Mitochondrial Utilization of Competing Fuels Is Altered in Insulin Resistant Skeletal Muscle of Non-obese Rats (Goto-Kakizaki)

Aim: Insulin-resistant skeletal muscle is characterized by metabolic inflexibility with associated alterations in substrate selection, mediated by peroxisome-proliferator activated receptor δ (PPARδ). Although it is established that PPARδ contributes to the alteration of energy metabolism, it is not clear whether it plays a role in mitochondrial fuel competition. While nutrient overload may impair metabolic flexibility by fuel congestion within mitochondria, in absence of obesity defects at a mitochondrial level have not yet been excluded. We sought to determine whether reduced PPARδ content in insulin-resistant rat skeletal muscle of a non-obese rat model of T2DM (Goto-Kakizaki, GK) ameliorate the inhibitory effect of fatty acid (i.e., palmitoylcarnitine) on mitochondrial carbohydrate oxidization (i.e., pyruvate) in muscle fibers. Methods: Bioenergetic function was characterized in oxidative soleus (S) and glycolytic white gastrocnemius (WG) muscles with measurement of respiration rates in permeabilized fibers in the presence of complex I, II, IV, and fatty acid substrates. Mitochondrial content was measured by citrate synthase (CS) and succinate dehydrogenase activity (SDH). Western blot was used to determine protein expression of PPARδ, PDK isoform 2 and 4. Results: CS and SDH activity, key markers of mitochondrial content, were reduced by ∼10–30% in diabetic vs. control, and the effect was evident in both oxidative and glycolytic muscles. PPARδ (p < 0.01), PDK2 (p < 0.01), and PDK4 (p = 0.06) protein content was reduced in GK animals compared to Wistar rats (N = 6 per group). Ex vivo respiration rates in permeabilized muscle fibers determined in the presence of complex I, II, IV, and fatty acid substrates, suggested unaltered mitochondrial bioenergetic function in T2DM muscle. Respiration in the presence of pyruvate was higher compared to palmitoylcarnitine in both animal groups and fiber types. Moreover, respiration rates in the presence of both palmitoylcarnitine and pyruvate were reduced by 25 ± 6% (S), 37 ± 6% (WG) and 63 ± 6% (S), 57 ± 8% (WG) compared to pyruvate for both controls and GK, respectively. The inhibitory effect of palmitoylcarnitine on respiration was significantly greater in GK than controls (p < 10–3). Conclusion: With competing fuels, the presence of fatty acids diminishes mitochondria ability to utilize carbohydrate derived substrates in insulin-resistant muscle despite reduced PPARδ content

RESCALE: Review and Simulate Climate and Catchment Responses at Burrishoole

The climate of the Burrishoole catchment is projected to change significantly over the present century. Previous research of the catchment identified a scientific gap in knowledge in terms of understanding the implications of present and projected future changes in stream flow, water temperature, pH levels and DO concentrations on fish productivity in the catchment. To address this, a multidisciplinary team of scientists undertook an analysis of both present and likely future climate impacts on the catchment with a view to furthering the understanding of the inter-linkages between climate, climate change, and the freshwater ecosystem. The research findings outlined in the report provide climate change information at the catchment scale to assist catchment stakeholders in integrating climate change considerations into their decision-making processes. The report presents an in-depth assessment of the climate and environmental datasets from the catchment to establish if changes have occurred over the period of record. In order to assess the likely impacts of future changes in climate on the catchment, regional climate projections were developed and subsequently employed to simulate likely responses in stream flow and temperature, DOC and DO for the present century. The projected changes in both the climate and water-quality were then used to provide a basis for assessing impacts on fish growth and survival rates of salmonid and eel species in the catchment. The report provides a useful template for future studies, not just in the Burrishoole catchment but for other ecologically important catchments. The findings from the report are relevant to policy makers at the national scale; catchment managers at the regional scale; and, specifically, to stakeholders in the Burrishoole catchment, in developing adaptive responses to climate change.Funded under the Marine Research Sub-programme of the National Development Plan (2007-’13), as part of the Sea Change Strategy.Funder: Marine Institut

Technical Report: Review and Simulate Climate and Catchment Responses at Burrishoole (RESCALE)

