Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors

Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; IP) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol. © 2013 den Hartog et al

Accommodating Dynamic Oceanographic Processes and Pelagic Biodiversity in Marine Conservation Planning

Pelagic ecosystems support a significant and vital component of the ocean's productivity and biodiversity. They are also heavily exploited and, as a result, are the focus of numerous spatial planning initiatives. Over the past decade, there has been increasing enthusiasm for protected areas as a tool for pelagic conservation, however, few have been implemented. Here we demonstrate an approach to plan protected areas that address the physical and biological dynamics typical of the pelagic realm. Specifically, we provide an example of an approach to planning protected areas that integrates pelagic and benthic conservation in the southern Benguela and Agulhas Bank ecosystems off South Africa. Our aim was to represent species of importance to fisheries and species of conservation concern within protected areas. In addition to representation, we ensured that protected areas were designed to consider pelagic dynamics, characterized from time-series data on key oceanographic processes, together with data on the abundance of small pelagic fishes. We found that, to have the highest likelihood of reaching conservation targets, protected area selection should be based on time-specific data rather than data averaged across time. More generally, we argue that innovative methods are needed to conserve ephemeral and dynamic pelagic biodiversity

Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition

BACKGROUND: Over the past several years our research group has taken a systematic, comprehensive approach to determining the effects on body function (hormonal and non-hormonal) of varying the amounts and types of proteins, carbohydrates and fats in the diet. We have been particularly interested in the dietary management of type 2 diabetes. Our objective has been to develop a diet for people with type 2 diabetes that does not require weight loss, oral agents, or insulin, but that still controls the blood glucose concentration. Our overall goal is to enable the person with type 2 diabetes to control their blood glucose by adjustment in the composition rather than the amount of food in their diet. METHODS: This paper is a brief summary and review of our recent diet-related research, and the rationale used in the development of diets that potentially are useful in the treatment of diabetes. RESULTS: We determined that, of the carbohydrates present in the diet, absorbed glucose is largely responsible for the food-induced increase in blood glucose concentration. We also determined that dietary protein increases insulin secretion and lowers blood glucose. Fat does not significantly affect blood glucose, but can affect insulin secretion and modify the absorption of carbohydrates. Based on these data, we tested the efficacy of diets with various protein:carbohydrate:fat ratios for 5 weeks on blood glucose control in people with untreated type 2 diabetes. The results were compared to those obtained in the same subjects after 5 weeks on a control diet with a protein:carbohydrate:fat ratio of 15:55:30. A 30:40:30 ratio diet resulted in a moderate but significant decrease in 24-hour integrated glucose area and % total glycohemoglobin (%tGHb). A 30:20:50 ratio diet resulted in a 38% decrease in 24-hour glucose area, a reduction in fasting glucose to near normal and a decrease in %tGHb from 9.8% to 7.6%. The response to a 30:30:40 ratio diet was similar. CONCLUSION: Altering the diet composition could be a patient-empowering method of improving the hyperglycemia of type 2 diabetes without weight loss or pharmacologic intervention

Training tomorrow's doctors in diabetes: self-reported confidence levels, practice and perceived training needs of post-graduate trainee doctors in the UK. A multi-centre survey

