The role of Glycogen Synthase Kinase-3 in early embryonic stem cell differentiation

Embryonic stem cells, and the biochemical mechanisms underling their pluripotency has been the focus of intense research in recent years. Glycogen Synthase Kinase 3 (GSK3) has recently been implicated in a diverse array of cellular functions including embryonic stem cell pluipotency, and the aim of this thesis was to detail and investigate the regulation and role of GSK3 activity in controlling pluripotency and differentiation. This thesis has demonstrated that GSK3 kinase activity, normally considered constitutive, is suppressed in ES cells and is rapidly activated upon the commencement of difrerentiation. Activation of GSK3 enables phosphorylation and degradation of c-myc, which has been previously shown to be required for ES cell differentiation. Furthermore, this thesis presents evidence that GSK3 activity in ES cells may be regulated by subcellular translocation and phosphatases in response to signalling mediated by cellular attachment and other differentiation inducing events. A clearer understanding of the biology of pluripotent cells is necessary in order to better understand embryogenesis and the mechanisms of development, and to move towards the therapeutic potential of stem cells for use in cell based therapies. This study has added to our knowledge of GSK3 regulation with respect to its influence on the differentiation of embryonic stem cells.Thesis (M.Sc.) -- University of Adelaide, Dept. of Molecular and Biomedical Science, 200

Systematic review of nutritional interventions for people admitted to hospital for alcohol withdrawal

Aim: The aim of this review is to describe the nature of nutritional interventions for people admitted to hospital for alcohol withdrawal reported in the scientific literature and the health outcomes achieved. Methods: The review protocol was registered with PROSPERO (CRD42017081884). The following databases were systematically searched following the PRISMA protocol: CINAHL, MEDLINE, PsycARTICLES, PsycINFO, Scopus and Web of Science. Eligible studies were those published in English, in a hospital inpatient setting with the primary reason for admission being alcohol withdrawal. Studies of patient populations with the diagnosis of pancreatitis or liver cirrhosis were excluded. Studies were screened for eligibility, and data were extracted and descriptively analysed. Identified articles were assessed using the Quality Criteria Checklist for Primary Research produced by the Academy of Nutrition and Dietetics. Results: Fourteen studies met the inclusion criteria. Given the heterogeneity of studies, only a descriptive analysis of interventions could be achieved. Nutrition interventions included supplementation with thiamine, multivitamins, amino acids, antioxidant compounds, probiotics, magnesium or were educational interventions. Outcome measures included memory function, biochemical and anthropometrical indices, withdrawal symptoms, bowel flora levels and nutrition knowledge. However, the overall body of evidence was limited, particularly as there was a wide variation in participant age, study designs and duration of interventions. Conclusions: A wide range of nutrition interventions were identified, mostly involving nutrient supplements ameliorating inadequacies. Future research might also consider total dietary interventions as well as studies on the perspectives of people undergoing alcohol withdrawal

Reported behavioural differences between geldings and mares challenge sex-driven stereotypes in ridden equine behaviour

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Horse trainers and riders may have preconceived ideas of horse temperament based solely on the sex of the horse. A study (n = 1233) of horse enthusiasts (75% of whom had more than 8 years of riding experience) revealed that riders prefer geldings over mares and stallions. While these data may reflect different sex preferences in horses used for sport, they may also reduce the chances of some horses reaching their performance potential. Further, an unfounded sex prejudice is likely to contribute to unconscious bias when perceiving unwanted behaviours, simplistically attributing them to demographic characteristics rather than more complex legacies of training and prior learning. The current study analysed reported sex-related behavioural differences in ridden and non-ridden horses using data from responses to the pilot study of the Equine Behaviour Assessment and Research Questionnaire (E-BARQ) survey. Respondents (n = 1233) reported on the behaviour of their horse using a 151-item questionnaire. Data were searched for responses relating to mares and geldings, and 110 traits with the greatest percentage difference scores between mares and geldings were selected were tested for univariate significance at p < 0.2. Multivariable modelling of the effect of sex (mare or gelding) on remaining traits was assessed by ordinal logistic regression, using a cumulative proportional log odds model. Results revealed mares were significantly more likely to move away when being caught compared to geldings (p = 0.003). Geldings were significantly more likely to chew on lead ropes when tied (p = 0.003) and to chew on rugs (p = 0.024). However, despite sex-related differences in these non-ridden behaviours, there was no evidence of any significant sex-related differences in the behaviours of the horses when ridden. This finding suggests that ridden horse behaviour is not sexually dimorphic or that particular horse sports variously favour one sex over another

Reported Behavioural Differences between Geldings and Mares Challenge Sex-Driven Stereotypes in Ridden Equine Behaviour

