Reward Mechanisms in Obesity: New Insights and Future Directions

Food is consumed in order to maintain energy balance at homeostatic levels. In addition, palatable food is also consumed for its hedonic properties independent of energy status. Such reward-related consumption can result in caloric intake exceeding requirements and is considered a major culprit in the rapidly increasing rates of obesity in developed countries. Compared with homeostatic mechanisms of feeding, much less is known about how hedonic systems in brain influence food intake. Intriguingly, excessive consumption of palatable food can trigger neuroadaptive responses in brain reward circuitries similar to drugs of abuse. Furthermore, similar genetic vulnerabilities in brain reward systems can increase predisposition to drug addiction and obesity. Here, recent advances in our understanding of the brain circuitries that regulate hedonic aspects of feeding behavior will be reviewed. Also, emerging evidence suggesting that obesity and drug addiction may share common hedonic mechanisms will also be considered

Food addiction: a valid concept?

Can food be addictive? What does it mean to be a food addict? Do common underlying neurobiological mechanisms contribute to drug and food addiction? These vexing questions have been the subject of considerable interest and debate in recent years, driven in large part by the major health concerns associated with dramatically increasing body weights and rates of obesity in the United States, Europe, and other regions with developed economies. No clear consensus has yet emerged on the validity of the concept of food addiction and whether some individuals who struggle to control their food intake can be considered food addicts. Some, including Fletcher, have argued that the concept of food addiction is unsupported, as many of the defining features of drug addiction are not seen in the context of feeding behaviors. Others, Kenny included, have argued that food and drug addiction share similar features that may reflect common underlying neural mechanisms. Here, Fletcher and Kenny argue the merits of these opposing positions on the concept of food addiction.Wellcome Trust Bernard Wolfe Health Neurosciencce Fund National Institutes of Health, US

Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: pharmacological and behavioral genetics evidence.

Considerable evidence suggests that transmission at hypocretin-1 (orexin-1) receptors (Hcrt-R1) plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV) cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS) thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg) dose-dependently decreased cocaine (0.5 mg/kg/infusion) self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg) also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg) on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts

Validating performance of automotive materials at high strain rate for improved crash design

This paper investigates sources of performance variability in high velocity testing of automotive crash structures. Sources of variability, or so called noise factors, present in a testing environment, arise from uncertainty in structural properties, joints, boundary conditions and measurement system. A box structure, which is representative of a crash component, is designed and fabricated from a high strength Dual Phase sheet steel. Crush tests are conducted at low and high speed. Such tests intend to validate a component model and material strain rate sensitivity data determined from high speed tensile testing. To support experimental investigations, stochastic modeling is used to investigate the effect of noise factors on crash structure performance variability, and to identify suitable performance measures to validate a component model and material strain rate sensitivity data. The results of the project will enable the measurement of more reliable strain rate sensitivity data for improved crashworthiness predictions of automotive structures

Attitude Determination and Launch Diagnostics for a Picosat via Kalman Filtering of Magnetometer Data

The picosat is a hockey puck sized spinning spacecraft with a two-axis ring core \u27fluxgate magnetometer. The purpose of the picosat project is to demonstrate the technologies required to take simultaneous spatially distributed measurements of fields and particles with very small spacecraft. The on-board magnetometer supports this purpose by validating the field measurement objective, and by providing attitude dynamics information for use in evaluating the launch mechanism/procedure. The paper presents methods developed for picosat attitude determination and dynamic modeling using data from the two-axis fluxgate magnetometer. Several picosat launch anomaly scenarios will be characterized to facilitate evaluation of the on-orbit performance of the launch system

ShapeCoder: Discovering Abstractions for Visual Programs from Unstructured Primitives

We introduce ShapeCoder, the first system capable of taking a dataset of shapes, represented with unstructured primitives, and jointly discovering (i) useful abstraction functions and (ii) programs that use these abstractions to explain the input shapes. The discovered abstractions capture common patterns (both structural and parametric) across a dataset, so that programs rewritten with these abstractions are more compact, and suppress spurious degrees of freedom. ShapeCoder improves upon previous abstraction discovery methods, finding better abstractions, for more complex inputs, under less stringent input assumptions. This is principally made possible by two methodological advancements: (a) a shape-to-program recognition network that learns to solve sub-problems and (b) the use of e-graphs, augmented with a conditional rewrite scheme, to determine when abstractions with complex parametric expressions can be applied, in a tractable manner. We evaluate ShapeCoder on multiple datasets of 3D shapes, where primitive decompositions are either parsed from manual annotations or produced by an unsupervised cuboid abstraction method. In all domains, ShapeCoder discovers a library of abstractions that captures high-level relationships, removes extraneous degrees of freedom, and achieves better dataset compression compared with alternative approaches. Finally, we investigate how programs rewritten to use discovered abstractions prove useful for downstream tasks

Exploring the epigenetics of cocaine resistance

Drug addiction is known to have a heritable component and to run in families. However, a recent study in rats by Vassoler et al.(1) shows an unexpected result-that the sons of males who had self-administered cocaine had a reduced propensity to take this drug and a delay in their acquisition of drug-seeking behavior. The authors linked these behavioral changes to epigenetic changes in the sperm from cocaine-exposed males and in the brains of their male offspring. We asked four experts to comment on the results of this study and their implications for understanding how addictive phenotypes are inherited

Interaction of C-60 molecules on Si(100)

The interactions between pairs of C60 molecules adsorbed upon the Si(1 0 0) surface have been studied via a series of DFT calculations. Configurations which have the fullerene cage located within the dimer trench bonded to four dimers (t4) have been investigated, as these have previously been found to be among the most stable for the C60 molecule. These t4 configurations are explored with all possible pairs of fullerene configuration combinations considered. We have looked at two distinct groups of separation distances between the two C60 molecules. These have the fullerene bonding sites as either adjacent to one another or separated by one Si surface dimer. Comparisons between the two groups confirm the trend of the combinations becoming more favourable at a greater fullerene separation. In the systems with adjacent bonding sites the combined pair of fullerenes were in general less favourable than the two isolated cases. At the longer fullerene separation distance this trend was reversed. The longer fullerene separation distance reflects the experimental separation observed by Moriarty et al. [P. Moriarty, Y.R. Ma, M.D. Upward, P.H. Beton, Surf. Sci. 407 (1998) 27]

A comparison of Colletotrichum species associated with berry diseases of Coffea arabica L.

Forty isolates of Colletotrichum species associated with coffee berry anthracnose in Papua New Guinea were characterised and identified on the basis of cultural, morphological and molecular characteristics. Of these, 29 isolates were identified as C. gloeosporioides, while the 11 remaining were identified as C. acutatum. None of the isolates had characteristics common to C. kahawae