Lead Partner: Department of Geography, National University of Ireland Maynooth Project Partners: School of Natural Sciences, Trinity College Dublin Marine Institute, Furnace, Newport, Co. MayoThis report demonstrates that the projected changes in the climate conditions of the Burrishoole catchment, if realised, will have wide ranging implications for all aspects of the catchment system, including water temperature and quality, stream flow hydrology, soil processes, and most notably the well-being of its aquatic environment. While the projected changes in climate and their implications, outlined in this report, are specific to the Burrishoole, they are illustrative of likely changes in similar characteristic catchments along the west coast of Ireland.Funder: Marine Institut

Changes in the variability and periodicity of precipitation in Scotland

This paper analyses the temporal and spatial changes in the amount and variability of rainfall in Scotland. The sequential Mann–Kendall test reveals that total annual precipitation has increased across Scotland since the 1970s with increasing trends in variability beginning between the mid-1960s and the mid-1970s. Whilst temporally consistent increasing trends in precipitation totals prevail in the West, many weather stations in the East have experienced subsequent trend turning points in the following two decades, explaining the larger magnitude of the trends in western Scotland in recent decades. Trend analyses on six measures of rainfall variability indicate an increase in rainfall variability during the period 1961–2000, as measured by the intra-annual variance, the winter to summer precipitation ratio and the annual cumulative sum range, with decreasing trends observed in the number of dry days. Periodicities associated with the North Atlantic Oscillation and the Atlantic Multidecadal Oscillation could explain the observed temporal variability of rainfall

Can bias correction and statistical downscaling methods improve the skill of seasonal precipitation forecasts?

Statistical downscaling methods are popular post-processing tools which are widely used in many sectors to adapt the coarse-resolution biased outputs from global climate simulations to the regional-to-local scale typically required by users. They range from simple and pragmatic Bias Correction (BC) methods, which directly adjust the model outputs of interest (e.g. precipitation) according to the available local observations, to more complex Perfect Prognosis (PP) ones, which indirectly derive local predictions (e.g. precipitation) from appropriate upper-air large-scale model variables (predictors). Statistical downscaling methods have been extensively used and critically assessed in climate change applications; however, their advantages and limitations in seasonal forecasting are not well understood yet. In particular, a key problem in this context is whether they serve to improve the forecast quality/skill of raw model outputs beyond the adjustment of their systematic biases. In this paper we analyze this issue by applying two state-of-the-art BC and two PP methods to downscale precipitation from a multimodel seasonal hindcast in a challenging tropical region, the Philippines. To properly assess the potential added value beyond the reduction of model biases, we consider two validation scores which are not sensitive to changes in the mean (correlation and reliability categories). Our results show that, whereas BC methods maintain or worsen the skill of the raw model forecasts, PP methods can yield significant skill improvement (worsening) in cases for which the large-scale predictor variables considered are better (worse) predicted by the model than precipitation. For instance, PP methods are found to increase (decrease) model reliability in nearly 40% of the stations considered in boreal summer (autumn). Therefore, the choice of a convenient downscaling approach (either BC or PP) depends on the region and the season.This study was partially supported by the SPECS and EUPORIAS projects, funded by the European Commission through the Seventh Framework Programme for Research under grant agreements 308378 and 308291, respectively. JMG acknowledges partial support from the project MULTI-SDM (CGL2015-66583-R, MINECO/FEDER)