Horse trainers and riders may have preconceived ideas of horse temperament based solely on the sex of the horse. A study (n = 1233) of horse enthusiasts (75% of whom had more than 8 years of riding experience) revealed that riders prefer geldings over mares and stallions. While these data may reflect different sex preferences in horses used for sport, they may also reduce the chances of some horses reaching their performance potential. Further, an unfounded sex prejudice is likely to contribute to unconscious bias when perceiving unwanted behaviours, simplistically attributing them to demographic characteristics rather than more complex legacies of training and prior learning. The current study analysed reported sex-related behavioural differences in ridden and non-ridden horses using data from responses to the pilot study of the Equine Behaviour Assessment and Research Questionnaire (E-BARQ) survey. Respondents (n = 1233) reported on the behaviour of their horse using a 151-item questionnaire. Data were searched for responses relating to mares and geldings, and 110 traits with the greatest percentage difference scores between mares and geldings were selected were tested for univariate significance at p \u3c 0.2. Multivariable modelling of the effect of sex (mare or gelding) on remaining traits was assessed by ordinal logistic regression, using a cumulative proportional log odds model. Results revealed mares were significantly more likely to move away when being caught compared to geldings (p = 0.003). Geldings were significantly more likely to chew on lead ropes when tied (p = 0.003) and to chew on rugs (p = 0.024). However, despite sex-related differences in these non-ridden behaviours, there was no evidence of any significant sex-related differences in the behaviours of the horses when ridden. This finding suggests that ridden horse behaviour is not sexually dimorphic or that particular horse sports variously favour one sex over another

Development and management of systemic lupus erythematosus in an HIV-infected man with hepatitis C and B co-infection following interferon therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>The association of human immunodeficiency virus and immune dysfunction leading to development of autoimmune markers is well described, but human immunodeficiency virus infection is relatively protective for the development of systemic lupus erythematosus. In contrast, development of systemic lupus erythematosus with hepatitis C and with interferon therapy is well described in a number of case reports. We here describe the first case of systemic lupus erythematosus developing in a man infected with human immunodeficiency virus, hepatitis C and hepatitis B co-infection where the onset seems to have been temporally related to interferon therapy.</p> <p>Case presentation</p> <p>We report the occurrence of systemic lupus erythematosus complicating interferon-α therapy for hepatitis C in a 47-year-old asplenic male with haemophilia co-infected with human immunodeficiency virus and hepatitis B. He presented with a truncal rash, abdominal pains and headache and later developed grade IV lupus nephritis requiring haemodialysis, mycophenolate mofetil and steroid therapy. We were able to successfully withdraw dialysis and mycophenolate while maintaining stable renal function.</p> <p>Conclusion</p> <p>Interferon-α is critical in antiviral immunity against hepatitis C but also acts as a pathogenic mediator for systemic lupus erythematosus, a condition associated with activation of plasmacytoid dendritic cells that are depleted in human immunodeficiency virus infection. The occurrence of auto-antibodies and lupus-like features in the coinfections with hepatitis C require careful assessment. Immunosuppressant therapy for lupus risks exacerbating underlying infections in patients with concurrent human immunodeficiency virus, hepatitis B and C.</p

‘Engage the World’: examining conflicts of engagement in public museums

Public engagement has become a central theme in the mission statements of many cultural institutions, and in scholarly research into museums and heritage. Engagement has emerged as the go-to-it-word for generating, improving or repairing relations between museums and society at large. But engagement is frequently an unexamined term that might embed assumptions and ignore power relationships. This article describes and examines the implications of conflicting and misleading uses of ‘engagement’ in relation to institutional dealings with contested questions about culture and heritage. It considers the development of an exhibition on the Dead Sea Scrolls by the Royal Ontario Museum, Toronto in 2009 within the new institutional goal to ‘Engage the World’. The chapter analyses the motivations, processes and decisions deployed by management and staff to ‘Engage the World’, and the degree to which the museum was able to re-think its strategies of public engagement, especially in relation to subjects,issues and publics that were more controversial in nature

Following the unusual breathing behaviour of 17O-enriched mixed-metal (Al,Ga)-MIL-53 using NMR crystallography

