Intestinal epithelial cell-intrinsic deletion of Setd7 identifies role for developmental pathways in immunity to helminth infection

The intestine is a common site for a variety of pathogenic infections. Helminth infections continue to be major causes of disease worldwide, and are a significant burden on health care systems. Lysine methyltransferases are part of a family of novel attractive targets for drug discovery. SETD7 is a member of the Suppressor of variegation 3-9-Enhancer of zeste-Trithorax (SET) domain-containing family of lysine methyltransferases, and has been shown to methylate and alter the function of a wide variety of proteins in vitro. A few of these putative methylation targets have been shown to be important in resistance against pathogens. We therefore sought to study the role of SETD7 during parasitic infections. We find that Setd7-/- mice display increased resistance to infection with the helminth Trichuris muris but not Heligmosomoides polygyrus bakeri. Resistance to T. muris relies on an appropriate type 2 immune response that in turn prompts intestinal epithelial cells (IECs) to alter differentiation and proliferation kinetics. Here we show that SETD7 does not affect immune cell responses during infection. Instead, we found that IEC-specific deletion of Setd7 renders mice resistant to T. muris by controlling IEC turnover, an important aspect of anti-helminth immune responses. We further show that SETD7 controls IEC turnover by modulating developmental signaling pathways such as Hippo/YAP and Wnt/β-Catenin. We show that the Hippo pathway specifically is relevant during T. muris infection as verteporfin (a YAP inhibitor) treated mice became susceptible to T. muris. We conclude that SETD7 plays an important role in IEC biology during infection

Internal Marketing Perceptions in Intercollegiate Athletics and Their Influence on Organizational Commitment

While scholars have previously focused on the external impact of marketing efforts in college athletics (e.g., Gladden, Irwin, & Sutton, 2001), little research has been done on the internal marketing orientation of collegiate sport properties and its respective impact on college sport. The purpose of this study is to determine the perceptions of internal marketing in college athletics and to examine if those perceptions have an effect on the level of organizational commitment among departmental employees. Survey methodology collected information from 248 athletic department administrators at NCAA FBS and FCS institutions. Results indicate that internal marketing orientation strongly influenced affective commitment to the organization. Further, internal marketing was found to fully mediate the relationship of job function and affective commitment. Finally, theorized moderators of job type, level of competition and gender were not statistically significant. The results support the assertion that an internal marketing orientation can be effectively implemented to foster the development of affective commitment to the organization

Intercollegiate Athletics and Institutional Fundraising: A Meta-Analysis

After nearly 30 years of research, the disparate findings of studies examining the influence of intercollegiate athletics on private, individual giving to higher education institutions have failed to generate generalizable knowledge. The current study examined all available empirical studies conducted between 1976 and 2008 on this topic. Meta-analysis results indicate that intercollegiate athletics does have a small, but statistically significant, effect on giving. Follow-up analysis revealed four significant moderators on the strength of the intercollegiate athletic-private giving relationship: the gift target (i.e., athletic vs. academic programs), the alumni status of the donor, the level of NCAA membership, and whether or not the institution competes in football. Implications of the results and directions for future research are discussed

The Comparative Toxicogenomics Database (CTD).

The Mount Desert Island Biological Laboratory in Salsbury Cove, Maine, USA, is developing the Comparative Toxicogenomics Database (CTD), a community-supported genomic resource devoted to genes and proteins of human toxicologic significance. CTD will be the first publicly available database to a) provide annotated associations among genes, proteins, references, and toxic agents, with a focus on annotating data from aquatic and mammalian organisms; b) include nucleotide and protein sequences from diverse species; c) offer a range of analysis tools for customized comparative studies; and d) provide information to investigators on available molecular reagents. This combination of features will facilitate cross-species comparisons of toxicologically significant genes and proteins. These comparisons will promote understanding of molecular evolution, the significance of conserved sequences, the genetic basis of variable sensitivity to environmental agents, and the complex interactions between the environment and human health. CTD is currently under development, and the planned scope and functions of the database are described herein. The intent of this report is to invite community participation in the development of CTD to ensure that it will be a valuable resource for environmental health, molecular biology, and toxicology research

Dynamical analysis of extreme precipitation in the US northeast based on large-scale meteorological patterns