A mixed methods process evaluation of a person-centred falls prevention program

Background RESPOND is a telephone-based falls prevention program for older people who present to a hospital emergency department (ED) with a fall. A randomised controlled trial (RCT) found RESPOND to be effective at reducing the rate of falls and fractures, compared with usual care, but not fall injuries or hospitalisations. This process evaluation aimed to determine whether RESPOND was implemented as planned, and identify implementation barriers and facilitators. Methods A mixed-methods evaluation was conducted alongside the RCT. Evaluation participants were the RESPOND intervention group (n=263) and the clinicians delivering RESPOND (n=7). Evaluation data were collected from participant recruitment and intervention records, hospital administrative records, audio-recordings of intervention sessions, and participant questionnaires. The Rochester Participatory Decision-Making scale (RPAD) was used to evaluate person-centredness (score range 0 (worst) - 9 (best)). Process factors were compared with pre-specified criteria to determine implementation fidelity. Six focus groups were held with participants (n=41), and interviews were conducted with RESPOND clinicians (n=6). Quantitative data were analysed descriptively and qualitative data thematically. Barriers and facilitators to implementation were mapped to the ‘Capability, Opportunity, Motivation – Behaviour’ (COM-B) behaviour change framework. Results RESPOND was implemented at a lower dose than the planned 10 hours over six months, with a median (IQR) of 2.9 hours (2.1, 4). The majority (76%) of participants received their first intervention session within one month of hospital discharge. Clinicians delivered the program in a person-centred manner with a median (IQR) RPAD score of 7 (6.5, 7.5) and 87% of questionnaire respondents were satisfied with the program. The reports from participants and clinicians suggested that implementation was facilitated by the use of positive and personally relevant health messages. Complex health and social issues were the main barriers to implementation. Conclusions RESPOND was person-centred and reduced falls and fractures at a substantially lower dose, using fewer resources, than anticipated. However, the low dose delivered may account for the lack of effect on falls injuries and hospitalisations. The results from this evaluation provide detailed information to guide future implementation of RESPOND of similar programs. Trial registration: This study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614000336684 (27 March 2014)

Exercise training decreases activation of the mitochondrial fission protein dynamin-related protein-1 in insulin-resistant human skeletal muscle

Defects in mitochondrial dynamics, the processes of fission, fusion, and mitochondrial autophagy, may contribute to metabolic disease including type 2 diabetes. Dynamin-related protein-1 (Drp1) is a GTPase protein that plays a central role in mitochondrial fission. We hypothesized that aerobic exercise training would decrease Drp1 Ser616 phosphorylation and increase fat oxidation and insulin sensitivity in obese (body mass index: 34.6 ± 0.8 kg/m2) insulin-resistant adults. Seventeen subjects performed supervised exercise for 60 min/day, 5 days/wk at 80–85% of maximal heart rate for 12 wk. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and fat oxidation was determined by indirect calorimetry. Skeletal muscle biopsies were obtained from the vastus lateralis muscle before and after the 12-wk program. The exercise intervention increased insulin sensitivity 2.1 ± 0.2-fold (P < 0.01) and fat oxidation 1.3 ± 0.3-fold (P < 0.01). Phosphorylation of Drp1 at Ser616 was decreased (pre vs. post: 0.81 ± 0.15 vs. 0.58 ± 0.14 arbitrary units; P < 0.05) following the intervention. Furthermore, reductions in Drp1 Ser616 phosphorylation were negatively correlated with increases in fat oxidation (r = −0.58; P < 0.05) and insulin sensitivity (rho = −0.52; P < 0.05). We also examined expression of genes related to mitochondrial dynamics. Dynamin1-like protein (DNM1L; P < 0.01), the gene that codes for Drp1, and Optic atrophy 1 (OPA1; P = 0.05) were significantly upregulated following the intervention, while there was a trend towards an increase in expression of both mitofusin protein MFN1 (P = 0.08) and MFN2 (P = 0.07). These are the first data to suggest that lifestyle-mediated improvements in substrate metabolism and insulin sensitivity in obese insulin-resistant adults may be regulated through decreased activation of the mitochondrial fission protein Drp1

Radon potential mapping of the Tralee-Castleisland and Cavan areas (Ireland) based on airborne gamma-ray spectrometry and geology

The probability of homes in Ireland having high indoor radon concentrations is estimated on the basis of known in-house radon measurements averaged over 10 km × 10 km grid squares. The scope for using airborne gamma-ray spectrometer data for the Tralee–Castleisland area of county Kerry and county Cavan to predict the radon potential (RP) in two distinct areas of Ireland is evaluated in this study. Airborne data are compared statistically with in-house radon measurements in conjunction with geological and ground permeability data to establish linear regression models and produce radon potential maps. The best agreement between the percentage of dwellings exceeding the reference level (RL) for radon concentrations in Ireland (% > RL), estimated from indoor radon data, and modelled RP in the Tralee–Castleisland area is produced using models based on airborne gamma-ray spectrometry equivalent uranium (eU) and ground permeability data. Good agreement was obtained between the % > RL from indoor radon data and RP estimated from eU data in the Cavan area using terrain specific models. In both areas, RP maps derived from eU data are spatially more detailed than the published 10 km grid map. The results show the potential for using airborne radiometric data for producing RP maps