The Relative Attenuation of Self-stimulation, Eating and Drinking Produced by Dopamine-Receptor Blockade

Spiroperidol, which blocks dopamine (DA) receptors, attenuated self-stimulation of the nucleus accumbens, septal area, hippocampus, anterior hypothalamus and ventral tegmental area. Dopamine is thus involved in self-stimulation of many sites (in addition to the lateral hypothalamus). The attenuation was not a simple motor impairment of the speed of bar-pressing in that the nucleus accumbens and septal self-stimulation rates were lower than those in treated animals self-stimulating at other sites (Experiment 1). Feeding was partly attenuated, and drinking was much less attenuated by the spiroperidol. Since the rats bar-pressed for brain- stimulation reward, chewed pellets to eat, and licked a tube to drink, dopamine-receptor blockade may attenuate complex motor responses most. Alternatively, the blockade could affect brain- stimulation reward more than the controls of eating, and these latter more than the controls of drinking (Experiment 2). In Experiment 3, feeding and drinking were equally and severely attenuated when rats had to bar-press to obtain food or water. The attenuation was to a level similar to that found for self-stimulation. These experiments suggest that dopamine receptor blockade impairs eating, drinking and self-stimulation by interfering with complex motor responses

Biotic homogenisation and differentiation as directional change in beta diversity: synthesising driver–response relationships to develop conceptualmodels across ecosystems

Biotic homogenisation is defined as decreasing dissimilarity among ecological assemblages sampled within a given spatial area over time. Biotic differentiation, in turn, is defined as increasing dissimilarity over time. Overall, changes in the spatial dissimilarities among assemblages (termed ‘beta diversity’) is an increasingly recognised feature of broader biodiversity change in the Anthropocene. Empirical evidence of biotic homogenisation and biotic differentiation remains scattered across different ecosystems. Most meta-analyses quantify the prevalence and direction of change in beta diversity, rather than attempting to identify underlying ecological drivers of such changes. By conceptualising the mechanisms that contribute to decreasing or increasing dissimilarity in the composition of ecological assemblages across space, environmental managers and conservation practitioners can make informed decisions about what interventions may be required to sustain biodiversity and can predict potential biodiversity outcomes of future disturbances. We systematically reviewed and synthesised published empirical evidence for ecological drivers of biotic homogenisation and differentiation across terrestrial, marine, and freshwater realms to derive conceptual models that explain changes in spatial beta diversity. We pursued five key themes in our review: (i) temporal environmental change; (ii) disturbance regime; (iii) connectivity alteration and species redistribution; (iv) habitat change; and (v) biotic and trophic interactions. Our first conceptual model highlights how biotic homogenisation and differentiation can occur as a function of changes in local (alpha) diversity or regional (gamma) diversity, independently of species invasions and losses due to changes in species occurrence among assemblages. Second, the direction and magnitude of change in beta diversity depends on the interaction between spatial variation (patchiness) and temporal variation (synchronicity) of disturbance events. Third, in the context of connectivity and species redistribution, divergent beta diversity outcomes occur as different species have different dispersal characteristics, and the magnitude of beta diversity change associated with species invasions also depends strongly on alpha and gamma diversity prior to species invasion. Fourth, beta diversity is positively linked with spatial environmental variability, such that biotic homogenisation and differentiation occur when environmental heterogeneity decreases or increases, respectively. Fifth, species interactions can influence beta diversity via habitat modification, disease, consumption (trophic dynamics), competition, and by altering ecosystem productivity. Our synthesis highlights the multitude of mechanisms that cause assemblages to be more or less spatially similar in composition (taxonomically, functionally, phylogenetically) through time. We consider that future studies should aim to enhance our collective understanding of ecological systems by clarifying the underlying mechanisms driving homogenisation or differentiation, rather than focusing only on reporting the prevalence and direction of change in beta diversity, per se. biodiversity, beta diversity, biotic homogenisation, biotic differentiation, species assemblage, turnoverpublishedVersio

Immediate pre-meal water ingestion decreases voluntary food intake in lean young males

