Observations on the mating behaviour of rams

TO work efficiently in commercial flocks, rams must mate with and fertilise relatively large numbers of ewes, often over short periods of mating. The importance of mating behaviour is obvious. Despite this, little is known of the mating behaviour of rams under commercial situations. A series of experiments in 1968 at Badgingarra Research Station was designed to investigate this and other aspects of mating behaviour

Clustered Computing for Political Science

http://deepblue.lib.umich.edu/bitstream/2027.42/116267/1/tpm04.pd

Piloting a manualised weight management programme (Shape Up-LD) for overweight and obese persons with mild-moderate learning disabilities: study protocol for a pilot randomised controlled trial

National obesity rates have dramatically risen over the last decade. Being obese significantly reduces life expectancy, increases the risk of a range of diseases, and compromises quality of life. Costs to both the National Health Service and society are high. An increased prevalence of obesity in people with learning disabilities has been demonstrated. The consequences of obesity are particularly relevant to people with learning disabilities who are already confronted by health and social inequalities. In order to provide healthcare for all, and ensure equality of treatment for people with learning disabilities, services must be developed specifically with this population in mind. The aim of this project is to pilot the evaluation of a manualised weight management programme for overweight and obese persons with mild-moderate learning disabilities (Shape Up-LD)

The Western Australian Clinical Senate as a Model for State-Wide Clinical Engagement

International reforms in healthcare have established the principal that embracing clinical engagement can drive healthcare reform and improved safety and quality outcomes. Most attention has focussed on how clinicians might be engaged at a local or hospital level. However, healthcare reforms are usually initiated at a state or national level. Less attention has gone into exploring the key elements of a model to achieve clinical engagement at state or national level. This paper explores the key elements of a successful state-wide clinical engagement model including culture and leadership, membership, decision-making processes and accountability and discusses how the current model of the Western Australian Clinical Senate addresses these elements. This model may be applicable in other jurisdictions and healthcare systems

The protein kinase C inhibitor, Ro-31-7459, is a potent activator of ERK and JNK MAP kinases in HUVECs and yet inhibits cyclic AMP-stimulated <i>SOCS-3</i> gene induction through inactivation of the transcription factor c-Jun

Induction of the suppressor of cytokine signalling 3 (SOCS-3) gene is vital to the normal control of inflammatory signalling. In order to understand these processes we investigated the role of the proto-oncogene component of the AP-1 transcription factor complex, c-Jun, in the regulation of SOCS-3 gene induction. We found that cyclic AMP stimulation of HUVECs promoted phosphorylation and activation of JNK MAP kinase and its substrate c-Jun. The JNK responsive element of the human SOCS-3 promoter mapped to a putative AP-1 site within 1000 bp of the transcription start site. The PKC inhibitors, GF-109203X, Gö-6983 and Ro-317549, were all found to inhibit AP-1 transcriptional activity, transcriptional activation of this minimal SOCS-3 promoter and SOCS-3 gene induction in HUVECs. Interestingly, Ro-317549 treatment was also found to promote PKC-dependent activation of ERK and JNK MAP kinases and promote JNK-dependent hyper-phosphorylation of c-Jun, whereas GF-109203X and Gö-6983 had little effect. Despite this, all three PKC inhibitors were found to be effective inhibitors of c-Jun DNA-binding activity. The JNK-dependent hyper-phosphorylation of c-Jun in response to Ro-317549 treatment of HUVECs does therefore not interfere with its ability to inhibit c-Jun activity and acts as an effective inhibitor of c-Jun-dependent SOCS-3 gene induction

Amplified Sediment waves in the Irish Sea (AmSedIS)

Exceptionally high, straight-crested and trochoidal sediment waves have recently been observed on shelf seas world-wide, and reach heights of up to 36 m in the Irish Sea. It is uncertain how the interplay between geological, biogeochemical and hydrodynamic processes influences the migration and extreme growth of these sediment waves. The AmSedIS project thus sets out to (1) investigate the role of sediment granulometry and sedimentavailability on both “extreme” and “normal” sediment wave development and (2) investigate the potential association of methane derived carbonate formation with extreme sediment wave growth. The preliminary findings are: (1) The crests of unusually high and trochoidal sediment waves still migrate over several meters per year and they consist of coarser, more poorly sorted sediments in comparison to the "normal" sediments waves; (2) Methane seepage is not considered a factor in extreme sediment wave development; (3) The excess of mobile sediment supply seems to allow for "extreme" sediment wave growth, and is linked to palaeo-tunnel valleys and the finer sediments that fill them or with converging sediment transport pathways; (4) The variation in sediment from sediment wave trough to crest to trough will form the basis for more advanced numerical modelling

