Dysregulation of Lipid and Glucose Homeostasis in Hepatocyte-Specific SLC25A34 Knockout Mice.

Nonalcoholic fatty liver disease (NAFLD) is an epidemic affecting 30% of the US population. It is characterized by insulin resistance, and by defective lipid metabolism and mitochondrial dysfunction in the liver. SLC25A34 is a major repressive target of miR-122, a miR that has a central role in NAFLD and liver cancer. However, little is known about the function of SLC25A34. To investigate SLC25A34 in vitro, mitochondrial respiration and bioenergetics were examined using hepatocytes depleted of Slc25a34 or overexpressing Slc25a34. To test the function of SLC25A34 in vivo, a hepatocyte-specific knockout mouse was generated, and loss of SLC25A34 was assessed in mice maintained on a chow diet and a fast-food diet (FFD), a model for NAFLD. Hepatocytes depleted of Slc25a34 displayed increased mitochondrial biogenesis, lipid synthesis, and ADP/ATP ratio; Slc25a34 overexpression had the opposite effect. In the knockout model on chow diet, SLC25A34 loss modestly affected liver function (altered glucose metabolism was the most pronounced defect). RNA-sequencing revealed changes in metabolic processes, especially fatty acid metabolism. After 2 months on FFD, knockouts had a more severe phenotype, with increased lipid content and impaired glucose tolerance, which was attenuated after longer FFD feeding (6 months). This work thus presents a novel model for studying SLC25A34 in vivo in which SLC25A34 plays a role in mitochondrial respiration and bioenergetics during NAFLD.

In-kennel behavior predicts length of stay in shelter dogs.

Previous empirical evaluations of training programs aimed at improving dog adoption rates assume that dogs exhibiting certain behaviors are more adoptable. However, no systematic data are available to indicate that the spontaneous behavior of shelter dogs has an effect on adopter preference. The aim of the present study was to determine whether any behaviors that dogs exhibit spontaneously in the presence of potential adopters were associated with the dogs' length of stay in the shelter. A sample of 289 dogs was videotaped for 1 min daily throughout their stay at a county shelter. To account for differences in adopter behavior, experimenters varied from solitary passive observers to pairs of interactive observers. Dogs behaved more attentively to active observers. To account for adopter preference for morphology, dogs were divided into "morphologically preferred" and "non-preferred" groups. Morphologically preferred dogs were small, long coated, ratters, herders, and lap dogs. No theoretically significant differences in behavior were observed between the two different dog morphologies. When accounting for morphological preference, three behaviors were found to have a significant effect on length of stay in all dogs: leaning or rubbing on the enclosure wall (increased median length of stay by 30 days), facing away from the front of the enclosure (increased by 15 days), and standing (increased by 7 days). When combinations of behaviors were assessed, back and forth motion was found to predict a longer stay (increased by 24 days). No consistent behavioral changes were observed due to time spent at the shelter. These findings will allow shelters to focus behavioral modification efforts only on behaviors likely to influence adopters' choices.

Modeling human methamphetamine exposure in nonhuman primates: chronic dosing in the rhesus macaque leads to behavioral and physiological abnormalities.

Acute high dose methamphetamine (METH) dosing regimens are frequently used in animal studies, however, these regimens can lead to considerable toxicity and even death in experimental animals. Acute high dosing regimens are quite distinct from the chronic usage patterns found in many human METH abusers. Furthermore, such doses, especially in nonhuman primates, can result in unexpected death, which is unacceptable, especially when such deaths fail to accurately model effects of human usage. As a model of chronic human METH abuse we have developed a nonlethal chronic METH administration procedure for the rhesus macaque that utilizes an escalating dose protocol. This protocol slowly increases the METH dosage from 0.1 to 0.7 mg/kg b.i.d. over a period of 4 weeks, followed by a period of chronic METH administration at 0.75 mg/kg b.i.d. (= total daily METH administration of 1.5 mg/kg). In parallel to human usage patterns, METH injections were given 20-23 times a month. This regimen produced a number of behavioral and physiological effects including decreased food intake and a significant increase in urinary cortisol excretion.