Maintaining muscle mass during extended disuse: aestivating frogs as a model species

Prolonged muscle disuse in vertebrates can lead to a pathological change resulting in muscle wasting and a loss of muscle strength. In this paper, we review muscle disuse atrophy in the vertebrates and examine the factors that influence the magnitude of the atrophic response during extended periods of inactivity, both artificially imposed (e.g. limb immobilisation) and naturally occurring, such as the quiescence associated with dormancy (e.g. hibernation and aestivation). The severity of muscle atrophy is positively correlated with mass-specific metabolic rate, and the metabolic depression that occurs during dormancy would appear to have a protective role, reducing or preventing muscle atrophy despite periods of inactivity lasting 6-9 months. In the light of these findings, the role of reactive oxygen species and antioxidants during muscle disuse is emphasised

Progesterone signalling in broiler skeletal muscle is associated with divergent feed efficiency

Background: We contrast the pectoralis muscle transcriptomes of broilers selected from within a single genetic line expressing divergent feed efficiency (FE) in an effort to improve our understanding of the mechanistic basis of FE. Results: Application of a virtual muscle model to gene expression data pointed to a coordinated reduction in slow twitch muscle isoforms of the contractile apparatus (MYH15, TPM3, MYOZ2, TNNI1, MYL2, MYOM3, CSRP3, TNNT2), consistent with diminishment in associated slow machinery (myoglobin and phospholamban) in the high FE animals. These data are in line with the repeated transition from red slow to white fast muscle fibres observed in agricultural species selected on mass and FE. Surprisingly, we found that the expression of 699 genes encoding the broiler mitoproteome is modestly–but significantly–biased towards the high FE group, suggesting a slightly elevated mitochondrial content. This is contrary to expectation based on the slow muscle isoform data and theoretical physiological capacity arguments. Reassuringly, the extreme 40 most DE genes can successfully cluster the 12 individuals into the appropriate FE treatment group. Functional groups contained in this DE gene list include metabolic proteins (including opposing patterns of CA3 and CA4), mitochondrial proteins (CKMT1A), oxidative status (SEPP1, HIG2A) and cholesterol homeostasis (APOA1, INSIG1). We applied a differential network method (Regulatory Impact Factors) whose aim is to use patterns of differential co-expression to detect regulatory molecules transcriptionally rewired between the groups. This analysis clearly points to alterations in progesterone signalling (via the receptor PGR) as the major driver. We show the progesterone receptor localises to the mitochondria in a quail muscle cell line. Conclusions: Progesterone is sometimes used in the cattle industry in exogenous hormone mixes that lead to a ~20% increase in FE. Because the progesterone receptor can localise to avian mitochondria, our data continue to point to muscle mitochondrial metabolism as an important component of the phenotypic expression of variation in broiler FE

An Always Correlated gene expression landscape for ovine skeletal muscle, lessons learnt from comparison with an “equivalent” bovine landscape

BACKGROUND: We have recently described a method for the construction of an informative gene expression correlation landscape for a single tissue, longissimus muscle (LM) of cattle, using a small number (less than a hundred) of diverse samples. Does this approach facilitate interspecies comparison of networks? FINDINGS: Using gene expression datasets from LM samples from a single postnatal time point for high and low muscling sheep, and from a developmental time course (prenatal to postnatal) for normal sheep and sheep exhibiting the Callipyge muscling phenotype gene expression correlations were calculated across subsets of the data comparable to the bovine analysis. An “Always Correlated” gene expression landscape was constructed by integrating the correlations from the subsets of data and was compared to the equivalent landscape for bovine LM muscle. Whilst at the high level apparently equivalent modules were identified in the two species, at the detailed level overlap between genes in the equivalent modules was limited and generally not significant. Indeed, only 395 genes and 18 edges were in common between the two landscapes. CONCLUSIONS: Since it is unlikely that the equivalent muscles of two closely related species are as different as this analysis suggests, within tissue gene expression correlations appear to be very sensitive to the samples chosen for their construction, compounded by the different platforms used. Thus users need to be very cautious in interpretation of the differences. In future experiments, attention will be required to ensure equivalent experimental designs and use cross-species gene expression platform to enable the identification of true differences between different species

Seasonal resource selection of an arboreal habitat specialist in a human-dominated landscape: a case study using red panda

