of more resistant hosts and more transmissible and attenuated virus is well documented, there have been relatively few studies focused on the sequence changes incurred by the virus as it has adapted to its new host. In order to identify regions of variability within the MV genome to be used for phylogenetic studies and to try to investigate causes of MV strain attenuation we have molecularly characterised nine strains of MV isolated in Spain between the years 1992 and 1995 from wide ranging geographic locations and which had been previously graded for virulence by experimental infection of rabbits.</p> <p>Results</p> <p>The findings reported here show the analysis of 16 genomic regions accounting for approximately 10% of the viral genomes. Of the 20 genes analysed 5 (M034L, M069L, M071L, M130R and M135R) were identical in all strains and 1 (M122R) contained only a single point mutation in an individual strain. Four genes (M002L/R, M009L, M036L and M017L) showed insertions or deletions that led to disruption of the ORFs.</p> <p>Conclusions</p> <p>The findings presented here provide valuable tools for strain differentiation and phylogenetic studies of MV isolates and some clues as to the reasons for virus attenuation in the field.</p

Uric acid metabolism in pre-hypertension and the metabolic syndrome

In humans uric acid (UA) is the end product of degradation of purines. The handling of UA by the renal system is a complex process which is not fully understood. To date, several urate transporters in the renal proximal tubule have been identified. Among them, urate transporter 1 (URAT1) and a glucose transporter 9 (GLUT9) are considered of greater importance, as potential targets for treatment of hyperuricemia and the potential associated cardio-metabolic risk. Therefore, the recognition of the metabolic pathway of UA and elucidation of occurrence of hyperuricemia may provide important insights about the relationship between UA, pre-hypertension (preHT) and the metabolic syndrome (MetS). We also review the available clinical studies in this field, including experimental studies dealing with the mechanisms of UA transport via different transporters, as well as current treatment options for hyperuricemia in patients with MetS, preHT or cardiovascular risk factors. © 2014 Bentham Science Publishers

Host-specificity of myxoma virus: Pathogenesis of South American and North American strains of myxoma virus in two North American lagomorph species

The pathogenesis of South American and North American myxoma viruses was examined in two species of North American lagomorphs, Sylvilagus nuttallii (mountain cottontail) and Sylvilagus audubonii (desert cottontail) both of which have been shown to have the potential to transmit the South American type of myxoma virus. Following infection with the South American strain (Lausanne, Lu), S. nuttallii developed both a local lesion and secondary lesions on the skin. They did not develop the classical myxomatosis seen in European rabbits (Oryctolagus cuniculus). The infection at the inoculation site did not resolve during the 20-day time course of the trial and contained transmissible virus titres at all times. In contrast, S. audubonii infected with Lu had very few signs of disseminated infection and partially controlled virus replication at the inoculation site. The prototype Californian strain of myxoma virus (MSW) was able to replicate at the inoculation site of both species but did not induce clinical signs of a disseminated infection. In S. audubonii, there was a rapid response to MSW characterised by a massive T lymphocyte infiltration of the inoculation site by day 5. MSW did not reach transmissible titres at the inoculation site in either species. This might explain why the Californian myxoma virus has not expanded its host-range in North America. Crow

Endurance training protects the heart during maximal exercise in long-distance runners

Introduction Cardiac function (cardiac output) and oxygen extraction (arterio-venous O2 difference) are key physiological determinants of maximal oxygen consumption and endurance performance. Purpose The aim of the study was to determine differences in maximal cardiac function represented by cardiac output and cardiac power output and oxygen extraction represented by arterio-venous O2 difference between long-distance runners and age- and gender-matched healthy individuals. Methods In a prospective observational study, 63 healthy males were recruited: 47 long-distance (half- and full-marathon) runners (aged 32.6 ± 8.6 years, body mass index 23.4 ± 2.2 kg/m²) and 16 healthy untrained individuals (control group, aged 30.9 ± 11.2 years, body mass index 24.8 ± 2.4 kg/m²). All participants underwent maximal graded cardiopulmonary exercise stress seting using an electromagnetic cycle ergometer with simultanous monitoring of metabolic (gas exchange) and hemodynamic (bioreactance) measurements. Cardiac power output, expressed in watts, as a measure of overall function and pumping capability of the heart, was determined as the product between cardiac output and mean arterial blood pressure. Oxygen extraction (arterio-venous O2 difference) was calculated as the ratio between O2 consumption and cardiac output. Results Maximal O2 consumption was significantly lower in the control group compared to runners (absolute values, 3.44 ± 1.12 vs. 3.99 ± 0.52 L/min, p &amp;lt; 0.01; and relative values, 45.3 ± 16.4 vs. 53.6 ± 6.9 ml/kg/min, p &amp;lt; 0.01). However, maximal cardiac output and cardiac power output were significantly higher in the control group compared to runners (21.4 ± 3.9 vs. 18.7 ± 3.0 L/min, p = 0.02; 5.94 ± 1.35 vs. 5.01 ± 1.00 watts, p = 0.01). Maximal stroke volume was significantly higher in control group compared to runners (126 ± 28 vs. 109 ± 21 ml/beat, p = 0.04), whereas maximal heart rate was not significantly different betwen the groups (174 ± 12 vs. 177 ± 22 beats/min, p = 0.70). Arterio-venous O2 difference was significantly higher in runners compared to control group (21.6 ± 3.7 vs. 14.5 ± 3.6 mlO2/100 ml blood, p &amp;lt; 0.01). Conclusion During maximal exercise stress testing long-distance runners demonstrate higher cardiorespiratory fitness and oxygen extraction but lower cardiac output and cardiac power output compared to untrained indivuduals. Ability to extract and utilise more oxygen at lower cardiac output during maximal physiogical stress suggests cardiac protective role of endurance training in long-distance runners

Host-specificity of myxoma virus: Pathogenesis of South American and North American strains of myxoma virus in two North American lagomorph species

The pathogenesis of South American and North American myxoma viruses was examined in two species of North American lagomorphs, Sylvilagus nuttallii (mountain cottontail) and Sylvilagus audubonii (desert cottontail) both of which have been shown to have the potential to transmit the South American type of myxoma virus. Following infection with the South American strain (Lausanne, Lu), S. nuttallii developed both a local lesion and secondary lesions on the skin. They did not develop the classical myxomatosis seen in European rabbits (Oryctolagus cuniculus). The infection at the inoculation site did not resolve during the 20-day time course of the trial and contained transmissible virus titres at all times. In contrast, S. audubonii infected with Lu had very few signs of disseminated infection and partially controlled virus replication at the inoculation site. The prototype Californian strain of myxoma virus (MSW) was able to replicate at the inoculation site of both species but did not induce clinical signs of a disseminated infection. In S. audubonii, there was a rapid response to MSW characterised by a massive T lymphocyte infiltration of the inoculation site by day 5. MSW did not reach transmissible titres at the inoculation site in either species. This might explain why the Californian myxoma virus has not expanded its host-range in North America. Crown Copyrigh