Rachel Page

Acetyl-CoA carboxylase exerts strong flux control over lipid synthesis in plants

The importance of acetyl-CoA carboxylase in regulation of lipid synthesis for barley and maize leaves has been quantitatively assessed using, as specific inhibitors, the herbicides fluazifop and sethoxydim. Apparent flux control coefficients of about 0.58 and 0.52 were determined for acetyl-CoA carboxylase in barley and maize leaves, respectively. These results show that acetyl-CoA carboxylase is the major flux controlling enzyme for light-stimulated lipid synthesis in these tissues.

Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity

Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silencing by miRNAs are potential environmental modulators of skeletal muscle plasticity to chronic exercise in healthy and diseased populations. We utilized transcriptome networks to connect exercise-induced differential methylation and miRNA with functional skeletal muscle plasticity. Biopsies of the vastus lateralis were collected from middle-aged Polynesian men and women with morbid obesity (44 kg/m(2) ± 10) and Type 2 diabetes before and following 16 wk of resistance (n = 9) or endurance training (n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses were obtained via microarray, filtered by novel effect-size based false discovery rate probe selection preceding bioinformatic interrogation. Metabolic and microvascular transcriptome topology dominated the network landscape following endurance exercise. Lipid and glucose metabolism modules were connected to: microRNA (miR)-29a; promoter region hypomethylation of nuclear receptor factor (NRF1) and fatty acid transporter (SLC27A4), and hypermethylation of fatty acid synthase, and to exon hypomethylation of 6-phosphofructo-2-kinase and Ser/Thr protein kinase. Directional change in the endurance networks was validated by lower intramyocellular lipid, increased capillarity, GLUT4, hexokinase, and mitochondrial enzyme activity and proteome. Resistance training also lowered lipid and increased enzyme activity and caused GLUT4 promoter hypomethylation; however, training was inconsequential to GLUT4, capillarity, and metabolic transcriptome. miR-195 connected to negative regulation of vascular development. To conclude, integrated molecular network modelling revealed differential DNA methylation and miRNA expression changes occur in skeletal muscle in response to chronic exercise training that are most pronounced with endurance training and topographically associated with functional metabolic and microvascular plasticity relevant to diabetes rehabilitation.

The assessment of viability in isolated rat hepatocytes

Isolated rat hepatocytes are used in many metabolic studies, but the viability of these cell preparations is often not adequately established. The present study shows that ATP content is a more reliable index of metabolic viability than trypan blue exclusion. At some of the low trypan blue exclusion levels quoted in the literature, a high percentage of cell preparations is likely to be nonviable by the criterion of ATP content. We suggest that ATP content measured on initial cell preparations and at the end of all incubation procedures is essential for establishing cell viability for metabolic studies on isolated hepatocytes.

Degradation of [Dha7]MC-LR by a Microcystin Degrading Bacterium Isolated from Lake Rotoiti, New Zealand

For the first time a microcystin-degrading bacterium (NV-3 isolate) has been isolated and characterized from a NZ lake. Cyanobacterial blooms in New Zealand (NZ) waters contain microcystin (MC) hepatotoxins at concentrations which are a risk to animal and human health. Degradation of MCs by naturally occurring bacteria is an attractive bioremediation option for removing MCs from drinking and recreational water sources. The NV-3 isolate was identified by 16S rRNA sequence analysis and found to have 100% nucleotide sequence homology with the Sphingomonas MC-degrading bacterial strain MD-1 from Japan. The NV-3 isolate (concentration of 1.0 × 108 CFU/mL) at 30°C degraded a mixture of [Dha7]MC-LR and MC-LR (concentration 25 μg/mL) at a maximum rate of 8.33 μg/mL/day. The intermediate by-products of [Dha7]MC-LR degradation were detected and similar to MC-LR degradation by-products. The presence of three genes (mlrA, mlrB, and mlrC), that encode three enzymes involved in the degradation of MC-LR, were identified in the NV-3 isolate. This study confirmed that degradation of [Dha7]MC-LR by the Sphingomonas isolate NV-3 occurred by a similar mechanism previously described for MC-LR by Sphingomonas strain MJ-PV (ACM-3962). This has important implications for potential bioremediation of toxic blooms containing a variety of MCs in NZ waters.

Exercise intervention in New Zealand Polynesian peoples with type 2 diabetes: Cultural considerations and clinical trial recommendations.

The Maori and Pacific Islands peoples of New Zealand suffer a greater burden of type 2 diabetes mellitus (T2DM) and associated comorbidities than their European counterparts. Empirical evidence supports the clinical application of aerobic and resistance training for effective diabetes management and potential remission, but few studies have investigated the effectiveness of these interventions in specific ethnic cohorts. We recently conducted the first trial to investigate the effect of prescribed exercise training in Polynesian people with T2DM. This article presents the cultural considerations undertaken to successfully implement the study. The research procedures were accepted and approved by cultural liaisons and potential participants. The approved methodology involved a trial evaluating and comparing the effects of two, 16-week exercise regimens (i.e. aerobic training and resistance training) on glycosylated haemoglobin (HbA1c), related diabetes markers (i.e. insulin resistance, blood lipids, relevant cytokines and anthropometric and hemodynamic indices) and health-related quality of life. Future exercise-related research or implementation strategies in this cohort should focus on cultural awareness and techniques to enhance participation and compliance. Our approach to cultural consultation could be considered by researchers undertaking trials in this and other ethnic populations suffering an extreme burden of T2DM, including indigenous Australians and Americans.

Exercise training in high-risk ethnic populations with type 2 diabetes: a systematic review of clinical trials.

