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.     

Characterization of long RNA-cleaving deoxyribozymes with short catalytic cores: the effect of excess sequence elements on the outcome of in vitro selection

We previously conducted an in vitro selection experiment for RNA-cleaving deoxyribozymes, using a combinatorial DNA library containing 80 random nucleotides. Ultimately, 110 different sequence classes were isolated, but the vast majority contained a short14-15 nt catalytic DNA motif commonly known as 8-17. Herein, we report extensive truncation experiments conducted on multiple sequence classes to confirm the suspected catalytic role played by 8-17 and to determine the effect of excess sequence elements on the activity of this motif and the outcome of selection. Although we observed beneficial, detrimental and neutral consequences for activity, the magnitude of the effect rarely exceeded 2-fold. These deoxyribozymes appear to have survived increasing selection pressure despite the presence of additional sequence elements, rather than because of them. A new deoxyribozyme with comparable activity, called G15-30, was approximately 2.5-fold larger and experienced a approximately 4-fold greater inhibitory effect from excess sequence elements than the average 8-17 motif. Our results suggest that 8-17 may be less susceptible to the potential inhibitory effects of excess arbitrary sequence than larger motifs, which represents a previously unappreciated selective advantage that may contribute to its widespread recurrence.     

Mechanical similarity across ontogeny of digging muscles in an Australian marsupial (Isoodon fusciventer)

Many mammals dig, either during foraging to access subsurface food resources, or in creating burrows for shelter. Digging requires large forces produced by muscles and transmitted to the soil via the skeletal system; thus fossorial mammals tend to have characteristic modifications of the musculoskeletal system that reflect their digging ability. Bandicoots (Marsupialia: Peramelidae) scratch-dig mainly to source food, searching for subterranean food items including invertebrates, seeds, and fungi. They have musculoskeletal features for digging, including shortened, robust forelimb bones, large muscles, and enlarged muscle attachment areas. Here, we compared changes in the ontogenetic development of muscles associated with digging in the Quenda (Isoodon fusciventer). We measured muscle mass (m _m), pennation angle, and fiber length (FL) to calculate physiological cross-sectional area (PCSA; a proxy of maximum isometric force) as well as estimate the maximum isometric force (Fmax) for 34 individuals ranging in body size from 124 to 2,390 g. Males grow larger than females in this bandicoot species, however, we found negligible sex differences in mass-specific m _m, PCSA or FL for our sample. Majority of the forelimb muscles PCSA showed a positive allometric relationship with total body mass, while m _m and FL in the majority of forelimb muscles showed isometry. Mechanical similarity was tested, and two thirds of forelimb muscles maximum isometric forces (Fmax) scaled with isometry; therefore the forelimb is primarily mechanical similar throughout ontogeny. PCSA showed a significant difference between scaling slopes between main movers in the power stroke, and main movers of the recovery stroke of scratch-digging. This suggests that some forelimb muscles grow with positive allometry, specially these associated with the power stroke of digging. Intraspecific variation in PCSA is rarely considered in the literature, and thus this is an important study quantifying changes in muscle architectural properties with growth in a mammalian model of scratch-digging.     

BOO! Culture, Experience, and the Startle Reflex

BOO! Culture, Experience, and the Startle Reflex. Ronald C. Simons. New York and Oxford, England: Oxford University Press, 1996. 272 pp.     

Some stochastic features of bacterial constant growth apparatus

Stochastic models for bacterial constant growth apparatus such as the chemostat are posed and studied. Approximations are given for the mean and variance of the size of the bacterial population when the population is in steady state. Procedures for stimulating a chemostat are developed and the approximate moments are compared with simulated values. The distribution is derived for the waiting time until the occurrence of a population change-over to a faster growing strain. Research supported by National Institutes of Health Grant 5-R01-GM21214.