Blockade of adenosine A2B receptors ameliorates murine colitis

Background and purpose: The adenosine 2B (A2B) receptor is the predominant adenosine receptor expressed in the colon. Acting through the A2B receptor, adenosine mediates chloride secretion, as well as fibronectin and interleukin (IL)-6 synthesis and secretion in intestinal epithelial cells. A2B receptor mRNA and protein expression are increased during human and murine colitis. However, the effect of the A2B receptor in the activation of the intestinal inflammatory response is not known. In this study, we examined the effect of A2B receptor antagonism on murine colitis. Experimental approach: Dextran sodium sulphate (DSS)-treated mice and piroxicam-treated IL-10/ mice were used as animal models of colitis. The A2B receptor-selective antagonist, ATL-801, was given in the diet. Key results: Mice fed ATL-801 along with DSS showed a significantly lower extent and severity of colitis than mice treated with DSS alone, as shown by reduced clinical symptoms, histological scores, IL-6 levels and proliferation indices. The administration of ATL-801 prevented weight loss, suppressed the inflammatory infiltrate into colonic mucosa and decreased epithelial hyperplasia in piroxicam-treated IL-10/ mice. IL-6 and keratinocyte-derived chemokine (KC) concentrations in the supernatants of colonic organ cultures from colitic mice were significantly reduced by ATL-801 administration. Conclusions and implications: Taken together, these data demonstrate that the intestinal epithelial A2B receptor is an important mediator of pro-inflammatory responses in the intestine and that A2B receptor blockade may be an effectiv

Facilitating Learning in Large Lecture Classes: Testing the “Teaching Team” Approach to Peer Learning

We tested the effect of voluntary peer-facilitated study groups on student learning in large introductory biology lecture classes. The peer facilitators (preceptors) were trained as part of a Teaching Team (faculty, graduate assistants, and preceptors) by faculty and Learning Center staff. Each preceptor offered one weekly study group to all students in the class. All individual study groups were similar in that they applied active-learning strategies to the class material, but they differed in the actual topics or questions discussed, which were chosen by the individual study groups. Study group participation was correlated with reduced failing grades and course dropout rates in both semesters, and participants scored better on the final exam and earned higher course grades than nonparticipants. In the spring semester the higher scores were clearly due to a significant study group effect beyond ability (grade point average). In contrast, the fall study groups had a small but nonsignificant effect after accounting for student ability. We discuss the differences between the two semesters and offer suggestions on how to implement teaching teams to optimize learning outcomes, including student feedback on study groups

The Effects of Sex-Role Attitudes and Group Composition on Men and Women in Groups

The dual impact of group gender composition and sex-role attitudes on self-perceptions and social behavior was explored. Androgynous and stereotyped men and women were placed in groups of skewed sex composition. Subjects\u27 self-descriptions of masculine attributes shifted significantly in the group environment. In some instances, sex role-stereotyped subjects responded most stereotypically when their gender was in the minority in the group. Differences between men and women and between androgynous and stereotyped subjects in sex role-related preferences for group roles and discussion topics were also found

Autism Spectrum Disorders in Gender Dysphoric Children and Adolescents

Only case reports have described the co-occurrence of gender identity disorder (GID) and autism spectrum disorders (ASD). This study examined this co-occurrence using a systematic approach. Children and adolescents (115 boys and 89 girls, mean age 10.8, SD = 3.58) referred to a gender identity clinic received a standardized assessment during which a GID diagnosis was made and ASD suspected cases were identified. The Dutch version of the Diagnostic Interview for Social and Communication Disorders (10th rev., DISCO-10) was administered to ascertain ASD classifications. The incidence of ASD in this sample of children and adolescents was 7.8% (n = 16). Clinicians should be aware of co-occurring ASD and GID and the challenges it generates in clinical management

Chicken CRTAM Binds Nectin-Like 2 Ligand and Is Upregulated on CD8⁺ αβ and γδ T Lymphocytes with Different Kinetics

During a search for immunomodulatory receptors in the chicken genome, we identified a previously cloned chicken sequence as CRTAM homologue by its overall identity and several conserved sequence features. For further characterization, we generated a CRTAM specific mab. No staining was detectable in freshly isolated cell preparations from thymus, bursa, caecal tonsils, spleen, blood and intestine. Activation of splenocytes with recombinant IL-2 increased rapid CRTAM expression within a 2 h period on about 30% of the cells. These CRTAM+ cells were identified as CD8+ γδ T lymphocytes. In contrast, CRTAM expression could not be stimulated on PBL with IL-2, even within a 48 h stimulation period. As a second means of activation, T cell receptor (TCR) crosslinking using an anti-αβ-TCR induced CRTAM on both PBL and splenocytes. While CRTAM expression was again rapidly upregulated on splenocytes within 2 h, it took 48 h to reach maximum levels of CRTAM expression in PBL. Strikingly, albeit the stimulation of splenocytes was performed with anti-αβ-TCR, CRTAM expression after 2 h was mainly restricted to CD8+ γδ T lymphocytes, however, the longer anti-TCR stimulation of peripheral blood lymphocytes (PBL) resulted in CRTAM expression on αβ T lymphocytes. In order to characterize the potential ligand we cloned and expressed chicken Necl-2, a member of the nectin and nectin-like family which is highly homologous to its mammalian counterpart. Three independent assays including a reporter assay, staining with a CRTAM-Ig fusion protein and a cell conjugate assay confirmed the interaction of CRTAM with Necl-2 which could also be blocked by a soluble CRTAM-Ig fusion protein or a CRTAM specific mab. These results suggest that chicken CRTAM represents an early activation antigen on CD8+ T cells which binds to Necl-2 and is upregulated with distinct kinetics on αβ versus γδ T lymphocytes