BACKGROUND To review clinical trials that have prescribed exercise training in high-risk, ethnic populations with type 2 diabetes mellitus (T2DM) and delineate areas for future research. METHOD A systematic review using computerized databases was performed. RESULTS The systematic review located nine trials, including four uncontrolled trials, and five randomized controlled trials (RCTs) that included 521 participants. Cohorts studied included African, Indian, Polynesian, Hispanic, Arabian, and Chinese peoples and interventions included aerobic training, resistance training or a combination thereof. Several trials documented improvements in HbA1c, insulin action, body composition, blood lipids and systolic and diastolic blood pressure. In general, a longer duration and greater frequency of training resulted in greater adaptation. Studies demonstrating no effect were generally limited by an inadequate intervention. There was evidence of differential training responses between Caucasians and non-Caucasians in two studies drawing such comparisons. CONCLUSIONS Robust RCTs prescribing appropriate, targeted interventions and investigating relevant outcomes may be required to stimulate greater advocacy for exercise as a therapeutic adjunct for diabetes management in these populations. Investigations should be extended to other high-risk populations, particularly indigenous peoples who suffer an extreme burden of T2DM. Translation of research into clinical application should remain the overall objective.

The Importance of Global Citizenship to Higher Education: The Role of Short-Term Study Abroad

An increasing number of institutions actively promote internationalisation as a key strategy, implying that the development of a “global citizenry” is an integral part of their educational mission. To fulfil this strategy, four constructs must be addressed: (1) what is global citizenship?, (2) why is global citizenship important? (3) how do we measure global citizenship?, and (4) how do we foster global citizenship? (1) Although global citizenship is a highly contested and multifaceted term, three key dimensions are commonly accepted: social responsibility, global awareness, and civic engagement. (2) Today’s graduates are critically dependent on an interconnected world, and universities have a responsibility to promote global mindedness, to provide greater employment opportunities for their graduates, and to respond to political calls for enhanced national security. (3) There is a consensus that the natural and built environment is the context in which global citizenship

Regulation of the delta and alpha epithelial sodium channel (ENaC) by ubiquitination and Nedd8.

The δ epithelial sodium channel (δENaC) is a proton‐activated, sodium‐selective, amiloride‐sensitive ion channel in the ENaC/degenerin family of ion channels involved in blood pressure regulation and mechanosensation. Other ENaC family members are subject to ubiquitin modification leading to internalization from the cell surface, and degradation of the channel. Here, we show that δENaC is also modified by ubiquitin on three intracellular lysine residues. Absence of these lysines abolished ubiquitin modification of δENaC and increased cell surface levels of δENaC. Although the HECT‐domain ubiquitin ligase Nedd4‐2 reduced amiloride‐sensitive current generated by δβγENaC‐containing channels, δENaC does not contain a binding site for Nedd4‐2; therefore, this effect is probably mediated by the βγENaC subunits. Nedd8, a ubiquitin‐like protein that regulates RING‐domain E3 ubiquitin ligases, promoted δENaC ubiquitination, decreased both the intracellular and cell surface δENaC populations, and decreased δβγENaC amiloride‐sensitive short circuit current (Isc‐amiloride) in a mammalian epithelium. Nedd8 also promoted α− and γENaC ubiquitination, decreased the cell surface pools, and decreased αβγENaC Isc‐amiloride. Conversely, XIAP, a single subunit RING E3 ligase, decreased ubiquitinated δENaC, increased the δENaC cell surface pool and increased δβγENaC Isc‐amiloride. Therefore δ− and α − βγENaC channel function may be influenced by RING‐domain E3 ubiquitin ligases. J. Cell. Physiol. 228: 2190–2201, 2013.

Reliability tests and guidelines for B‐mode ultrasound assessment of central adiposity

Ultrasound represents a validated and relatively inexpensive diagnostic device for assessing central adiposity; however, widespread adoption has been impeded by the lack of reliable standard operating procedures.

Regulation of Rates of Ethanol Metabolism and Liver [NAD+]/[NADH] Ratio

Factors that control the rate of alcohol metabolism in mammals have been the subject of debate for many years (for detailed reviews, see Crow, 1985; Crow and Hardman, 1989). There have been two main theories as to the major rate limitation on the ethanol metabolic pathway. The first theory was that the rate at which NADH (generated in the alcohol and aldehyde dehydrogenase reactions) could be reoxidised to NAD+ was limiting (Hawkins and Kalant, 1972; Khanna and Israel, 1980; Thurman et al, 1989). This theory arose from the observation that the ratio of free [NAD+]/[NADH] in liver cytosol decreased during ethanol metabolism. It was assumed either that the liver ran out of NAD+, because the rate of reoxidation of NADH was limiting, and this lack of NAD+ then limited the rate of the alcohol dehydrogenase (ADH) reaction (Khanna and Israel, 1980) or that NADH accumulated and caused product inhibition of ADH (Thurman et al, 1989). The second theory was that the amount of ADH present in the liver was the main rate-determining factor for the pathway (Crow et al, 1977; Cornell et al, 1979; Braggins and Crow, 1981; Cornell, 1983; Bosron et al, 1983). This theory arose in part from observations that the activity of liver ADH measured in vitro was only slightly more than necessary to explain rates of ethanol metabolism observed in vivo (Crow et al, 1977; Cornell et al, 1979; Braggins and Crow, 1981). ADH was not present ‘in excess’ as had sometimes been claimed (Hawkins and Kalant, 1972; Kalant et al, 1975). It was also observed that variations in ADH activity induced by castration (Rachamin et al, 1980; Mezey et al, 1980; Cicero et al, 1980, 1982), starvation (Braggins and Crow, 1981; Lumeng et al, 1979, 1980) or stress (Mezey et al, 1979) were associated with corresponding changes in rates of ethanol metabolism.