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    Acceptability of LGBTQ-Affirmative Cognitive Behavioral Group Therapy for Youth: Results from a Pilot Study
    (2023-04-01) Seager van Dyk I; Layland EK; Soulliard ZA; Pachankis JE
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    A genetic approach to identify amino acids in Gcn1 required for Gcn2 activation
    (2022-09-08) Schiemann A; Gottfried S; Sattlegger E
    The General Amino Acid Control stress signalling pathway allows cells to sense and overcome starvation. One of the major players in this pathway is the protein kinase Gcn2 found in all eukaryotic cells. Activation of Gcn2 leads to phosphorylation of the alpha subunit of eukaryotic translation initiation factor (eIF2α), which then leads to the re-programming of the cell’s gene transcription and translation profile, and ultimately allowing cells to cope with and overcome starvation. For sensing starvation, Gcn2 must directly bind to its effector protein Gcn1. This interaction is mediated via a region in Gcn1 called the RWD binding domain (RWDBD). Overexpression of the RWDBD alone impairs Gcn2 activation through disrupting endogenous Gcn1-Gcn2 interaction, hampering eIF2α phosphorylation, and consequently cells cannot overcome starvation and fail to grow.  This dominant negative phenotype is dependent on Arg-2259 in RWDBD.  Taking advantage of this phenotype in yeast, we here found that the dominant negative phenotype was reverted by each of four amino acid substitutions, K2270A, R2289A, R2297A, and K2301A.  This correlated with increased eIF2α phosphorylation levels, suggesting their relevance for Gcn2 activation.  All but Lys-2270 are fully surface exposed, suggesting that these amino acids may directly contact Gcn2.  We also found amino acid substitutions that enhanced the dominant negative phenotype of the overexpressed RWDBD, and correlated with further reduction in eIF2α-P levels.  Our findings suggest that two helices in Gcn1 constitute at least one Gcn2 contact point.
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    Why so unfit?: Assessing potential barriers to exercise adoption in middle-aged men
    (The Author(s), 2005-02-10) Towers AJ; Flett RA; Seebeck RF; Towers, AJ; Flett, RA; Seebeck, RF
    Compared to women, men:  have a higher mortality rate  consistently die younger  are more susceptible to sedentary-lifestyle related diseases (e.g., cardiovascular disease)  are more likely to engage in behaviours that increase risk of injury, disease, or death  are less likely to seek help with physical health. Despite these statistics, the amount of literature devoted to women’s health in the past two decades still greatly exceeds that devoted to men’s health. The result is that we actually know very little about what influences men’s health behaviours. Introduction We utilised the transtheoretical model of exercise behaviour change to determine the pattern of exercise adoption in middle-aged men. We also analysed whether this pattern was influenced by three potential barriers to exercise: poor self-rated health, low levels of internal health locus of control, and high perceived stress levels. Hypotheses Compared to participants in the last stage of change (maintenance), it was hypothesised that participants in the first stage of exercise change (precontemplation) would have:  lower self-efficacy  less concern over the pros of exercise  more concern over the cons of exercise  poorer self-rated health  higher levels of perceived stress  lower levels of internal health locus of control [From Introduction]
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    Sensory acceptability and chemical characteristics of healthy rib-eye steaks from forage‐finished steers
    (2012-06-26) Torrico D; Jirangrat W; Scaglia G; Malekian F; Janes ME; McMillin KW; Prinyawiwatkul W