<p>Abstract</p> <p>Objective</p> <p>To assess the confidence, practices and perceived training needs in diabetes care of post-graduate trainee doctors in the UK.</p> <p>Methods</p> <p>An anonymised postal questionnaire using a validated 'Confidence Rating' (CR) scale was applied to aspects of diabetes care and administered to junior doctors from three UK hospitals. The frequency of aspects of day-to-day practice was assessed using a five-point scale with narrative description in combination with numeric values. Respondents had a choice of 'always' (100%), 'almost always' (80–99%), 'often' (50–79%), 'not very often' (20–49%) and 'rarely' (less than 20%). Yes/No questions were used to assess perception of further training requirements. Additional 'free-text' comments were also sought.</p> <p>Results</p> <p>82 doctors completed the survey. The mean number of years since medical qualification was 3 years and 4 months, (range: 4 months to 14 years and 1 month). Only 11 of the respondents had undergone specific diabetes training since qualification.</p> <p>4(5%) reported 'not confident' (CR1), 30 (37%) 'satisfactory but lacked confidence' (CR2), 25 (30%) felt 'confident in some cases' (CR3) and 23 (28%) doctors felt fully confident (CR4) in diagnosing diabetes. 12 (15%) doctors would always, 24 (29%) almost always, 20 (24%) often, 22 (27%) not very often and 4 (5%) rarely take the initiative to optimise gcaemic control. 5 (6%) reported training in diagnosis of diabetes was adequate while 59 (72%) would welcome more training. Reported confidence was better in managing diabetes emergencies, with 4 (5%) not confident in managing hypoglycaemia, 10 (12%) lacking confidence, 22 (27%) confident in some cases and 45 (55%) fully confident in almost all cases. Managing diabetic ketoacidosis, 5 (6%) doctors did not feel confident, 16 (20%) lacked confidence, 20 (24%) confident in some cases, and 40 (50%) felt fully confident in almost all cases.</p> <p>Conclusion</p> <p>There is a lack of confidence in managing aspects of diabetes care, including the management of diabetes emergencies, amongst postgraduate trainee doctors with a perceived need for more training. This may have considerable significance and further research is required to identify the causes of deficiencies identified in this study.</p

Review of the projected impacts of climate change on coastal fishes in southern Africa

The coastal zone represents one of the most economically and ecologically important ecosystems on the planet, none more so than in southern Africa. This manuscript examines the potential impacts of climate change on the coastal fishes in southern Africa and provides some of the first information for the Southern Hemisphere, outside of Australasia. It begins by describing the coastal zone in terms of its physical characteristics, climate, fish biodiversity and fisheries. The region is divided into seven biogeographical zones based on previous descriptions and interpretations by the authors. A global review of the impacts of climate change on coastal zones is then applied to make qualitative predictions on the likely impacts of climate change on migratory, resident, estuarine-dependent and catadromous fishes in each of these biogeographical zones. In many respects the southern African region represents a microcosm of climate change variability and of coastal habitats. Based on the broad range of climate change impacts and life history styles of coastal fishes, the predicted impacts on fishes will be diverse. If anything, this review reveals our lack of fundamental knowledge in this field, in particular in southern Africa. Several research priorities, including the need for process-based fundamental research programs are highlighted

Automated postural responses are modified in a functional manner by instruction.

Contains fulltext : 70025.pdf (publisher's version ) (Open Access)The restoration of upright balance after a perturbation relies on highly automated and, to a large extent, stereotyped postural responses. Although these responses occur before voluntary control comes into play, previous research has shown that they can be functionally modulated on the basis of cognitive set (experience, advanced warning, instruction, etc.). It is still unknown, however, how the central nervous system deals with situations in which the postural response is not necessarily helpful in the execution of a task. In the present study, the effects of instruction on automated postural responses in neck, trunk, shoulder, and leg muscles were investigated when people were either instructed to recover balance after being released from an inclined standing posture [balance recovery (BR) trials], or not to recover at all and fall onto a safety mattress in the most comfortable way [fall (F) trials], in both backward and leftward directions. Participants were highly successful in following the instructions, consistently exhibiting stepping responses for balance recovery in BR trials, and suppressing stepping in the F trials. Yet EMG recordings revealed similar postural responses with onset latencies between 70 and 130 ms in both BR and F trials, with slightly delayed responses in F trials. In contrast, very pronounced and early differences were observed between BR and F trials in response amplitudes, which were generally much higher in BR than in F trials, but with clear differentiation between muscles and perturbation directions. These results indicate that a balance perturbation always elicits a postural response, irrespective of the task demands. However, when a specific balance recovery response is not desired after a perturbation, postural responses can be selectively downregulated and integrated into the motor output in a functional and goal-oriented way