Genetic Background Influences Behavior and Responses to Epigenetic Changes Induced by a Methyl-Donor Diet

With recent strides in epigenetics, mainstream media informs the public that we can “beat our genes” by, for instance, changing our diet. Genetics, however, still plays a role in phenotype. Folate and other methyl-donor pathway components are widely supplemented due to their ability to prevent neural tube defects during prenatal development. In addition to vitamins, these compounds are also added to commercial flour, energy drinks, and other supplements. Several lines of evidence suggest that these supplements act through epigenetic mechanisms, including altering DNA methylation. Increasing evidence suggests potential deleterious effects of excessive folate. Given the benefits of these compounds, risk statements must be made with caution. We hypothesized that excess dietary methyl donors during development might contribute to the apparent rise in neurobehavioral disorders such as attention-deficit disorder (ADD), obsessive compulsive disorder (OCD) and autism spectrum disorders (ASD). To test these hypotheses, we used wildderived Peromyscus (deer mice) stocks. Peromyscus are common native North American mammals and exhibit great natural variation. We used two species that are known to differ in physiology, epigenetic control, and behavior. Specifically, P. maniculatus (BW stock) are susceptible to repetitive behaviors and are more aggressive in a neutral space. P. polionotus (PO stock) exhibit greater sociality and less repetitive behavior and are better able to buffer stress. In addition the two species can form fertile hybrids in BW female x PO male crosses thus enabling genetic basis of such phenotypes to be determined. Here we have determined genetic mechanisms by which behaviors differ between BW and PO. Additionally, we discovered behavioral differences in a naturally occurring wide band agouti (ANb) deer mouse (on a BW background) when compared to BW. Using the same methyl-donor diet used in the classic mouse agouti viable yellow allele (Avy), we demonstrated that the effects of the diet are different across three genotypes (while two genotypes, BW and ANb, are very similar). These effects included various adult defects, mortality, and behavioral changes. Here we also present data from additional behavioral parameters in both PO and BW animals developmentally exposed to the methyldonor diet. We also present data showing paternal genotype affects DNA methylation status at the imprinting control region of the Peg10/Sgce locus. This work was funded by NIH P40 OD 010961 and by a SPARC Grant from the Office of the VP for Research at the University of South Carolina

Novel pharmacotherapeutic treatments for cocaine addiction

Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and serotonin in the brain due to prevention of their re-uptake into the neuron that released the neurotransmitter. Cocaine dependence is a public health concern and cause of significant morbidity and mortality worldwide. At present, there are no approved medications for the treatment of this devastating illness, and behavioral interventions have proven to be of limited use. However, there have been a number of recent trials testing promising agents including dopamine agonists, GABAergic medications and the cocaine vaccine. Here we discuss the most recent human clinical trials of potential medications for treatment of cocaine dependence, as well as pre-clinical studies for another promising agent, levo tetrahydropalmatine. Examination of these recent findings shows promise for GABAergic medications and the cocaine vaccine, as well as unique medications such as disulfiram, whose mechanism remains to be determined. Future work may also confirm specific subgroups of patients for treatment response based on clinical characteristics, biomarkers and pharmacogenetics. This review highlights the need for further, bigger studies in order to determine optimal clinical usage

KINETIC AND KINEMATIC CHANGES ASSOCIATED WITH ALTERING HEEL HEIGHT DURING CRICKET MEDIUM-FAST BOWLING

INTRODUCTION: During a cricket bowling delivery, the major impact with the pitch occurs at front foot impact (FFI), generating forces approximately 5.7 times body weight (BW) in the vertical plane and 3.5 BW in the horizontal plane. (Hurrion et al. 2000). Although cricket footwear has been acknowledged by researchers as worthy of investigation, to date there is no research published to inform of the potential for injury prevention. Bartold (2005) found when investigating midsole height in football footwear that a graduated rise of 1cm altered lower limb muscle activity and reduced peak pressures under the foot during treadmill running. Associated altered kinematics reported by Bartold (2005) is in accordance with reports by Eslami et al. (2005) who found a 0.4cm posterior wedge can be utilised to alter the angular variability of the subtalar joint and its proximal joints and segments in their respective planes of movement during single limb stance

