Maternal creatine homeostasis is altered during gestation in the spiny mouse: is this a metabolic adaptation to pregnancy?

BACKGROUND: Pregnancy induces adaptations in maternal metabolism to meet the increased need for nutrients by the placenta and fetus. Creatine is an important intracellular metabolite obtained from the diet and also synthesised endogenously. Experimental evidence suggests that the fetus relies on a maternal supply of creatine for much of gestation. However, the impact of pregnancy on maternal creatine homeostasis is unclear. We hypothesise that alteration of maternal creatine homeostasis occurs during pregnancy to ensure adequate levels of this essential substrate are available for maternal tissues, the placenta and fetus. This study aimed to describe maternal creatine homeostasis from mid to late gestation in the precocial spiny mouse. METHODS: Plasma creatine concentration and urinary excretion were measured from mid to late gestation in pregnant (n = 8) and age-matched virgin female spiny mice (n = 6). At term, body composition and organ weights were assessed and tissue total creatine content determined. mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and the creatine transporter (CrT1) were assessed by RT-qPCR. Protein expression of AGAT and GAMT was also assessed by western blot analysis. RESULTS: Plasma creatine and renal creatine excretion decreased significantly from mid to late gestation (P < 0.001, P < 0.05, respectively). Pregnancy resulted in increased lean tissue (P < 0.01), kidney (P < 0.01), liver (P < 0.01) and heart (P < 0.05) mass at term. CrT1 expression was increased in the heart (P < 0.05) and skeletal muscle (P < 0.05) at term compared to non-pregnant tissues, and creatine content of the heart (P < 0.05) and kidney (P < 0.001) were also increased at this time. CrT1 mRNA expression was down-regulated in the liver (<0.01) and brain (<0.01) of pregnant spiny mice at term. Renal AGAT mRNA (P < 0.01) and protein (P < 0.05) expression were both significantly up-regulated at term, with decreased expression of AGAT mRNA (<0.01) and GAMT protein (<0.05) observed in the term pregnant heart. Brain AGAT (<0.01) and GAMT (<0.001) mRNA expression were also decreased at term. CONCLUSION: Change of maternal creatine status (increased creatine synthesis and reduced creatine excretion) may be a necessary adjustment of maternal physiology to pregnancy to meet the metabolic demands of maternal tissues, the placenta and developing fetus.

Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition

In this study, we investigated the efficacy of an LNA (locked nucleic acid)-modified DNA aptamer named RNV66 targeting VEGF against various breast cancer cell lines. Our results demonstrate that RNV66 efficiently inhibits breast cancer cell proliferation both in vitro and in vivo. Introduction of LNA nucleotides were crucial for higher efficacy. Furthermore, the binding interaction of RNV66 with VEGF was investigated using molecular dynamic simulations leading to the first computational model of the LNA aptamer-VEGF complex blocking its interaction with VEGF-receptor.

The lure of the local: community activism and place in Australia

The intertwined relationship between the built and natural environments characterises and defines coastal towns, especially those with significant heritage values. Our research is located in the context of the “sea change” phenomenon, which is fundamentally changing the coastal towns of Australia. Barbara Norman, a past national president of the Planning Institute of Australia (PIA), summarised the current struggle occurring in many of Australia’s coastal regions when she wrote: “the Australian coastline is littered with exhausted communities battling to save the character and environment of their townships” (Norman, 2008). The Australian National Sea Change Taskforce was established in 2004, as a response to these wider community and professional concerns, and seeks “to ensure that coastal development is managed with a focus on the sustainability of coastal communities and the coastal environment” (Gurran et al., 2006) concluded that more detailed research is needed to develop new responses to coastal development, particularly in terms of promoting community wellbeing, strengthening social cohesion, avoiding socio-economic and socio-spatial polarisation and preserving sense of place.

Costs and advance directives at the end of life: a case of the ‘Coaching Older Adults and Carers to have their preferences Heard (COACH)’ trial

BACKGROUND: Total costs associated with care for older people nearing the end of life and the cost variations related with end of life care decisions are not well documented in the literature. Healthcare utilisation and associated health care costs for a group of older Australians who entered Transition Care following an acute hospital admission were calculated. Costs were differentiated according to a number of health care decisions and outcomes including advance directives (ADs).

