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Large lecture courses are an efficient way to convey material to many students but have potential limitations, most notably the tendency for them to promote passive learning opportunities rather than active pedagogies. The curriculum at Cummings School of Veterinary Medicine at Tufts University, like many veterinary schools, contains many large lecture courses in the pre-clinical curriculum. This objective of this study was to use two active pedagogical interventions in a first-year lecture course named Veterinary Biochemistry and Metabolism that drew connections between basic science and several veterinary diseases. The first intervention targeted increasing students' intrinsic motivation and their confidence with understanding biochemistry concepts using videos created via collaborations between students, staff, and clinical and basic science faculty. The second intervention targeted active and collaborative learning via the implementation of clinical case studies completed in groups to relate lecture content to clinical scenarios with the aim of further enhancing student confidence in their knowledge of the material. To assess the effectiveness of these two interventions, pre-and post-course surveys using Likert style questions were administered to evaluate student confidence in the targeted concepts. The post-survey included open-ended responses on students' perspectives on their most important takeaways from the activities and their suggestions for improvements. The data showed a positive impact of these interventions on student motivation and confidence in their knowledge. This study provides support that targeted interventions to increase active learning strategies increase student engagement and may improve learning efficacy in large lecture courses.

Discusses the role of the laity in graduate education at a Catholic Jesuit university. (SWM)

Cyclic AMP (cAMP) induces translocation of multidrug resistant protein 2 (Mrp2) to the canalicular membrane and activates p38 MAPK in rat hepatocytes. In this study, we tested the hypothesis that cAMP-induced Mrp2 translocation may be mediated via p38 MAPK. Studies were conducted in rat hepatocytes and in a human hepatoma cell line, HUH-7. In rat hepatocytes, cAMP increased Mrp2 translocation and p38 MAPK activity. These effects of cAMP were inhibited by SB203580, an inhibitor of p38 MAPK. Wortmannin, a specific inhibitor of phosphoinositide-3-kinase (PI3K), did not inhibit cAMP induced activation of p38 MAPK, indicating PI3K-independent activation of p38 MAPK by cAMP. To further define the role of p38 MAPK, molecular approaches were used to up- or downregulate p38 MAPK activity in HUH-7 cells using constitutively active (CA) and dominant-negative (DN) MAPK kinase 3 and 6 (MKK3/6). MKK3/6 are upstream kinases responsible for the activation of p38 MAPK. Cells transfected with CAMKK6 showed increased p38 MAPK activity and MRP2 translocation compared with empty vector, cAMP-induced activation of p38 MAPK was inhibited in cells transfected with DNMKK3/6 and DNMKK3, but not with DNMKK6. DNMKK3/6 and DNMKK3 also inhibited cAMP-induced MRP2 translocation, cAMP selectively activated p38[alpha] MAPK in HUH-7 cells. Knockdown of p38[alpha] MAPK by short heterodimer RNA resulted in decreased level of p38 MAPK and failure of cAMP to stimulate MRP2 translocation. Taken together, these results suggest that cAMP-induced MRP2 translocation in hepatic cells is mediated via PI3K-independent and MKK3-mediated activation of p38[alpha] MAPK. p38 MAPK isoforms; rat hepatocytes; Huh-7 cells; MAPK kinase; phosphoinositide-3-kinase doi: 10.1152/ajpgi.00506.2009.

Schonhoff CM, Yamazaki A, Hohenester S, Webster CRL, Bouscarel B, Anwer MS. PKC[epsilon]-dependent and -independent effects of taurolithocholate on PI3K/PKB pathway and taurocholate uptake in HuH-NTCP cell line. Am J Physiol Gastrointest Liver Physiol 297: G1259-G1267, 2009. First published October 8, 2009; doi:10 .1152/ajpgi.00177.2009.--The cholestatic bile acid taurolithocholate (TLC) inhibits biliary secretion of organic anions and hepatic uptake of taurocholate (TC). TLC has been suggested to induce retrieval of Mrp2 from the canalicular membrane via the phosphoinositide-3-kinase (PI3K)/PKB-dependent activation of novel protein kinase C[epsilon] (nPKC[epsilon]) in rat hepatocytes. The aim of the present study was to determine whether TLC-induced inhibition of TC uptake may also involve PI3K-dependent activation of PKC[epsilon] in HuH7 cells stably transfected with human [Na.sup.+]-dependent TC-cotransporting polypeptide (NTCP) (HuH-NTCP cells). To avoid direct competition for uptake, cells were pretreated with TLC, washed, and then incubated with [.sup.3]H-TC to determine TC uptake. TLC produced time- and dose-dependent inhibition of TC uptake. TLC inhibited TC uptake competitively without affecting NTCP membrane translocation. A PI3K inhibitor failed to reverse TLC-induced TC uptake inhibition and TLC-inhibited PKB phosphorylation. TLC did activate nPKC[epsilon] as evidenced by increased membrane translocation and nPKC[epsilon]-[Ser.sup.729] phosphorylation. Overexpression of dominant negative-nPKC[epsilon] reversed TLC-induced inhibition of PKB phosphorylation but not of TC uptake. Finally, cAMP prevented TLC-induced inhibition of TC uptake via the PI3K pathway, and the prevention is due to the sum of cAMP-induced stimulation and TLC-induced inhibition of TC uptake. Taken together, these results suggest that TLC-induced inhibition of PKB, but not of TC uptake, is mediated via nPKC[epsilon]. Activation of nPKC[epsilon] and inhibition of TC uptake by TLC are not mediated via the PI3K/PKB pathway. dominant negative-novel protein kinase C[epsilon]; inhibition kinetics; PKB/ Akt; [Na.sup.+]-dependent tanrocholate-cotransporting polypeptide; phosphoinositide-3-kinase doi: 10.1152/ajpgi.00177.2009

Research has been conducted on nitric oxide and its S-nitrosylation effects on cysteine residues. The hypothesis that nitric oxide controls p53 via S-nitrosylation and activation of p53 negative inhibitor Hdm2 has been tested and the results demonstrate that cysteine residue mutation from a cysteine to an alanine eliminates Hdn2 sensitivity to nitric oxide inactivation.

Worldwide consumption of opioids remains at historic levels. Preclinical studies report intergenerational effects on the endogenous opioid system of future progeny following preconception morphine exposure. Given the role of endogenous opioids in energy homeostasis, such effects could impact metabolism in the next generation. Thus, we examined diet-induced modifications in F1 male progeny of morphine-exposed female rats (MORF1). When fed a high fat-sugar diet (FSD) for 6 weeks, MORF1 males display features of emerging metabolic syndrome; they consume more food, gain more weight, and develop fasting-induced hyperglycemia and hyperinsulinemia. In the hypothalamus, proteins involved in energy homeostasis are modified and RNA sequencing revealed down-regulation of genes associated with neuronal plasticity, coupled with up-regulation of genes associated with immune, inflammatory, and metabolic processes that are specific to FSD-maintained MORF1 males. Thus, limited preconception morphine exposure in female rats increases the risk of metabolic syndrome/type 2 diabetes in the next generation. [ABSTRACT FROM AUTHOR]

Rab proteins (Ras homologous for brain) play an important role in vesicle trafficking. Rab4 and Rab11 are involved in vesicular trafficking to the plasma membrane from early endosomes and recycling endosomes, respectively. Tauroursodeoxycholate (TUDC) and cAMP increase bile formation, in part, by increasing plasma membrane localization of multidrug resistance-associated protein 2 (MRP2). The goal of the present study was to determine the role of these Rab proteins in the trafficking of MRP2 by testing the hypothesis that Rab11 and/or Rab4 facilitate cAMP- and TUDC-induced MRP2 translocation to the plasma membrane. Studies were conducted in HuH-NTCP cells (HuH7 cells stably transfected with human NTCP), which constitutively express MRP2. HuH-NTCP cells were transfected with Rab11-WT and GDP-locked dominant inactive Rab11-GDP or with Rab4-GDP to study the role of Rab11 and Rab4. A biotinylation method and a GTP overlay assay were used to determine plasma membrane MRP2 and activation of Rab proteins (Rab11 and Rab4), respectively. Cyclic AMP and TUDC increased plasma membrane MRP2 and stimulated Rab11 activity. Plasma membrane translocation of MRP2 by cAMP and TUDC was increased and inhibited in cells transfected with Rab11-WT and Rab11-GDP, respectively. Cyclic AMP (previous study) and TUDC increased Rab4 activity. However, cAMP- and TUDC-induced increases in MRP2 were not inhibited by Rab4-GDP. Taken together, these results suggest that Rab11 is involved in cAMP- and TUDCinduced MRP2 translocation to the plasma membrane. [ABSTRACT FROM AUTHOR]