Merino ewes that are genetically fatter lose less weight when nutrition is restricted

Ewes that lose less weight when there is a shortage of paddock feed are potentially more profitable because they require less supplementary feeding or can be grazed at higher stocking rates during autumn/winter (Young et al. 2011). Adams et al. (2006) have shown that sheep genotypes which lose more weight when underfed have lower metabolic reserves including fat. This paper tested the hypothesis that selection for increased fatness would reduce the rate of liveweight loss in adult Merino ewes when nutrition was restricted

Whole-body fatness is a good predictor of phenotypic feed and liveweight efficiency in adult Merino ewes fed a poor-quality diet

Weight loss due to poor nutrition in adult ewes over summer-autumn is economically expensive due to immediate costs such as feed and labour but also due to ongoing costs to reproductive success and ewe health. We predicted that adult Merino ewes with a higher proportion of fat would be more efficient, both through lower intake and reduced weight loss. Four-year-old Merino ewes (n ≤ 64) were held in single pens and fed a chaff-based diet either ad libitum, with the aim of achieving liveweight maintenance, or a restricted amount to achieve liveweight loss of 100 g/day. Liveweight change and feed intake were measured, and residual liveweight change and residual feed intake were used to indicate efficiency. There was a difference of 2 MJ of metabolisable energy per day between the most efficient and least efficient ewes for residual feed intake, and a difference of 90 g per day between the most efficient and least efficient ewes for residual liveweight change. There was a significant association between blood plasma concentrations of leptin and both liveweight and feed efficiency, so that ewes with high concentrations of leptin had a lower daily intake, and/or lost less weight than did those with low concentrations of leptin. Managing adult Merino ewes to maximise fat-tissue accretion during spring via genetics and/or nutritional management could be a useful strategy to reduce feed requirements during summer-autumn because the ewes will be more efficient and have larger fat reserves to lose before achieving a lower critical limit

Applications of proxy system modeling in high resolution paleoclimatology

AbstractA proxy system model may be defined as the complete set of forward and mechanistic processes by which the response of a sensor to environmental forcing is recorded and subsequently observed in a material archive. Proxy system modeling complements and sharpens signal interpretations based solely on statistical analyses and transformations; provides the basis for observing network optimization, hypothesis testing, and data-model comparisons for uncertainty estimation; and may be incorporated as weak but mechanistically-plausible constraints into paleoclimatic reconstruction algorithms. Following a review illustrating these applications, we recommend future research pathways, including development of intermediate proxy system models for important sensors, archives, and observations; linking proxy system models to climate system models; hypothesis development and evaluation; more realistic multi-archive, multi-observation network design; examination of proxy system behavior under extreme conditions; and generalized modeling of the total uncertainty in paleoclimate reconstructions derived from paleo-observations

Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma

Malignant mesothelioma is an aggressive and often fatal cancer associated with asbestos exposure. The disease originates in the mesothelial lining of the serosal cavities, most commonly affecting the pleura. Survival rates are low as diagnosis often occurs at an advanced stage and current treatments are limited. Identifying new diagnostic and therapeutic targets for mesothelioma remains a priority, particularly for the new wave of victims exposed to asbestos through do-it-yourself renovations and in countries where asbestos is still mined and used. Recent advances have demonstrated a biological role for the small but powerful gene regulators microRNA (miRNA) in mesothelioma. A number of potential therapeutic targets have been identified. MiRNA have also become popular as potential biomarkers for mesothelioma due to their stable expression in bodily fluid and tissues. In this review, we highlight the current challenges associated with the diagnosis and treatment of mesothelioma and discuss how targeting miRNA may improve diagnostic, prognostic and therapeutic approaches

Genetic fat – bullet proofing the Merino ewe

Merino ewes are the backbone of the Australian sheep industry and this is likely to be the case for some time. Stocking rate will remain a key profit driver in Merino enterprises and to maintain or improve profitability producers will need to continually adapt their production systems to deal with even larger changes in feed supply between seasons and years. The reproductive performance of the Merino ewe also needs to improve, largely through improving the survival of twin born lambs, to rebuild flock numbers and meet market demand for lamb and sheep meat. Increasing both stocking rates and reproductive performance need to be achieved in the context of producers wanting to run more sheep per person with less intervention and increased consumer demand for welfare friendly products. Improving genetics and matching sheep genotype to the production and management system will inevitably become more important. We believe this will include defining traits to more easily identify Merino sheep that are more robust, that lose less liveweight when faced with sub-optimum nutrition and that produce more progeny with higher survival rates both pre- and post-weaning. Increasing genetic fat is the prime candidate for increasing the robustness of Merino ewes and their progeny as the storage and mobilisation of fat is an important mechanism for all animals to cope with fluctuating environments. Fat is stored during favourable times and then mobilised to provide energy for fundamental functions when requirements exceed supply, such as during periods of limited nutrition or during late pregnancy and lactation. The amount of fat stored in fat depots in sheep can be increased by selection for higher subcutaneous fat depth, using Australian Sheep Breeding Values (ASBVs) from MERINOSELECT. However, from a genetic perspective, reducing the fatness of lamb to improve its appeal to the consumer has resulted in a general focus on selection for less fat in Australian sheep breeds. Merino sheep have also become leaner as a result of selection for higher fleece weights and the genetic association between higher fleece weight and reduced fatness (Huisman and Brown 2009). Defining the true value of fat requires an understanding of the effect it has on the value of lamb carcasses as well as its effects on the productivity of the sheep production system in different environments. In this paper we have reviewed published papers and our own unpublished work to test the hypothesis that Merino sheep that are genetically fatter will have improved performance especially under more restricted nutritional conditions