METHODS: Study participants were drawn from the Coaching Older Adults and Carers to have their preferences Heard (COACH) trial funded by the Australian National Health and Medical Research Council. Data collected included total health care costs, the type of (and when) ADs were completed and the place of death. Two-step endogenous treatment-regression models were employed to test the relationship between costs and a number of variables including completion of ADs.

RESULTS: The trial recruited 230 older adults with mean age 84 years. At the end of the trial, 53 had died and 80 had completed ADs. Total healthcare costs were higher for younger participants and those who had died. No statistically significant association was found between costs and completion of ADs.

CONCLUSION: For our frail study population, the completion of ADs did not have an effect on health care utilisation and costs. Further research is needed to substantiate these findings in larger and more diverse clinical cohorts of older people.

Dietary creatine supplementation during pregnancy: a study on the effects of creatine supplementation on creatine homeostasis and renal excretory function in spiny mice

Recent evidence obtained from a rodent model of birth asphyxia shows that supplementation of the maternal diet with creatine during pregnancy protects the neonate from multi-organ damage. However, the effect of increasing creatine intake on creatine homeostasis and biosynthesis in females, particularly during pregnancy, is unknown. This study assessed the impact of creatine supplementation on creatine homeostasis, body composition, capacity for de novo creatine synthesis and renal excretory function in non-pregnant and pregnant spiny mice. Mid-gestation pregnant and virgin spiny mice were fed normal chow or chow supplemented with 5 % w/w creatine for 18 days. Weight gain, urinary creatine and electrolyte excretion were assessed during supplementation. At post mortem, body composition was assessed by Dual-energy X-ray absorptiometry, or tissues were collected to assess creatine content and mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) and the creatine transporter (CrT1). Protein expression of AGAT and GAMT was also assessed by Western blot. Key findings of this study include no changes in body weight or composition with creatine supplementation; increased urinary creatine excretion in supplemented spiny mice, with increased sodium (P < 0.001) and chloride (P < 0.05) excretion in pregnant dams after 3 days of supplementation; lowered renal AGAT mRNA (P < 0.001) and protein (P < 0.001) expressions, and lowered CrT1 mRNA expression in the kidney (P < 0.01) and brain (P < 0.001). Creatine supplementation had minimal impact on creatine homeostasis in either non-pregnant or pregnant spiny mice. Increasing maternal dietary creatine consumption could be a useful treatment for birth asphyxia.

The work-based predictors of job engagement and job satisfaction experienced by community health professionals

Background: Job engagement represents a critical resource for community-based health care agencies to achieve high levels of effectiveness. However, studies examining the organisational sources of job engagement among health care professionals have generally overlooked those workers based in community settings.
Purpose: This study drew on the demand-control model, in addition to stressors that are more specific to community health services (e.g., unrewarding management practices), to identify conditions that are closely associated with the engagement experienced by a community health workforce. Job satisfaction was also included as a way of assessing how the predictors of job engagement differ from those associated with other job attitudes.
Methodology/Approach: Health and allied health care professionals (n = 516) from two
Australian community health services took part in the current investigation. Responses from the two organisations were pooled and analysed using linear multiple regression.
Findings: The analyses revealed that three working conditions were predictive of both job engagement and job satisfaction (i.e., job control, quantitative demands and unrewarding management practices). There was some evidence of differential effects with cognitive demands being associated with job engagement, but not job satisfaction.
Practice Implications: The results provide important insights into the working conditions that, if addressed, could play key roles in building a more engaged and satisfied community health workforce. Further, working conditions like job control and management practices are amenable to change and thus represent important areas where community health services could enhance the energetic and motivational resources of their employees.