Human-dominated landscapes provide heterogeneous wildlife habitat. Conservation of habitat specialists, like red pandas Ailurus fulgens, inhabiting such landscapes is challenging. Therefore, information on resource use across spatial and temporal scales could enable informed-decision making with better conservation outcomes. We aimed to examine the effect of geo-physical, vegetation, and disturbance variables on fine-scale habitat selection of red pandas in one such landscape. We equipped 10 red pandas with GPS collars in eastern Nepal in 2019 and monitored them for 1 year. Our analysis was based on a generalized-linear-mixed model. We found the combined effect of geo-physical, vegetation, and disturbance variables resulted in differences in resource selection of red pandas and that the degree of response to these variables varied across seasons. Human disturbances, especially road and cattle herding activities, affected habitat utilization throughout the year whereas other variables were important only during restricted periods. For instance, geo-physical variables were influential in the premating and cub-rearing seasons while vegetation variables were important in all seasons other than premating. Red pandas selected steeper slopes with high solar insolation in the premating season while they occupied elevated areas and preferred specific aspects in the cub-rearing season. Furthermore, the utilized areas had tall bamboo in the birthing and cub-rearing seasons while they also preferred diverse tree species and high shrub cover in the latter. Our study demonstrates the significance of season-specific management, suggests the importance of specific types of vegetation during biologically crucial periods, and emphasizes the necessity to minimize disturbances throughout the year

Comparing plasma and faecal measures of steroid hormones in Adelie penguins Pygoscelis adeliae

Physiological measurements of both stress and sex hormones are often used to estimate the consequences of natural or human-induced change in ecological studies of various animals. Different methods of hormone measurement exist, potentially explaining variation in results across studies; methods should be cross-validated to ensure that they correlate. We directly compared faecal and plasma hormone measurements for the first time in a wild free-living species, the Adelie penguin (Pygoscelis adeliae). Blood and faecal samples were simultaneously collected from individual penguins for comparison and assayed for testosterone and corticosterone (or their metabolites). Sex differences and variability within each measure, and correlation of values across measures were compared. For both hormones, plasma samples showed greater variation than faecal samples. Males had higher mean corticosterone concentrations than females, but the difference was only statistically significant in faecal samples. Plasma testosterone, but not faecal testosterone, was significantly higher in males than females. Correlation between sample types was poor overall, and weaker in females than in males, perhaps because measures from plasma represent hormones that are both free and bound to globulins, whereas measures from faeces represent only the free portion. Faecal samples also represent a cumulative measure of hormones over time, as opposed to a plasma ‘snapshot’ concentration. Our data indicate that faecal sampling appears more suitable for assessing baseline hormone concentrations, whilst plasma sampling may best define immediate responses to environmental events. Consequently, future studies should ensure that they select the most appropriate matrix and method of hormone measurement to answer their research questions

Gene expression studies of developing bovine longissimus muscle from two different beef cattle breeds

Background: The muscle fiber number and fiber composition of muscle is largely determined during prenatal development. In order to discover genes that are involved in determining adult muscle phenotypes, we studied the gene expression profile of developing fetal bovine longissimus muscle from animals with two different genetic backgrounds using a bovine cDNA microarray. Fetal longissimus muscle was sampled at 4 stages of myogenesis and muscle maturation: primary myogenesis (d 60), secondary myogenesis (d 135), as well as beginning (d 195) and final stages (birth) of functional differentiation of muscle fibers. All fetuses and newborns (total n = 24) were from Hereford dams and crossed with either Wagyu (high intramuscular fat) or Piedmontese (GDF8 mutant) sires, genotypes that vary markedly in muscle and compositional characteristics later in postnatal life. Results: We obtained expression profiles of three individuals for each time point and genotype to allow comparisons across time and between sire breeds. Quantitative reverse transcription-PCR analysis of RNA from developing longissimus muscle was able to validate the differential expression patterns observed for a selection of differentially expressed genes, with one exception. We detected large-scale changes in temporal gene expression between the four developmental stages in genes coding for extracellular matrix and for muscle fiber structural and metabolic proteins. FSTL1 and IGFBP5 were two genes implicated in growth and differentiation that showed developmentally regulated expression levels in fetal muscle. An abundantly expressed gene with no functional annotation was found to be developmentally regulated in the same manner as muscle structural proteins. We also observed differences in gene expression profiles between the two different sire breeds. Wagyu-sired calves showed higher expression of fatty acid binding protein 5 (FABP5) RNA at birth. The developing longissimus muscle of fetuses carrying the Piedmontese mutation shows an emphasis on glycolytic muscle biochemistry and a large-scale up-regulation of the translational machinery at birth. We also document evidence for timing differences in differentiation events between the two breeds. Conclusion: Taken together, these findings provide a detailed description of molecular events accompanying skeletal muscle differentiation in the bovine, as well as gene expression differences that may underpin the phenotype differences between the two breeds. In addition, this study has highlighted a non-coding RNA, which is abundantly expressed and developmentally regulated in bovine fetal muscle