Physics of Eclipsing Binaries: Heartbeat Stars and Tidally Induced Pulsations

Heartbeat stars are a relatively new class of eccentric ellipsoidal variable first discovered by Kepler. An overview of the current field is given with details of some of the interesting objects identified in our current Kepler sample of 135 heartbeats stars. Three objects that have recently been or are undergoing detailed study are described along with suggestions for further avenues of research. We conclude by discussing why heartbeat stars are an interesting new tool to study tidally induced pulsations and orbital dynamics

Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis

Gli transcription factors of the Hedgehog (Hh) pathway have been reported to be drivers of malignant mesothelioma (MMe) cell survival. The Gli inhibitor GANT61 induces apoptosis in various cancer cell models, and has been associated directly with Gli inhibition. However various chemotherapeutics can induce cell death through generation of reactive oxygen species (ROS) but whether ROS mediates GANT61-induced apoptosis is unknown. In this study human MMe cells were treated with GANT61 and the mechanisms regulating cell death investigated. Exposure of MMe cells to GANT61 led to G1 phase arrest and apoptosis, which involved ROS but not its purported targets, GLI1 or GLI2. GANT61 triggered ROS generation and quenching of ROS protected MMe cells from GANT61-induced apoptosis. Furthermore, we demonstrated that mitochondria are important in mediating GANT61 effects: (1) ROS production and apoptosis were blocked by mitochondrial inhibitor rotenone; (2) GANT61 promoted superoxide formation in mitochondria; and (3) mitochondrial DNA-deficient LO68 cells failed to induce superoxide, and were more resistant to apoptosis induced by GANT61 than wild-type cells. Our data demonstrate for the first time that GANT61 induces apoptosis by promoting mitochondrial superoxide generation independent of Gli inhibition, and highlights the therapeutic potential of mitochondrial ROS-mediated anticancer drugs in MMe

Mutational Analysis of Hedgehog Signaling Pathway Genes in Human Malignant Mesothelioma

Background The Hedgehog (HH) signaling pathway is critical for embryonic development and adult homeostasis. Recent studies have identified regulatory roles for this pathway in certain cancers with mutations in the HH pathway genes. The extent to which mutations of the HH pathway genes are involved in the pathogenesis of malignant mesothelioma (MMe) is unknown. Methodology/Principal Findings Real-time PCR analysis of HH pathway genes PTCH1, GLI1 and GLI2 were performed on 7 human MMe cell lines. Exon sequencing of 13 HH pathway genes was also performed in cell lines and human MMe tumors. In silico programs were used to predict the likelihood that an amino-acid substitution would have a functional effect. GLI1, GLI2 and PTCH1 were highly expressed in MMe cells, indicative of active HH signaling. PTCH1, SMO and SUFU mutations were found in 2 of 11 MMe cell lines examined. A non-synonymous missense SUFU mutation (p.T411M) was identified in LO68 cells. In silico characterization of the SUFU mutant suggested that the p.T411M mutation might alter protein function. However, we were unable to demonstrate any functional effect of this mutation on Gli activity. Deletion of exons of the PTCH1 gene was found in JU77 cells, resulting in loss of one of two extracellular loops implicated in HH ligand binding and the intracellular C-terminal domain. A 3-bp insertion (69_70insCTG) in SMO, predicting an additional leucine residue in the signal peptide segment of SMO protein was also identified in LO68 cells and a MMe tumour. Conclusions/Significance We identified the first novel mutations in PTCH1, SUFU and SMO associated with MMe. Although HH pathway mutations are relatively rare in MMe, these data suggest a possible role for dysfunctional HH pathway in the pathogenesis of a subgroup of MMe and help rationalize the exploration of HH pathway inhibitors for MMe therapy

A Parametric Study of Erupting Flux Rope Rotation. Modeling the "Cartwheel CME" on 9 April 2008

The rotation of erupting filaments in the solar corona is addressed through a parametric simulation study of unstable, rotating flux ropes in bipolar force-free initial equilibrium. The Lorentz force due to the external shear field component and the relaxation of tension in the twisted field are the major contributors to the rotation in this model, while reconnection with the ambient field is of minor importance. Both major mechanisms writhe the flux rope axis, converting part of the initial twist helicity, and produce rotation profiles which, to a large part, are very similar in a range of shear-twist combinations. A difference lies in the tendency of twist-driven rotation to saturate at lower heights than shear-driven rotation. For parameters characteristic of the source regions of erupting filaments and coronal mass ejections, the shear field is found to be the dominant origin of rotations in the corona and to be required if the rotation reaches angles of order 90 degrees and higher; it dominates even if the twist exceeds the threshold of the helical kink instability. The contributions by shear and twist to the total rotation can be disentangled in the analysis of observations if the rotation and rise profiles are simultaneously compared with model calculations. The resulting twist estimate allows one to judge whether the helical kink instability occurred. This is demonstrated for the erupting prominence in the "Cartwheel CME" on 9 April 2008, which has shown a rotation of \approx 115 degrees up to a height of 1.5 R_sun above the photosphere. Out of a range of initial equilibria which include strongly kink-unstable (twist Phi=5pi), weakly kink-unstable (Phi=3.5pi), and kink-stable (Phi=2.5pi) configurations, only the evolution of the weakly kink-unstable flux rope matches the observations in their entirety.Comment: Solar Physics, submitte