Losses and recovery of organic carbon from a seagrass ecosystem following disturbance

Seagrasses are among the Earth's most efficient and long-term carbon sinks, but coastal development threatens this capacity. We report new evidence that disturbance to seagrass ecosystems causes release of ancient carbon. In a seagrass ecosystem that had been disturbed 50 years ago, we found that soil carbon stocks declined by 72%, which, according to radiocarbon dating, had taken hundreds to thousands of years to accumulate. Disturbed soils harboured different benthic bacterial communities (according to 16S rRNA sequence analysis), with higher proportions of aerobic heterotrophs compared with undisturbed. Fingerprinting of the carbon (via stable isotopes) suggested that the contribution of autochthonous carbon (carbon produced through plant primary production) to the soil carbon pool was less in disturbed areas compared with seagrass and recovered areas. Seagrass areas that had recovered from disturbance had slightly lower (35%) carbon levels than undisturbed, but more than twice as much as the disturbed areas, which is encouraging for restoration efforts. Slow rates of seagrass recovery imply the need to transplant seagrass, rather than waiting for recovery via natural processes. This study empirically demonstrates that disturbance to seagrass ecosystems can cause release of ancient carbon, with potentially major global warming consequences.

Comparison of marine macrophytes for their contributions to blue carbon sequestration

Many marine ecosystems have the capacity for long-term storage of organic carbon (C) in what are termed "blue carbon" systems. While blue carbon systems (saltmarsh, mangrove, and seagrass) are efficient at long-term sequestration of organic carbon (C), much of their sequestered C may originate from other (allochthonous) habitats. Macroalgae, due to their high rates of production, fragmentation, and ability to be transported, would also appear to be able to make a significant contribution as C donors to blue C habitats. In order to assess the stability of macroalgal tissues and their likely contribution to long-term pools of C, we applied thermogravimetric analysis (TGA) to 14 taxa of marine macroalgae and coastal vascular plants. We assessed the structural complexity of multiple lineages of plant and tissue types with differing cell wall structures and found that decomposition dynamics varied significantly according to differences in cell wall structure and composition among taxonomic groups and tissue function (photosynthetic vs. attachment). Vascular plant tissues generally exhibited greater stability with a greater proportion of mass loss at temperatures > 300 degrees C (peak mass loss -320 degrees C) than macroalgae (peak mass loss between 175-300 degrees C), consistent with the lignocellulose matrix of vascular plants. Greater variation in thermogravimetric signatures within and among macroalgal taxa, relative to vascular plants, was also consistent with the diversity of cell wall structure and composition among groups. Significant degradation above 600 degrees C for some macroalgae, as well as some belowground seagrass tissues, is likely due to the presence of taxon-specific compounds. The results of this study highlight the importance of the lignocellulose matrix to the stability of vascular plant sources and the potentially significant role of refractory, taxon-specific compounds (carbonates, long-chain lipids, alginates, xylans, and sulfated polysaccharides) from macroalgae and seagrasses for their long-term sedimentary C storage. This study shows that marine macroalgae do contain refractory compounds and thus may be more valuable to long-term carbon sequestration than we previously have considered.

Do the foods advertised in Australian supermarket catalogues reflect national dietary guidelines?

Unhealthy diets are the major contributor to poor health in Australia and many countries globally. The majority of food spending in Australia occurs in supermarkets, which stock and sell both healthy and unhealthy foods. This study aimed to compare the foods advertised in the marketing catalogues (circulars) from four Australian supermarket chains with the Australian Guide to Healthy Eating. The content of national online weekly supermarket catalogues from four major Australian supermarket retailers was audited from June-September 2013 (12 weeks). Advertised products were categorized as (i) foods in the five core food groups (plus water); (ii) discretionary foods plus fats and oils; (iii) alcohol and (iv) other (food not fitting into any other category). Across all chains combined, 34.2% of foods advertised were from the five core food groups, 43.3% were discretionary foods, 8.5% were alcohol and the remaining 14.0% were 'other' foods. The percentage of advertised foods in the five core food groups varied between 29.3 and 38.3% across the four chains, whereas the percentage of discretionary foods varied between 34.8 and 49.0%. Australian supermarket catalogues heavily promote discretionary foods and contribute towards an environment that supports unhealthy eating behaviour. Strategies to increase the ratio of healthy-to-unhealthy foods need to be explored as part of efforts to improve population diets.