High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability

Cancer stem cells (CSCs) have recently been identified in leukaemia and solid tumours; however, the role of CSCs in metastasis remains poorly understood. This dearth of knowledge about CSCs and metastasis is due largely to technical challenges associated with the use of primary human cancer cells in pre-clinical models of metastasis. Therefore, the objective of this study was to develop suitable pre-clinical model systems for studying stem-like cells in breast cancer metastasis, and to test the hypothesis that stem-like cells play a key role in metastatic behaviour. We assessed four different human breast cancer cell lines (MDA-MB-435, MDA-MB-231, MDA-MB-468, MCF-7) for expression of prospective CSC markers CD44/CD24 and CD133, and for functional activity of aldehyde dehydrogenase (ALDH), an enzyme involved in stem cell self-protection. We then used fluorescence-activated cell sorting and functional assays to characterize differences in malignant/metastatic behaviour in vitro (proliferation, colony-forming ability, adhesion, migration, invasion) and in vivo (tumorigenicity and metastasis). Sub-populations of cells demonstrating stem-cell-like characteristics (high expression of CSC markers and/or high ALDH) were identified in all cell lines except MCF-7. When isolated and compared to ALDHlowCD44low/- cells, ALDHhiCD44+CD24- (MDA-MB-231) and ALDHhiCD44+CD133+ (MDA-MB-468) cells demonstrated increased growth (P \u3c 0.05), colony formation (P \u3c 0.05), adhesion (P \u3c 0.001), migration (P \u3c 0.001) and invasion (P \u3c 0.001). Furthermore, following tail vein or mammary fat pad injection of NOD/SCID/IL2 gamma receptor null mice, ALDHhiCD44+CD24- and ALDHhiCD44+CD133+ cells showed enhanced tumorigenicity and metastasis relative to ALDHlowCD44low/- cells (P \u3c 0.05). These novel results suggest that stem-like ALDHhiCD44+CD24- and ALDHhiCD44+CD133+ cells may be important mediators of breast cancer metastasis

Segmenting excessive alcohol consumers : implications for social marketing

While extant studies have mainly investigated differences between drinkers and non-drinkers, the literature on segmenting heavy drinkers and profiling them is surprisingly scarce. This study makes a significant contribution to the social marketing literature by illustrating a novel way of targeting heavy drinkers by utilizing their health management styles and provides useful insights into understanding how segmentation could be a valuable tool for developing effective social marketing programmes that are aimed at reducing excessive alcohol consumption. Analysis of data collected through the HINTS study reveals a two-cluster segmentation model. The two segments of heavy drinkers distinctly differ in terms of the extent of reliance and trust they place on health service professionals. Hence, the segmentation analysis provides interesting and novel insights into the level of dependence of heavy drinkers on the health care system and their health management styles. The study provides an actionable perspective for future research, public policy and social marketing

Characterisation of small molecule ligands 4CMTB and 2CTAP as modulators of human FFA2 receptor signalling

© 2018, The Author(s). Short chain fatty acids (SCFAs) are protective against inflammatory diseases. Free fatty acid receptor 2 (FFA2), is a target of SCFAs however, their selectivity for FFA2 over other FFA receptors is limited. This study aimed to functionally characterise 2-(4-chlorophenyl)-3-methyl-N-(thiazole-2-yl)butanamide (4CMTB) and 4-((4-(2-chlorophenyl)thiazole-2-yl)amino)-4oxo-3-phenylbutanoic acid (2CTAP), and their enantiomers, in modulating FFA2 activity. The racemic mixture (R/S) and its constituents (R-) and (S-) 4CMTB or 2CTAP were used to stimulate human (h)FFA2 in the absence or presence of acetate. Calcium ions (Ca2+), phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) and cyclic adenosine monophosphate (cAMP) were measured. R/S-4CMTB is a functionally selective ago-allosteric ligand that enhances Ca2+ response to acetate. Both R/S-4CMTB and S-4CMTB are more potent activators of pERK1/2 and inhibitors of forskolin-induced cAMP than acetate. S-4CMTB increased neutrophil infiltration in intestinal ischemia reperfusion injury (IRI). 2CTAP inhibited constitutive Ca2+ levels, antagonised acetate-induced pERK1/2 and prevented damage following IRI. This study characterises enantiomers of functionally selective ligands for FFA2 in cells stably expressing hFFA2. It highlights the novel roles of selective FFA2 enantiomers 4CMTB and 2CTAP on Ca2+, pERK1/2 and cAMP and their roles as allosteric modulators which, may assist in efforts to design novel therapeutic agents for FFA2-driven inflammatory diseases

Mutations in topoisomerase IIβ result in a B cell immunodeficiency.

B cell development is a highly regulated process involving multiple differentiation steps, yet many details regarding this pathway remain unknown. Sequencing of patients with B cell-restricted immunodeficiency reveals autosomal dominant mutations in TOP2B. TOP2B encodes a type II topoisomerase, an essential gene required to alleviate topological stress during DNA replication and gene transcription, with no previously known role in B cell development. We use Saccharomyces cerevisiae, and knockin and knockout murine models, to demonstrate that patient mutations in TOP2B have a dominant negative effect on enzyme function, resulting in defective proliferation, survival of B-2 cells, causing a block in B cell development, and impair humoral function in response to immunization