Purpose: Consuming 375-500 ml of water 30 min before a meal has been shown to reduce energy intake in older, but not younger adults. This study investigated the effects of ingesting a water preload immediately pre-meal (<1 min before eating) on within-meal ad-libitum energy intake in non-obese young males. Methods: Fourteen healthy males (mean (SD) age 27 (3) y, Height 1.83 (0.05) m, body weight 80.47 (9.89) kg, body fat 17.5 (4.0) %, body mass index 24.0 (2.5) kg/m2) completed a familiarisation trial and two experimental trials in randomised counterbalanced order. Subjects arrived at the laboratory overnight fasted and consumed an ad-libitum porridge breakfast. Immediately prior to the meal, subjects consumed either a 568 ml (1 pint) water preload (preload trial) or no preload (control trial). Visual analogue scale questionnaires to assess hunger, fullness and satisfaction were completed before and after the meal in both trials, as well as after the water preload. Results: Ad-libitum energy intake was greater (P<0.001) during control (2551 (562) kJ) than preload (1967 (454) kJ). Ad-libitum water intake was also greater (P<0.001) during control (318 (226-975) ml) than preload (116 (0-581) ml). The water preload increased fullness and satisfaction and decreased hunger compared to pre-trial (P<0.001) and the control trial (P<0.001). Conclusion: This study demonstrates that consumption of a 568 ml water preload immediately before a meal reduces energy intake in non-obese young males. This might therefore be an effective strategy to suppress energy intake in this population and possibly assist with weight management

Increased Sleep Fragmentation Leads to Impaired Off-Line Consolidation of Motor Memories in Humans

A growing literature supports a role for sleep after training in long-term memory consolidation and enhancement. Consequently, interrupted sleep should result in cognitive deficits. Recent evidence from an animal study indeed showed that optimal memory consolidation during sleep requires a certain amount of uninterrupted sleep

DEVELOPMENT AND TURBINE ENGINE PERFORMANCE OF THREE ADVANCED RHENIUM CONTAINING SUPERALLOYS FOR SINGLE CRYSTAL AND DIRECTIONALLY SOUDIFIED BLADES AND VANES

ABSTRACT Turbine inlet temperatures over the next few years will approach 1650°C (3000°F) at maximum power for the latest large commercial turbofan engines, resulting in high fuel efficiency and thrust levels approaching 445 kN (100,000 lbs). High reliability and durability must be intrinsically designed into these turbine engines to meet operating economic targets and ETOPS certification requirement This level of performance has been brought about by a combination of advances in air cooling for turbine blades and vanes, design technology for stresses and airflow, single crystal and directionally solidified casting process improvements and the development and use of rhenium (Re) containing high y&apos; volume fraction nickel-base superalloys with advanced coatings, including full-airfoil ceramic thermal bather coatings. Re additions to cast airfoil superalloys not only improve creep and thermo-mechanical fatigue strength but also environmental properties, including coating performance. Re dramatically slows down diffusion in these alloys at high operating temperatures. A team approach has been used to develop a family of two nickel-base single crystal alloys (CMSX-4. containing 3% Re and CMSX0-10 containing 6% Re) and a directionally solidified, columnar grain nickel-base alloy (CM 186 LC: containing 3% Re) for a variety of turbine engine applications. A range of critical properties of these alloys is reviewed in relation to turbine component engineering performance through engine certification testing and service experience. Industrial turbines are now commencing to use this aero developed turbine technology in both small and large frame units in addition to aero-derivative industrial engines. These applications are demanding with high reliability required for turbine airfoils out to 25,000 hours, with perhaps greater than 50% of the time spent at maximum power. Combined cycle efficiencies of large frame industrial engines is scheduled to reach 60% in the U.S. ATS programme. Application experience to a total 1.3 million engine hours and 28,000 hours individual blade set service for CMSX-4 first stage turbine blades is reviewed for a small frame industrial engine. INTRODUCTION During the last 30 years, turbine inlet temperatures have increased by about 500°C (900°F). About 70% of this increase is due to more efficient design of air cooling for turbine blades and vanes, particularly the advent of serpentine convection an

Reward vs non-reward sensitivity of the medial vs lateral orbitofrontal cortex relates to the severity of depressive symptoms

Background: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and non-reward is related to the severity of depressive symptoms. Methods: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at age 14 (n=1877) and 19 (n=1140) with a longitudinal design. Clinically-relevant subgroups were compared at age 19 (high-severity group n=116; low-severity group n=206), and 14. Results: The medial OFC exhibited graded activation increases to reward; and the lateral OFC had graded activation increases to non-reward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both age 14 and 19. In a stratified high-severity depressive symptom vs control comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to non-reward (No-Win) in the high-severity group at age 19 (p=0.027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both age 14 (p=0.002) and 19 (p=0.002). In a longitudinal design, there was greater sensitivity to non-reward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p=0.003). Conclusions: Activations in the lateral orbitofrontal cortex relate to sensitivity to not winning, were associated with high depressive symptom scores, and at 14 predicted the depressive symptoms at 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores

HNF4alpha Dysfunction as a Molecular Rational for Cyclosporine Induced Hypertension