Clinical MRSA isolates from skin and soft tissue infections show increased in vitro production of phenol soluble modulins

BACKGROUND: Phenol-soluble modulins (PSMs) are amphipathic, pro-inflammatory proteins secreted by most Staphylococcus aureus isolates. This study tested the hypothesis that in vitro PSM production levels are associated with specific clinical phenotypes. METHODS: 177 methicillin-resistant S. aureus (MRSA) isolates from infective endocarditis (IE), skin and soft tissue infection (SSTI), and hospital-acquired/ventilator-associated pneumonia (HAP) were matched by geographic origin, then genotyped using spa-typing. In vitro PSM production was measured by high performance liquid chromatography/mass spectrometry. Statistical analysis was performed using Chi-squared or Kruskal-Wallis tests as appropriate. RESULTS: Spa type 1 was significantly more common in SSTI isolates (62.7% SSTI; 1.7% IE; 16.9% HAP; p < 0.0001) while HAP and IE isolates were more commonly spa type 2 (0% SSTI; 37.3% IE; 40.7% HAP; p < 0.0001). USA300 isolates produced the highest levels of PSMs in vitro. SSTI isolates produced significantly higher quantities of PSMα1-4, PSMβ1, and δ-toxin than other isolates (p < 0.001). These findings persisted when USA300 isolates were excluded from analysis. CONCLUSIONS: Increased in vitro production of PSMs is associated with an SSTI clinical source. This significant association persisted after exclusion of USA300 genotype isolates from analysis, suggesting that PSMs play a particularly important role in the pathogenesis of SSTI as compared to other infection types.

Maternal creatine supplementation during pregnancy prevents long-term changes in diaphragm muscle structure and function after birth asphyxia

Using a model of birth asphyxia, we previously reported significant structural and functional deficits in the diaphragm muscle in spiny mice, deficits that are prevented by supplementing the maternal diet with 5% creatine from mid-pregnancy. The long-term effects of this exposure are unknown. Pregnant spiny mice were fed control or 5% creatine-supplemented diet for the second half of pregnancy, and fetuses were delivered by caesarean section with or without 7.5 min of in-utero asphyxia. Surviving pups were raised by a cross-foster dam until 33±2 days of age when they were euthanized to obtain the diaphragm muscle for ex-vivo study of twitch tension and muscle fatigue, and for structural and enzymatic analyses. Functional analysis of the diaphragm revealed no differences in single twitch contractile parameters between any groups. However, muscle fatigue, induced by stimulation of diaphragm strips with a train of pulses (330 ms train/sec, 40 Hz) for 300 sec, was significantly greater for asphyxia pups compared with controls (p<0.05), and this did not occur in diaphragms of creatine + asphyxia pups. Birth asphyxia resulted in a significant increase in the proportion of glycolytic, fast-twitch fibres and a reduction in oxidative capacity of Type I and IIb fibres in male offspring, as well as reduced cross-sectional area of all muscle fibre types (Type I, IIa, IIb/d) in both males and females at 33 days of age. None of these changes were observed in creatine + asphyxia animals. Thus, the changes in diaphragm fatigue and structure induced by birth asphyxia persist long-term but are prevented by maternal creatine supplementation.

Metabolites derived from the tropical seagrass Thalassia testudinum are bioactive against pathogenic Labyrinthula sp

Temperate and tropical seagrasses are susceptible to wasting disease outbreaks caused by pathogenic protists of the genus Labyrinthula. Even though there is an increasing awareness of the environmental conditions that influence the etiology of seagrass-. Labyrinthula disease dynamics, the biochemical basis of seagrass defense responses, in particular chemical defenses, is still vastly understudied. Using an in vitro bioassay, we provide evidence that previously characterized phenolic and potentially novel, undescribed non-phenolic metabolites derived from Thalassia testudinum Banks ex Konig exhibit anti-labyrinthulid activity. All phenolic compounds tested displayed dose-dependent behavior and selected combinations interacted synergistically. The flavone glycoside thalassiolin B was roughly 20-100 times more active than any phenolic acid tested. Based upon values reported in the literature, it was calculated that infected specimens of T. testudinum contain natural concentrations of phenolic acids that are consistently greater than what is required to inhibit Labyrinthula growth. This suggests that while there may be an ample supply of phenolic-based derivatives available to inhibit Labyrinthula growth, they may not be readily bio-accessible.Using a bioactivity-guided approach, a semi-purified chemical fraction from T. testudinum was found to contain anti-labyrinthulid activity. 1H NMR spectra for this fraction lacked aromatic hydrogen signals, suggesting that the bioactive compound was non-aromatic in nature. Furthermore, the LC-MS fragmentation patterns were suggestive of the presence of glycosylated natural products of an unknown structural class. This has the potential to provide a foundation for future chemical investigations.

