Dreams

https://digitalcommons.library.umaine.edu/mmb-vp/4188/thumbnail.jp

In Twilight Town

https://digitalcommons.library.umaine.edu/mmb-vp/3628/thumbnail.jp

Darby And Joan

https://digitalcommons.library.umaine.edu/mmb-vp/1270/thumbnail.jp

I Want A Girl From Home Sweet Home

https://digitalcommons.library.umaine.edu/mmb-vp/1702/thumbnail.jp

Comparative analysis of homology models of the Ah receptor ligand binding domain: Verification of structure-function predictions by site-directed mutagenesis of a nonfunctional receptor

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates the biological and toxic effects of a wide variety of structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While significant interspecies differences in AHR ligand binding specificity, selectivity, and response have been observed, the structural determinants responsible for those differences have not been determined, and homology models of the AHR ligand-binding domain (LBD) are available for only a few species. Here we describe the development and comparative analysis of homology models of the LBD of 16 AHRs from 12 mammalian and nonmammalian species and identify the specific residues contained within their ligand binding cavities. The ligand-binding cavity of the fish AHR exhibits differences from those of mammalian and avian AHRs, suggesting a slightly different TCDD binding mode. Comparison of the internal cavity in the LBD model of zebrafish (zf) AHR2, which binds TCDD with high affinity, to that of zfAHR1a, which does not bind TCDD, revealed that the latter has a dramatically shortened binding cavity due to the side chains of three residues (Tyr296, Thr386, and His388) that reduce the amount of internal space available to TCDD. Mutagenesis of two of these residues in zfAHR1a to those present in zfAHR2 (Y296H and T386A) restored the ability of zfAHR1a to bind TCDD and to exhibit TCDD-dependent binding to DNA. These results demonstrate the importance of these two amino acids and highlight the predictive potential of comparative analysis of homology models from diverse species. The availability of these AHR LBD homology models will facilitate in-depth comparative studies of AHR ligand binding and ligand-dependent AHR activation and provide a novel avenue for examining species-specific differences in AHR responsiveness. © 2013 American Chemical Society

Location Preferences of Family Firms: Strategic Decision Making or “Home Sweet Home”?

Selecting a business location is among the most important strategic decisions for family firms. Yet the separate demands of the family and the business often prove difficult to balance. A comparison of location preferences in family and nonfamily firms provides insight into the family influence on strategic decision making.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67069/2/10_1111_j_1741-6248_1992_00271_x.pd

Murine Hepatitis Virus Replicase Protein nsp10 Is a Critical Regulator of Viral RNA Synthesis

Coronavirus replication requires proteolytic processing of the large polyprotein encoded by ORF1a/ab into putative functional intermediates and eventually ∼15 mature proteins. The C-terminal ORF1a protein nsp10 colocalizes with viral replication complexes, but its role in transcription/replication is not well defined. To investigate the role of nsp10 in coronavirus transcription/replication, alanine replacements were engineered into a murine hepatitis virus (MHV) infectious clone in place of conserved residues in predicted functional domains or charged amino acid pairs/triplets, and rescued viruses were analyzed for mutant phenotypes. Of the 16 engineered clones, 5 viable viruses were rescued, 3 mutant viruses generated no cytopathic effect but were competent to synthesize viral subgenomic RNAs, and 8 were not viable. All viable mutants showed reductions in growth kinetics and overall viral RNA synthesis, implicating nsp10 as being a cofactor in positive- or negative-strand synthesis. Viable mutant nsp10-E2 was compromised in its ability to process the nascent polyprotein, as processing intermediates were detected in cells infected with this virus that were not detectable in wild-type infections. Mapping the mutations onto the crystal structure of severe acute respiratory syndrome virus nsp10 identified a central core resistant to mutation. Mutations targeting residues in or near either zinc-binding finger generated nonviable phenotypes, demonstrating that both domains are essential to nsp10 function and MHV replication. All mutations resulting in viable phenotypes mapped to loops outside the central core and were characterized by a global decrease in RNA synthesis. These results demonstrate that nsp10 is a critical regulator of coronavirus RNA synthesis and may play an important role in polyprotein processing

Nitroglycerin for treatment of retained placenta: a randomized, placebo-controlled, multicentre double blind trial in the UK

Funding: The GOT-IT trial was funded by the UK National Institute for Health Research (NIHR; https://www.nihr.ac.uk) Health Technology Assessment (HTA) Program in response to a specific commissioned grant call (Project number 12/29/01). The following co-authors were grant holders: FCD, GM, MP, JB, GS, JL, JN and JEN. The funders played no role in the study design, data collection, analysis, decision to publish or preparation of the manuscript. This work was undertaken in the MRC Centre for Reproductive Health which is funded by MRC Centre grant (MRC G1002033). Data Availability: The GOT-IT Trial contains a centrally-managed cross centre dataset which is available, upon request, from the Digital Curation Centre within the University of Edinburgh. Data requests can be made at [email protected] reviewedPublisher PD

Evaluation of Serologic and Antigenic Relationships Between Middle Eastern Respiratory Syndrome Coronavirus and Other Coronaviruses to Develop Vaccine Platforms for the Rapid Response to Emerging Coronaviruses

Background. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs