No trans-generational maternal effects of early-life corticosterone exposure on neophobia and antipredator behaviour in the house sparrow

Journal of Ethology - Conditions experienced during early development can lead to profound long-lasting changes in physiology and behaviour. The extent to which such “programming”...     

Identification of pyridazin-3-one derivatives as potent, selective histamine H₃ receptor inverse agonists with robust wake activity

H(3)R structure-activity relationships on a novel class of pyridazin-3-one H(3)R antagonists/inverse agonists are disclosed. Modifications of the pyridazinone core, central phenyl ring and linker led to the identification of molecules with excellent target potency, selectivity and pharmacokinetic properties. Compounds 13 and 21 displayed potent functional H(3)R antagonism in vivo in the rat dipsogenia model and demonstrated robust wake activity in the rat EEG/EMG model.     

Relationships of maternal body size and morphology with egg and clutch size in the diamondback terrapin,Malaclemys terrapin (Testudines: Emydidae)

Because resources are finite, female animals face trade‐offs between the size and number of offspring they are able to produce during a single reproductive event. Optimal egg size (OES) theory predicts that any increase in resources allocated to reproduction should increase clutch size with minimal effects on egg size. Variations of OES predict that egg size should be optimized, although not necessarily constant across a population, because optimality is contingent on maternal phenotypes, such as body size and morphology, and recent environmental conditions. We examined the relationships among body size variables (pelvic aperture width, caudal gap height, and plastron length), clutch size, and egg width of diamondback terrapins from separate but proximate populations at Kiawah Island and Edisto Island, South Carolina. We found that terrapins do not meet some of the predictions of OES theory. Both populations exhibited greater variation in egg size among clutches than within, suggesting an absence of optimization except as it may relate to phenotype/habitat matching. We found that egg size appeared to be constrained by more than just pelvic aperture width in Kiawah terrapins but not in the Edisto population. Terrapins at Edisto appeared to exhibit osteokinesis in the caudal region of their shells, which may aid in the oviposition of large eggs.     

MNK1 and MNK2 regulation in HER2-overexpressing breast cancer lines

MAPK-interacting protein kinases 1 and 2 (MNK1 and MNK2) function downstream of p38 and ERK MAPK, but there are large gaps in our knowledge of how MNKs are regulated and function. As proteins activated in the HER2/Ras/Raf/ERK pathway, the MNKs are of potential interest in HER2-overexpressing cancers. We utilized a panel of breast cell lines (HCC1419, AU565, SKBR3, MCF7, and MCF10A), three of which overexpress HER2, to characterize the amounts and activation status of MNKs and other pathway enzymes (ERKs and RSKs) in these cells. We generated a phosphospecific antibody to Thr(P)-214 in the T-loop of MNKs and found that phosphorylations of both Thr-209 and Thr-214 in human MNK1 are required for activation. Increased phosphorylation and activity of the MNKs correlate with HER2 overexpression, and inhibition of the MNKs reduces colony formation in soft agar. Our work identifies the MNKs as potential therapeutic targets for breast cancer treatments.     

Polyunsaturated fat in the methionine-choline-deficient diet influences hepatic inflammation but not hepatocellular injury

Methionine-choline-deficient (MCD) diets that cause steatohepatitis in rodents are typically enriched in polyunsaturated fat. To determine whether the fat composition of the MCD formula influences the development of liver disease, we manufactured custom MCD formulas with fats ranging in PUFA content from 2% to 59% and tested them for their ability to induce steatohepatitis. All modified-fat MCD formulas caused identical degrees of hepatic steatosis and resulted in a similar distribution of fat within individual hepatic lipid compartments. The fatty acid composition of hepatic lipids, however, reflected the fat composition of the diet. Mice fed a PUFA-rich MCD formula showed extensive hepatic lipid peroxidation, induction of proinflammatory genes, and histologic inflammation. When PUFAs were substituted with more saturated fats, lipid peroxidation, proinflammatory gene induction, and hepatic inflammation all declined significantly. Despite the close relationship between PUFAs and hepatic inflammation in mice fed MCD formulas, dietary fat had no impact on MCD-mediated damage to hepatocytes. Indeed, histologic apoptosis and serum alanine aminotransferase levels were comparable in all MCD-fed mice regardless of dietary fat content. Together, these results indicate that dietary PUFAs promote hepatic inflammation but not hepatotoxicity in the MCD model of liver disease. These findings emphasize that individual dietary nutrients can make specific contributions to steatohepatitis.     

Evaluation by Expert Dancers of a Robot That Performs Partnered Stepping via Haptic Interaction

Our long-term goal is to enable a robot to engage in partner dance for use in rehabilitation therapy, assessment, diagnosis, and scientific investigations of two-person whole-body motor coordination. Partner dance has been shown to improve balance and gait in people with Parkinson''s disease and in older adults, which motivates our work. During partner dance, dance couples rely heavily on haptic interaction to convey motor intent such as speed and direction. In this paper, we investigate the potential for a wheeled mobile robot with a human-like upper-body to perform partnered stepping with people based on the forces applied to its end effectors. Blindfolded expert dancers (N=10) performed a forward/backward walking step to a recorded drum beat while holding the robot''s end effectors. We varied the admittance gain of the robot''s mobile base controller and the stiffness of the robot''s arms. The robot followed the participants with low lag (M=224, SD=194 ms) across all trials. High admittance gain and high arm stiffness conditions resulted in significantly improved performance with respect to subjective and objective measures. Biomechanical measures such as the human hand to human sternum distance, center-of-mass of leader to center-of-mass of follower (CoM-CoM) distance, and interaction forces correlated with the expert dancers'' subjective ratings of their interactions with the robot, which were internally consistent (Cronbach''s α=0.92). In response to a final questionnaire, 1/10 expert dancers strongly agreed, 5/10 agreed, and 1/10 disagreed with the statement "The robot was a good follower." 2/10 strongly agreed, 3/10 agreed, and 2/10 disagreed with the statement "The robot was fun to dance with." The remaining participants were neutral with respect to these two questions.     

Characterization of Soluble Hepatitis C Virus RNA-Dependent RNA Polymerase Expressed in Escherichia coli

Production of soluble full-length nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) has been shown to be problematic and requires the addition of salts, glycerol, and detergents. In an effort to improve the solubility of NS5B, the hydrophobic C terminus containing 21 amino acids was removed, yielding a truncated NS5B (NS5BΔCT) which is highly soluble and monodispersed in the absence of detergents. Fine deletional analysis of this region revealed that a four-leucine motif (LLLL) in the hydrophobic domain is responsible for the solubility profile of the full-length NS5B. Enzymatic characterization revealed that the RNA-dependent RNA polymerase (RdRp) activity of this truncated NS5B was comparable to those reported previously by others. For optimal enzyme activity, divalent manganese ions (Mn²⁺) are preferred rather than magnesium ions (Mg²⁺), whereas zinc ions (Zn²⁺) inhibit the RdRp activity. Gliotoxin, a known poliovirus 3D RdRp inhibitor, inhibited HCV NS5B RdRp in a dose-dependent manner. Kinetic analysis revealed that HCV NS5B has a rather low processivity compared to those of other known polymerases.     

Time dependent cadmium uptake by fathead minnows (Pimephales promelas) during field and laboratory exposure

Fathead minnows (Pimephales promelas) exposed to 2.5 ppb cadmium in an industrially contaminated lake accumulated whole body burdens of 3.19 ppm Cd in 12 hours, while minnows exposed to 48 ppb Cd in a continuous flow laboratory system did not reach comparable levels until the eighth day of exposure. Significant whole body accumulation of Cd (approximately 9 ppm) peaked within 17–20 days of exposure in the laboratory.