The authors would like to thank the ERC (EU FP7 Consolidator Grant 614290 EXONMR and Advanced Grant 787073 ADOR), and EPSRC (EP/N509759/1) for a studentship for CMR. SEA would like to thank the Royal Society and Wolfson Foundation for a merit award. We acknowledge support from the Collaborative Computational Project on NMR Crystallography (CCP-NC) funded by EPSRC (EP/M022501/1) and the UKCP consortium funded by EPSRC (EP/K013564/1). For computational resources we are grateful to the UK Materials and Molecular Modelling Hub, which is partially funded by EPSRC (EP/P020194/1) and the UK HPC Materials Chemistry Consortium, which is funded by EPSRC (EP/L000202). The research data (and/or materials) supporting this publication can be accessed at DOI: https://doi.org/10.17630/31529c8b-f197-484c-929b-ef993a5bea68.69The breathing behaviour of 17O-enriched (Al,Ga)-MIL-53, a terephthalate-based metal organic framework, has been investigated using a combination of solid-state nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction (PXRD) and first-principles calculations. These reveal that the behaviour observed for as-made, calcined, hydrated and subsequently dehydrated mixed-metal MIL-53 materials differs with composition, but cannot be described as the compositionally weighted average of the breathing behaviour seen for the two end members. Although the form of MIL-53 adopted by the as-made material is independent of metal composition, upon calcination, materials with higher levels of Al adopt an open pore (OP) form, as found for the Al end member, but substitution of Ga results in mixed pore materials, with OP and narrow pore (NP) forms co-existing. Although the Ga end member is prone to decomposition under the calcination conditions used, a low level of Al in the starting synthesis (5%) leads to an OP mixed-metal MOF that is stable to calcination. Upon hydration all materials almost exclusively adopt a closed pore (CP) structure, with strong hydrogen bonding interactions with water leading to two distinct resonances from the carboxylate oxygens in 17O NMR spectra. When dehydrated, different framework structures are found for the two end members, OP for Al- MIL-53 and NP for Ga-MIL-53, with the proportion of NP MOF seen to increase systematically with the Ga content in mixed-metal materials, in contrast to the forms seen upon initial calcination. 17O NMR spectra of mixed-metal MIL-53 materials show an increased preference for clustering of like cations as the Ga content increases. This is not a result of the small-scale dry gel conversion reactions used for enrichment, as a similar cation distribution and clustering is also observed for (Al0.5,Ga0.5)-MIL-53 synthesised hydrothermally and enriched with 17O via post-synthetic steaming.Publisher PDFPeer reviewe

Lean body mass associated with upper body strength in healthy older adults while higher body fat limits lower extremity performance and endurance

Impaired strength adversely influences an older person\u27s ability to perform activities of daily living. A cross-sectional study of 117 independently living men and women (age = 73.4 9.4 year; body mass index (BMI) = 27.6 4.8 kg/m2) aimed to assess the association between body composition and: (1) upper body strength (handgrip strength, HGS); (2) lower extremity performance (timed up and go (TUG) and sit to stand test (STS)); and (3) endurance (6-minute walk (SMWT). Body composition (% fat; lean body mass (LBM)) was assessed using bioelectrical impedance. Habitual physical activity was measured using the Minnesota Leisure Time Physical Activity Questionnaire (MLTPA) and dietary macronutrient intake, assessed using 24 h recalls and 3-day food records. Regression analyses included the covariates, protein intake (g/kg), MLTPA, age and sex. For natural logarithm (Ln) of right HGS, LBM (p \u3c 0.001) and % body fat (p \u3c 0.005) were significant (r2 = 46.5%; p \u3c 0.000). For left LnHGS, LBM (p \u3c 0.000), age (p = 0.036), protein intake (p = 0.015) and LnMLTPA (p = 0.015) were significant (r2 = 0.535; p \u3c 0.000). For SMW, % body fat, age and LnMLTPA were significant (r2 = 0.346; p \u3c 0.000). For STS, % body fat and age were significant (r2 = 0.251; p \u3c 0.000). LBM is a strong predictor of upper body strength while higher % body fat and lower physical activity are associated with poorer outcomes on tests of lower extremity performance

Left-handers look before they leap:handedness influences reactivity to novel Tower of Hanoi tasks

A sample of 203 task naïve left- and right-handed participants were asked to complete a combination of the 3- and 4-disk Towers of Hanoi (ToH), manipulating novelty and complexity. Self-reported state anxiety and latency to respond (initiation time) were recorded before each ToH. Novelty had a major effect on initiation time, particularly for left-handers. Left-handers had a longer latency to start and this was significantly longer on the first trial. Irrespective of hand-preference, initiation time reduced on the second trial, however, this was greatest for left-handers. Condition of task did not systematically influence initiation time for right handers, but did for left-handers. State anxiety was influenced by task novelty and complexity in a more complicated way. During the first trial, there was a significant handedness × number of disks interaction with left-handers having significantly higher state anxiety levels before the 3-disk ToH. This suggests that the initial reaction to this task for left-handers was not simply due to perceived difficulty. On their second trial, participants completing a novel ToH had higher state anxiety scores than those completing a repeated version. Overall, left-handers had a larger reduction in their state anxiety across trials. Relating to this, the expected strong positive correlation between state and trait anxiety was absent for left-handed females in their first tower presentation, but appeared on their second. This was driven by low trait anxiety individuals showing a higher state anxiety response in the first (novel) trial, supporting the idea that left-handed females respond to novelty in a way that is not directly a consequence of their trait anxiety. A possible explanation may be stereotype threat influencing the behavior of left-handed females