Multi-environment QTL mixed models for drought stress adaptation in wheat

Many quantitative trait loci (QTL) detection methods ignore QTL-by-environment interaction (QEI) and are limited in accommodation of error and environment-specific variance. This paper outlines a mixed model approach using a recombinant inbred spring wheat population grown in six drought stress trials. Genotype estimates for yield, anthesis date and height were calculated using the best design and spatial effects model for each trial. Parsimonious factor analytic models best captured the variance-covariance structure, including genetic correlations, among environments. The 1RS.1BL rye chromosome translocation (from one parent) which decreased progeny yield by 13.8 g m(-2) was explicitly included in the QTL model. Simple interval mapping (SIM) was used in a genome-wide scan for significant QTL, where QTL effects were fitted as fixed environment-specific effects. All significant environment-specific QTL were subsequently included in a multi-QTL model and evaluated for main and QEI effects with non-significant QEI effects being dropped. QTL effects (either consistent or environment-specific) included eight yield, four anthesis, and six height QTL. One yield QTL co-located (or was linked) to an anthesis QTL, while another co-located with a height QTL. In the final multi-QTL model, only one QTL for yield (6 g m(-2)) was consistent across environments (no QEI), while the remaining QTL had significant QEI effects (average size per environment of 5.1 g m(-2)). Compared to single trial analyses, the described framework allowed explicit modelling and detection of QEI effects and incorporation of additional classification information about genotypes

KINETIC AND KINEMATIC CHANGES ASSOCIATED WITH ALTERING HEEL HEIGHT DURING CRICKET MEDIUM-FAST BOWLING

INTRODUCTION: During a cricket bowling delivery, the major impact with the pitch occurs at front foot impact (FFI), generating forces approximately 5.7 times body weight (BW) in the vertical plane and 3.5 BW in the horizontal plane. (Hurrion et al. 2000). Although cricket footwear has been acknowledged by researchers as worthy of investigation, to date there is no research published to inform of the potential for injury prevention. Bartold (2005) found when investigating midsole height in football footwear that a graduated rise of 1cm altered lower limb muscle activity and reduced peak pressures under the foot during treadmill running. Associated altered kinematics reported by Bartold (2005) is in accordance with reports by Eslami et al. (2005) who found a 0.4cm posterior wedge can be utilised to alter the angular variability of the subtalar joint and its proximal joints and segments in their respective planes of movement during single limb stance. This study looks at the effect of within shoe heel raises upon ground front foot impact forces. It is believed that by raising the rearfoot in relation to the forefoot, the windlass mechanism will be elicited, increasing medial longitudinal arch height to further improve the shock attenuation properties of the foot, and thus lower the stresses higher up in the kinetic chain

Coloration as an indicator of male quality in the dark-winged damselfly Calopteryx maculata

Natural History & EvolutionCalopteryx maculata, commonly known as the dark-winged damselfly, mate in a system based on quality of ovipositing patches. It has been observed in Europe that this genus uses a series of pre- and post-copulatory behavioral displays where males face females while showing their pigmented wings to indicate quality (Cordoba-Aguilar 2001). It may be possible that the iridescent coloration in the dark-winged damselfly can function as ornaments since fat-stores determine coloration and endurance in territory battles in the North American species, which hasn’t been investigated previously. Fifteen pairs of mating and non-mating territorial males were caught and their abdomens were analyzed using a spectral optics program to determine if coloration was an indictor of mating status. Our results did not support the hypothesis, and coloration was not significantly correlated to mating status. The only significant result was a linear regression between body weight and coloration, the larger size corresponding to a lower spectrum wavelength. It appears that coloration does not correlate with female mating preference in Calopteryx maculata, but males who operate under an alternative reproductive strategy, sneaking, were not tested in this experiment, and could potentially change the distribution of the results.http://deepblue.lib.umich.edu/bitstream/2027.42/57583/1/Shorter_John_2007.pd

Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase.

Bacterial ClpB and yeast Hsp104 are homologous Hsp100 protein disaggregases that serve critical functions in proteostasis by solubilizing protein aggregates. Two AAA+ nucleotide binding domains (NBDs) power polypeptide translocation through a central channel comprised of a hexameric spiral of protomers that contact substrate via conserved pore-loop interactions. Here we report cryo-EM structures of a hyperactive ClpB variant bound to the model substrate, casein in the presence of slowly hydrolysable ATPγS, which reveal the translocation mechanism. Distinct substrate-gripping interactions are identified for NBD1 and NBD2 pore loops. A trimer of N-terminal domains define a channel entrance that binds the polypeptide substrate adjacent to the topmost NBD1 contact. NBD conformations at the seam interface reveal how ATP hydrolysis-driven substrate disengagement and re-binding are precisely tuned to drive a directional, stepwise translocation cycle