Electrolyte effects on poly (acrylic acid)-based aircraft de-icing fluids

Poly (acrylic acid) [PAA]-based aircraft de-icing fluids are widely used commercially but are known to be subject to the formation of insoluble gel particles within wing structures. In this study, the rheological effects of the sodium chloride, potassium formate, and calcium acetate with commercially used PAA-based fluids are reported across the temperature range of −15 to 15 °C. Calcium ions have the potential to create gel particles, reflected in the shifts in the viscosity–temperature profile, while PAA aggregation is influenced by the concentrations and compositions of sodium and potassium salts in the water used for dilution. From the data presented, it is possible to create de-icing fluid formulations with the necessary rheological characteristics from stock solutions by dilution using available water sources, providing that the ion concentration is known

A haplotype information theory method reveals genes of evolutionary interest in European vs. Asian pigs

Asian and European wild boars were independently domesticated ca. 10,000 years ago. Since the 17th century, Chinese breeds have been imported to Europe to improve the genetics of European animals by introgression of favourable alleles, resulting in a complex mosaic of haplotypes. To interrogate the structure of these haplotypes further, we have run a new haplotype segregation analysis based on information theory, namely compression efficiency (CE). We applied the approach to sequence data from individuals from each phylogeographic region (n = 23 from Asia and Europe) including a number of major pig breeds. Our genome-wide CE is able to discriminate the breeds in a manner reflecting phylogeography. Furthermore, 24,956 non-overlapping sliding windows (each comprising 1,000 consecutive SNP) were quantified for extent of haplotype sharing within and between Asia and Europe. The genome-wide distribution of extent of haplotype sharing was quite different between groups. Unlike European pigs, Asian pigs haplotype sharing approximates a normal distribution. In line with this, we found the European breeds possessed a number of genomic windows of dramatically higher haplotype sharing than the Asian breeds. Our CE analysis of sliding windows capture some of the genomic regions reported to contain signatures of selection in domestic pigs. Prominent among these regions, we highlight the role of a gene encoding the mitochondrial enzyme LACTB which has been associated with obesity, and the gene encoding MYOG a fundamental transcriptional regulator of myogenesis. The origin of these regions likely reflects either a population bottleneck in European animals, or selective targets on commercial phenotypes reducing allelic diversity in particular genes and/or regulatory regions

Space use, interaction and recursion in a solitary specialized herbivore: a red panda case study

Better understanding of ecology is crucial for the success of an endangered species conservation program. There is little information available on space use, conspecific interactions and recursions by one such species, the red panda Ailurus fulgens. To address this deficiency we used GPS telemetry to examine their home range, core area, home-range overlap, dynamic interactions, and recursive movement, and investigated the effect of sex, age, and body mass on these behaviours across seasons. The median annual home range was 1.41 with nearly a quarter of this range being used as the core area. Sex and reproductive status were the key determinants of space use patterns on a seasonal scale, while body mass and age remained significant correlates for the core area. The home range of males was nearly double that of females, likely because of the polygynous mating system in red pandas. Females avoided overlapping home ranges while males overlapped home range with up to four females, and neighbouring males overlapped nearly half of their ranges. We found rare interactions between males and females outside the mating season. Red pandas showed site fidelity within their territory with seasonal variation across sex classes. We also observed high individual variation in patterns of both space use and recursion. Taken together, these results suggest that differences in biological requirements across seasons determine red panda space use patterns, conspecific interactions and recursion. But forage availability and quality, climatic factors, disturbances and habitat fragmentation are also likely to influence these behaviours, and these need to be investigated

The Efficacy of Sunitinib Treatment of Renal Cancer Cells Is Associated with the Protein PHAX In Vitro

Anti-angiogenic agents, such as the multi-tyrosine kinase inhibitor sunitinib, are key first line therapies for metastatic clear cell renal cell carcinoma (ccRCC), but their mechanism of action is not fully understood. Here, we take steps towards validating a computational prediction based on differential transcriptome network analysis that phosphorylated adapter RNA export protein (PHAX) is associated with sunitinib drug treatment. The regulatory impact factor differential network algorithm run on patient tissue samples suggests PHAX is likely an important regulator through changes in genome-wide network connectivity. Immunofluorescence staining of patient tumours showed strong localisation of PHAX to the microvasculature consistent with the anti-angiogenic effect of sunitinib. In normal kidney tissue, PHAX protein abundance was low but increased with tumour grade (G1 vs. G3/4; p 0.01), consistent with a possible role in cancer progression. In organ culture, ccRCC cells had higher levels of PHAX protein expression than normal kidney cells, and sunitinib increased PHAX protein expression in a dose dependent manner (untreated vs. 100 µM; p 0.05). PHAX knockdown in a ccRCC organ culture model impacted the ability of sunitinib to cause cancer cell death (p 0.0001 untreated vs. treated), suggesting a role for PHAX in mediating the efficacy of sunitinib