Induction of tolerance against grafted organs is achieved by the immunosuppressive agent cyclosporine, a prominent member of the calcineurin inhibitors. Unfortunately, its lifetime use is associated with hypertension and nephrotoxicity. Several mechanism for cyclosporine induced hypertension have been proposed, i.e. activation of the sympathetic nervous system, endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in prostaglandin and nitric oxide, altered cytosolic calcium translocation, and activation of the renin-angiotensin system (RAS). In this regard the molecular basis for undue RAS activation and an increased signaling of the vasoactive oligopeptide angiotensin II (AngII) remain elusive. Notably, angiotensinogen (AGT) is the precursor of AngII and transcriptional regulation of AGT is controlled by the hepatic nuclear factor HNF4alpha. To better understand the molecular events associated with cyclosporine induced hypertension, we investigated the effect of cyclosporine on HNF4alpha expression and activity and searched for novel HNF4alpha target genes among members of the RAS cascade. Using bioinformatic algorithm and EMSA bandshift assays we identified angiotensin II receptor type 1 (AGTR1), angiotensin I converting enzyme (ACE), and angiotensin I converting enzyme 2 (ACE2) as genes targeted by HNF4alpha. Notably, cyclosporine represses HNF4alpha gene and protein expression and its DNA-binding activity at consensus sequences to AGT, AGTR1, ACE, and ACE2. Consequently, the gene expression of AGT, AGTR1, and ACE2 was significantly reduced as evidenced by quantitative real-time RT-PCR. While RAS is composed of a sophisticated interplay between multiple factors we propose a decrease of ACE2 to enforce AngII signaling via AGTR1 to ultimately result in vasoconstriction and hypertension. Taken collectively we demonstrate cyclosporine to repress HNF4alpha activity through calcineurin inhibitor mediated inhibition of nuclear factor of activation of T-cells (NFAT) which in turn represses HNF4alpha that leads to a disturbed balance of RAS

Recurrent, Robust and Scalable Patterns Underlie Human Approach and Avoidance

BACKGROUND. Approach and avoidance behavior provide a means for assessing the rewarding or aversive value of stimuli, and can be quantified by a keypress procedure whereby subjects work to increase (approach), decrease (avoid), or do nothing about time of exposure to a rewarding/aversive stimulus. To investigate whether approach/avoidance behavior might be governed by quantitative principles that meet engineering criteria for lawfulness and that encode known features of reward/aversion function, we evaluated whether keypress responses toward pictures with potential motivational value produced any regular patterns, such as a trade-off between approach and avoidance, or recurrent lawful patterns as observed with prospect theory. METHODOLOGY/PRINCIPAL FINDINGS. Three sets of experiments employed this task with beautiful face images, a standardized set of affective photographs, and pictures of food during controlled states of hunger and satiety. An iterative modeling approach to data identified multiple law-like patterns, based on variables grounded in the individual. These patterns were consistent across stimulus types, robust to noise, describable by a simple power law, and scalable between individuals and groups. Patterns included: (i) a preference trade-off counterbalancing approach and avoidance, (ii) a value function linking preference intensity to uncertainty about preference, and (iii) a saturation function linking preference intensity to its standard deviation, thereby setting limits to both. CONCLUSIONS/SIGNIFICANCE. These law-like patterns were compatible with critical features of prospect theory, the matching law, and alliesthesia. Furthermore, they appeared consistent with both mean-variance and expected utility approaches to the assessment of risk. Ordering of responses across categories of stimuli demonstrated three properties thought to be relevant for preference-based choice, suggesting these patterns might be grouped together as a relative preference theory. Since variables in these patterns have been associated with reward circuitry structure and function, they may provide a method for quantitative phenotyping of normative and pathological function (e.g., psychiatric illness).National Institute on Drug Abuse (14118, 026002, 026104, DABK39-03-0098, DABK39-03-C-0098); The MGH Phenotype Genotype Project in Addiction and Mood Disorder from the Office of National Drug Control Policy - Counterdrug Technology Assessment Center; MGH Department of Radiology; the National Center for Research Resources (P41RR14075); National Institute of Neurological Disorders and Stroke (34189, 05236

Simulating rewetting events in intermittent rivers and ephemeral streams: a global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56‐98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached organic matter. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events

Simulating rewetting events in intermittent rivers and ephemeral streams: A global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and the ex‐ tent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (precon‐ ditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experi‐ mentally simulated, under standard laboratory conditions, rewetting of leaves, river‐ bed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative character‐ istics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dis‐ solved substances during rewetting events (56%–98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contrib‐ uted most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental vari‐ ables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached sub‐ stances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying event