Estrogen Receptor-α in the Bed Nucleus of the Stria Terminalis Regulates Social Affiliation in Male Prairie Voles (Microtus ochrogaster)

Estrogen receptor alpha (ERα) typically masculinizes male behavior, while low levels of ERα in the medial amygdala (MeA) and the bed nucleus of the stria terminalis (BST) are associated with high levels of male prosocial behavior. In the males of the highly social prairie vole (Microtus ochrogaster), increasing ERα in the MeA inhibited the expression of spontaneous alloparental behavior and produced a preference for novel females. To test for the effects of increased ERα in the BST, a viral vector was used to enhance ERα expression in the BST of adult male prairie voles. Following treatment, adult males were tested for alloparental behavior with 1–3-day-old pups, and for heterosexual social preference and affiliation. Treatment did not affect alloparental behavior as 73% of ERα-BST males and 62.5% of control males were alloparental. Increasing ERα in the BST affected heterosexual affiliation, with ERα-BST males spending significantly less total time in side-by-side contact with females relative to time spent with control males. ERα-BST males did not show a preference for either the familiar or novel female. These findings differed significantly from those reported in ERα-MeA enhanced males, where ERα inhibited alloparental behavior and produced a preference for a novel female. The findings from this study suggest two things: first, that increased ERα in the BST decreases social affiliation and second, that altering ERα in different regions of the social neural circuit differentially impacts the expression of social behavior

Vertical Integration in the Pediatrics Clerkship: A Case Study

Since the end of the twentieth century, medical educators continue to review and call for changes that will improve how medical students apply their knowledge of basic sciences to the clinical management of their patients. The traditional 2 + 2 curriculum, where basic sciences are taught during the first two years and were followed by clinical clerkships, was challenged with calls to move towards a Z-shaped integrated curriculum, a model which presents bio-medical sciences and clinical cases in parallel or in connection with one another. Faculty at the Frank H. Netter MD School of Medicine developed a vertical integration didactic session that presented an eight-year-old child with an acute asthmatic episode. After a brief introduction, clinical and pre-clinical faculty who teach in Years 1–3 and social work faculty met with medical students placed in small groups to discuss their pertinent field; faculty members rotated among the groups. At the end of the session, the students provided feedback and comments for the continuous quality improvement of the session. The session has been taught four times thus far. A majority of the students expressed satisfaction with the opportunity to review basic science concepts during the clerkship and apply these concepts to develop clinical management skills. Students were also excited to discuss social determinants and the effects of a pediatric chronic illness on the whole family. Combining a review of basic and social science concepts with clinical management, with faculty from pre-clinical and clinical years, was enjoyed by our students, who felt this educational approach expanded their ability to better manage clinical problems. While our case is in pediatrics, we believe the method can be applied to other specialties

High-resolution genetic mapping of mammalian motor activity levels in mice.

Contains fulltext : 80477.pdf (publisher's version ) (Closed access)The generation of motor activity levels is under tight neural control to execute essential behaviors, such as movement toward food or for social interaction. To identify novel neurobiological mechanisms underlying motor activity levels, we studied a panel of chromosome substitution (CS) strains derived from mice with high (C57BL/6J strain) or low motor activity levels (A/J strain) using automated home cage behavioral registration. In this study, we genetically mapped the expression of baseline motor activity levels (horizontal distance moved) to mouse chromosome 1. Further genetic mapping of this trait revealed an 8.3-Mb quantitative trait locus (QTL) interval. This locus is distinct from the QTL interval for open-field anxiety-related motor behavior on this chromosome. By data mining, an existing phenotypic and genotypic data set of 2445 genetically heterogeneous mice (http://gscan.well.ox.ac.uk/), we confirmed linkage to the peak marker at 79 970 253 bp and refined the QTL to a 312-kb interval containing a single gene (A830043J08Rik). Sequence analysis showed a nucleotide deletion in the 3' untranslated region of the Riken gene. Genome-wide microarray gene expression profiling in brains of discordant F(2) individuals from CS strain 1 showed a significant upregulation of Epha4 in low-active F(2) individuals. Inclusion of a genetic marker for Epha4 confirmed that this gene is located outside of the QTL interval. Both Epha4 and A830043J08Rik are expressed in brain motor circuits, and similar to Epha4 mutants, we found linkage between reduced motor neurons number and A/J chromosome 1. Our findings provide a novel QTL and a potential downstream target underlying motor circuitry development and the expression of physical activity levels

Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation

Somatic loss-of-function mutations in the ten-eleven translocation 2 ( TET2) gene occur in a significant proportion of patients with myeloid malignancies. Although there are extensive genetic data implicating TET2 mutations in myeloid transformation, the consequences of Tet2 loss in hematopoietic development have not been delineated. We report here an animal model of conditional Tet2 loss in the hematopoietic compartment that leads to increased stem cell self-renewal in vivo as assessed by competitive transplant assays. Tet2 loss leads to a progressive enlargement of the hematopoietic stem cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis, and extramedullary hematopoiesis. In addition, Tet2 +/− mice also displayed increased stem cell self-renewal and extramedullary hematopoiesis, suggesting that Tet2 haploinsufficiency contributes to hematopoietic transformation in vivo. ► Tet2-expression silencing leads to increased self-renewal ability ► Tet2 deletion leads to progressive defects in hematopoiesis ► Tet2-deficient hematopoietic stem cells show increased repopulating ability ► Tet2-deficient animals develop CMML-like diseas