Transformations of teaching and learning through digital technologies

This chapter is a critical synthesis of research related to the transformations that take place when digital technologies are incorporated into teaching and learning practices. In developing this synthesis, research from all levels of education was reviewed with a focus on the opportunities digital technologies offer for cognitive, pedagogical, affective and professional change. The chapter is structured in alignment with Pierce and Stacey’s (Pierce and Stacey, Int J Comput Math Learn 15(1):1–20 2010) map of pedagogical opportunities in which three dimensions for educational transformation were identified: tasks, classroom, and subject. A discussion of future directions for research into technology enhanced mathematics education concludes the review.

Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring

Background: Animal studies report a nephron deficit in offspring exposed to maternal diabetes, yet are limited to models of severe hyperglycaemia which do not reflect the typical clinical condition and which are associated with foetal growth restriction that may confound nephron endowment. We aimed to assess renal morphology and function in offspring of leptin receptor deficient mice (Leprdb/+) and hypothesized that exposure to impaired maternal glucose tolerance (IGT) would be detrimental to the developing kidney.

Methods: Nephron endowment was assessed in offspring of C57BKS/J Leprdb/+ and +/+ mice at embryonic day (E)18 and postnatal day (PN)21 using design-based stereology. Transcutaneous measurement of renal function and total glomerular volume were assessed in 6-month-old offspring. Only +/+ offspring of Leprdb/+ dams were analysed.

Results: Compared with +/+ dams, Leprdb/+ dams had a 20% and 35% decrease in glucose tolerance prior to pregnancy and at E17.5 respectively. Offspring of IGT Leprdb/+ dams had approximately 15% fewer nephrons at E18.5 and PN21 than offspring of +/+ dams. There was no difference in offspring bodyweight. Despite normal renal function, total glomerular volume was 13% greater in 6-month-old offspring of IGT Leprdb/+ dams than in +/+ offspring.

Conclusions: IGT throughout gestation resulted in a nephron deficit that was established early in renal development. Maternal IGT was associated with glomerular hypertrophy in adult offspring, likely a compensatory response to maintain normal renal function. Given the increasing prevalence of IGT, monitoring glucose from early in gestation may be important to prevent altered kidney morphology.

Identifying knowledge gaps in seagrass research and management: An Australian perspective.

Seagrass species form important marine and estuarine habitats providing valuable ecosystem services and functions. Coastal zones that are increasingly impacted by anthropogenic development have experienced substantial declines in seagrass abundance around the world. Australia, which has some of the world's largest seagrass meadows and is home to over half of the known species, is not immune to these losses. In 1999 a review of seagrass ecosystems knowledge was conducted in Australia and strategic research priorities were developed to provide research direction for future studies and management. Subsequent rapid evolution of seagrass research and scientific methods has led to more than 70% of peer reviewed seagrass literature being produced since that time. A workshop was held as part of the Australian Marine Sciences Association conference in July 2015 in Geelong, Victoria, to update and redefine strategic priorities in seagrass research. Participants identified 40 research questions from 10 research fields (taxonomy and systematics, physiology, population biology, sediment biogeochemistry and microbiology, ecosystem function, faunal habitats, threats, rehabilitation and restoration, mapping and monitoring, management tools) as priorities for future research on Australian seagrasses. Progress in research will rely on advances in areas such as remote sensing, genomic tools, microsensors, computer modeling, and statistical analyses. A more interdisciplinary approach will be needed to facilitate greater understanding of the complex interactions among seagrasses and their environment.