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.Previous work has identified six large-scale meteorological patterns (LSMPs) of dynamic tropopause height associated with extreme precipitation over the Northeast US, with extreme precipitation defined as the top 1% of daily station precipitation. Here, we examine the three-dimensional structure of the tropopause LSMPs in terms of circulation and factors relevant to precipitation, including moisture, stability, and synoptic mechanisms associated with lifting. Within each pattern, the link between the different factors and extreme precipitation is further investigated by comparing the relative strength of the factors between days with and without the occurrence of extreme precipitation. The six tropopause LSMPs include two ridge patterns, two eastern US troughs, and two troughs centered over the Ohio Valley, with a strong seasonality associated with each pattern. Extreme precipitation in the ridge patterns is associated with both convective mechanisms (instability combined with moisture transport from the Great Lakes and Western Atlantic) and synoptic forcing related to Great Lakes storm tracks and embedded shortwaves. Extreme precipitation associated with eastern US troughs involves intense southerly moisture transport and strong quasi-geostrophic forcing of vertical velocity. Ohio Valley troughs are associated with warm fronts and intense warm conveyor belts that deliver large amounts of moisture ahead of storms, but little direct quasi-geostrophic forcing. Factors that show the largest difference between days with and without extreme precipitation include integrated moisture transport, low-level moisture convergence, warm conveyor belts, and quasi-geostrophic forcing, with the relative importance varying between patterns.National Science FoundationSwiss National Science Foundation (SNSF

Fiber-Flux Diffusion Density for White Matter Tracts Analysis: Application to Mild Anomalies Localization in Contact Sports Players

We present the concept of fiber-flux density for locally quantifying white matter (WM) fiber bundles. By combining scalar diffusivity measures (e.g., fractional anisotropy) with fiber-flux measurements, we define new local descriptors called Fiber-Flux Diffusion Density (FFDD) vectors. Applying each descriptor throughout fiber bundles allows along-tract coupling of a specific diffusion measure with geometrical properties, such as fiber orientation and coherence. A key step in the proposed framework is the construction of an FFDD dissimilarity measure for sub-voxel alignment of fiber bundles, based on the fast marching method (FMM). The obtained aligned WM tract-profiles enable meaningful inter-subject comparisons and group-wise statistical analysis. We demonstrate our method using two different datasets of contact sports players. Along-tract pairwise comparison as well as group-wise analysis, with respect to non-player healthy controls, reveal significant and spatially-consistent FFDD anomalies. Comparing our method with along-tract FA analysis shows improved sensitivity to subtle structural anomalies in football players over standard FA measurements

Multivisceral intestinal transplantation: Surgical pathology

We report the diagnostic surgical pathology of two children who underwent multivisceral abdominal transplantation and survived for 1 month and 6 months. There is little relevant literature, and diagnostic criteria for the various clinical possibilities are not established; this is made more complicated by the simultaneous occurrence of more than one process. We based our interpretations on conventional histology, augmented with immunohistology, including HLA staining that distinguished graft from host cells in situ. In some instances functional analysis of T cells propagated from the same biopsies was available and was used to corroborate morphological interpretations. A wide spectrum of changes was encountered. Graft-versus-host disease, a prime concern before surgery, was not seen. Rejection was severe in 1 patient, not present in the other, and both had evidence of lymphoproliferative disease, which was related to Epstein-Barr virus. Bacterial translocation through the gut wall was also a feature in both children. This paper documents and illustrates the various diagnostic possibilities.. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Moral reasoning and homosexuality: the acceptability of arguments about lesbian and gay issues

In the political arena, lesbian and gay issues have typically been contested on grounds of human rights, but with variable success. Using a moral developmental framework, the purpose of this study was to explore preferences for different types of moral arguments when thinking about moral dilemmas around lesbian and gay issues. The analysis presented here comprised data collected from 545 students at UK universities, who completed a questionnaire, part of which comprised a moral dilemma task. Findings of the study showed that respondents do not apply moral reasoning consistently, and do not (clearly) favour human rights reasoning when thinking about lesbian and gay issues. Respondents tended to favour reasoning supporting existing social structures and frameworks, therefore this study highlights the importance of structural change in effecting widespread attitude change in relation to lesbian and gay rights issues. The implications of the findings for moral education are also discussed.</p