    Consumer interest in health benefits of forage-finished beef has led to increased product demand. To date, little information on sensory characteristics of cooked forage-finished beef is available. We evaluated sensory acceptability and chemical characteristics of rib-eye steaks from forage-finished steers. Rib-eye steaks from 3 forage-finished steers [S1 (bermudagrass+ryegrass, etc.); S2 (bermudagrass+ryegrass+berseem, etc.); S3 (bermudagrass+berseem+forage soybean+brown midrib sorghum, etc.)], and one C [commercial steak], cooked by grilling and/or 2-sided grilling, were evaluated for chemical composition and microbial safety. Sensory liking [overall-appearance (OAR) and fat-appearance (FA) for raw steaks; overall-appearance (OAC), overall-flavor (OF), juiciness, tenderness, and overall-liking (OL) for cooked steaks] were evaluated by 112 Hispanic consumers. Data were analyzed (PROC MIXED, a=0.05). C (raw) had higher fat (50.2% compared to 23.0-24.9%) and lower protein (49.4% compared to 73.5-74.4%, dry weight basis) contents compared with S1 and S2. S1 and S3 had higher omega-3 (0.49-0.55 compared to 0.09%), lower omega-6/omega-3 ratio (2.51-2.81 compared to 10.07), and lower PUFA (4.31-4.77 vs. 8.4%) contents than C, thus exhibiting a healthier fatty acid profile. Concerning raw steaks, S3 had higher OAR (6.9 compared to 5.4-5.9) and FA (5.9 compared to 4.9-5.1) liking scores than other samples. Purchase intent based on visual appearance was highest for S3 (85.7%). Concerning cooked steaks, the 2 cooking methods did not cause significant differences in liking scores. Juiciness and OL scores of C steaks (both cooking methods) and S3 (2-sided grilling) were not significantly different. Purchase intent (after health benefits of forage-finished steaks was informed) increased from 62.0-73.8 to 69.8-85.7%. The mean drop of liking scores was -1.00 to -2.50 and -0.50 to -2.50 on the 9-point OL scale, respectively, when cooked steaks were not-juicy-enough and not-tender-enough. Cooked and raw rib-eye steaks were free of E. coli . This study demonstrated that forage-finished steaks are healthier than grain-fed commercial steaks and have market potential toward Hispanic population.
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    sFlt-1 and NTproBNP independently predict mortality in a cohort of heart failure patients.
    (2018-12-02) Paterson MA; Pilbrow AP; Frampton CM; Cameron VA; Pemberton CJ; Lund M; Devlin GP; Doughty RN; Richards AM; Palmer B
    Objective: Soluble fms-like tyrosine kinase-1 (sFlt-1) is a circulating receptor for VEGF-A. Recent reports of elevated plasma levels of sFlt-1 in coronary heart disease and heart failure (HF) motivated our study aimed at investigating the utility of sFlt-1 as a prognostic biomarker in heart failure patients. Methods: ELISA assays for sFlt-1 and NTproBNP were performed in n=858 patients from a prospective multicentre, observational study (the PEOPLE study) of outcome among patients after appropriate treatment for an episode of acute decompensated HF in New Zealand. Plasma was sampled at a baseline visit and stored at -80°C. Statistical tests were adjusted for patient age at baseline visit, skewed data were log-adjusted and the endpoint for clinical outcome analysis was all-cause death. Patients were followed for a median of 3.63 (range 0.74-5.50) years. Results: Mean baseline plasma sFlt-1 was 125 +/- 2.01 pg/ml. sFlt-1 was higher in patients with HF with reduced ejection fraction (HFrEF) (130 +/- 2.62 pg/ml, n=553) compared to those with HF with preserved EF (HFpEF) (117 +/-3.59 pg/ml, n=305; p=0.005). sFlt-1 correlated with heart rate (r=0.148, p<0.001), systolic blood pressure (r=-0.139, p<0.001) and LVEF (r=-0.088, p=0.019). A Cox proportional hazards model showed sFlt-1 was a predictor of all-cause death (HR=6.30, p<0.001) in the PEOPLE cohort independent of age, NTproBNP, ischaemic aetiology, and NYHA class (n=842, 274 deaths), established predictors of mortality in the PEOPLE cohort. Conclusion: sFlt-1 levels at baseline should be investigated further as a predictor of death; complementary to established prognostic biomarkers in heart failure.
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    Combining Tn-seq with comparative genomics identifies proteins uniquely essential in Shigella flexneri
    (2015-09-03) Freed NE; Bumann D; Silander O
    Protein functions that are essential for the growth of bacterial pathogens provide promising targets for antibacterial treatment. This is especially true if those functions are uniquely essential for the pathogen, as this might allow the development of targeted antibiotics, i.e. those that disrupt essential functions only for the pathogenic bacteria. Here we present the results of a Tn-seq experiment designed to detect essential protein coding genes in Shigella flexneri 2a 2457T on a genome-wide scale. Our results suggest that 471 protein-coding genes in this organism are critical for cellular growth in rich media. Comparing this set of essential genes (the essential gene complement) with their orthologues in the closely related organism Escherichia coli K12 BW25113 revealed a significant number of genes that are essential in Shigella but not in E. coli, suggesting that the functional correspondence of these proteins had changed. Notably, we also identified a set of functionally related genes that are essential in Shigella but which have no orthologues in E. coli. We found an extreme bias in proteins that have evolved to provide essential functions, with many proteins essential in Shigella but not E. coli, but with none (or very few) being essential in E. coli but not Shigella. We also identify a set- of genes involved in nucleotide biosynthesis that are essential in Shigella, but which lack orthologues in E. coli. Consequently, the data presented here suggest that the essential gene complement can quickly become organism specific, especially for pathogenic organisms whose genomes might have reduced robustness in their metabolic capacity (e.g. functional redundancy), or a reduced numbers of protein coding genes. These results thus open the possibility of developing antibiotic treatments that target differentially essential genes, which may exist even between very closely related strains of bacteria.
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    Structural determination of archaeal UDP-N-acetylglucosamine 4-epimerase from Methanobrevibacter ruminantium M1 in complex with the bacterial cell wall intermediate UDP-N-acetylmuramic acid
    (2018-12-02) Carbone V; Schofield L; Sang C; Sutherland-Smith A; Ronimus RS
    The crystal structure of UDP-N-acetylglucosamine 4-epimerase (UDP-GlcNAc 4-epimerase; WbpP; EC 5.1.3.7), from the archaeal methanogen Methanobrevibacter ruminantium strain M1, was determined to a resolution of 1.65 Å. The structure, with a single monomer in the crystallographic asymmetric unit, contained a conserved N-terminal Rossmann fold for nucleotide binding and an active site positioned in the C-terminus. UDP-GlcNAc 4-epimerase is a member of the short-chain dehydrogenase/reductase superfamily, sharing sequence motifs and structural elements characteristic of this family of oxidoreductases and bacterial 4-epimerases. The protein was co-crystallized with coenzyme NADH and UDP-N-acetylmuramic acid, the latter an unintended inclusion and well known product of the bacterial enzyme MurB and a critical intermediate for bacterial cell wall synthesis. This is a non-native UDP sugar amongst archaea and was most likely incorporated from the Eschericha coli expression host during purification of the recombinant enzyme.
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    A genome-wide scan of positive selection signature using Ovine Infinium® HD SNP BeadChip in two Romney lines, selected for resistance or resilience to nematodes
    (2017-07-03) Yan J; Dukkipati VSR; Blair HT; Biggs PJ; Hamie JC; Greer A
    A study was undertaken to identify selection signatures associated with resistance to gastrointestinal nematodiasis in sheep. Ninety-three Romney sheep from two selection lines (resistant or resilient) were genotyped using the Ovine Infinium® HD SNP BeadChip, and extended haplotype homozygosity (EHH) and site-specific extended haplotype homozygosity (EHHS) analyses were undertaken. In total, 224 SNPs (147 in EHH and 77 in EHHS) were found to be significant (p <0.0001). Preliminary exploration of 10 SNPs found them to be located within two previously identified QTLs, namely LATRICH_2 and FECGEN, which were associated with nematode larval count and faecal egg count, respectively.