Keynote Speaker Presentations: 5th Annual UMass Center for Clinical and Translational Research Retreat (video)

This video features the full keynote presentations from the 5th Annual UMass Center for Clinical and Translational Science Research Retreat at the University of Massachusetts Medical School (UMMS) in Worcester, MA, on May 20, 2014. Beginning at 12:40 1st Keynote Speaker: Robert H. Brown, Jr., MD, D.Phil, Chair, Department of Neurology, UMMS. “Lou Gehrig Disease: From Mapping to Medicines” Beginning at 1:22:19 2nd Keynote Speaker: Thomas Grisso, PhD, Director, Law and Psychiatry Program and Professor, Department of Psychiatry, UMMS. Recipient, Chancellor’s Medal for Distinguished Scholarship. “Translational Research in Law and Psychiatry” Also included is a brief introductory presentation with updates about the UMass Center for Clinical and Translational Science by Katherine Luzuriaga, MD, Director, UMCCTS

SEGMENTING NICHE GOAT-MEAT MARKETS

This research report provides an examination of the ratings of an important sensory attribute of chevon (goat meat) with that of beef and pork. Results from an analysis of variance of comparative ratings of the flavor of chevon and that of beef and pork suggest that selected demographic characteristics of U.S. consumers influenced the ratings of chevon'Â’s flavor with that of beef and pork. The findings indicate that Hispanics, blacks, and females should not be treated as homogenous niche markets. The results suggest that there are distinct subdivision preferences within and between these consumer partitions.Agribusiness,

Translation inhibition by rocaglates activates a species-specific cell death program in the emerging fungal pathogen Candida auris

Fungal infections are a major contributor to infectious disease-related deaths worldwide. Recently, global emergence of the fungal pathogen Candida auris has caused considerable concern because most C. auris isolates are resistant to fluconazole, the most commonly administered antifungal, and some isolates are resistant to drugs from all three major antifungal classes. To identify novel agents with bioactivity against C. auris, we screened 2,454 compounds from a diversity-oriented synthesis collection. Of the five hits identified, most shared a common rocaglate core structure and displayed fungicidal activity against C. auris These rocaglate hits inhibited translation in C. auris but not in its pathogenic relative Candida albicans Species specificity was contingent on variation at a single amino acid residue in Tif1, a fungal member of the eukaryotic initiation factor 4A (eIF4A) family of translation initiation factors known to be targeted by rocaglates. Rocaglate-mediated inhibition of translation in C. auris activated a cell death program characterized by loss of mitochondrial membrane potential, increased caspase-like activity, and disrupted vacuolar homeostasis. In a rocaglate-sensitized C. albicans mutant engineered to express translation initiation factor 1 (Tif1) with the variant amino acid that we had identified in C. auris, translation was inhibited but no programmed cell death phenotypes were observed. This surprising finding suggests divergence between these related fungal pathogens in their pathways of cellular responses to translation inhibition. From a therapeutic perspective, the chemical biology that we have uncovered reveals species-specific vulnerability in C. auris and identifies a promising target for development of new, mechanistically distinct antifungals in the battle against this emerging pathogen. IMPORTANCE Emergence of the fungal pathogen Candida auris has ignited intrigue and alarm within the medical community and the public at large. This pathogen is unusually resistant to antifungals, threatening to overwhelm current management options. By screening a library of structurally diverse molecules, we found that C. auris is surprisingly sensitive to translation inhibition by a class of compounds known as rocaglates (also known as flavaglines). Despite the high level of conservation across fungi in their protein synthesis machinery, these compounds inhibited translation initiation and activated a cell death program in C. auris but not in its relative Candida albicans Our findings highlight a surprising divergence across the cell death programs operating in Candida species and underscore the need to understand the specific biology of a pathogen in attempting to develop more-effective treatments against it.Published versio

Three-Dimensional Molecular Modeling of Bovine Caseins

Three-dimensional (3 -D) structures derived from X-ray crystallography are important in elucidating structure- function relationships for many proteins. However, not all food proteins can be crystallized. The casei ns of bovine milk are one class of non-crysta11izable proteins (a, 1-, K-, and /3-). The complete primary and partial secondary structures of these proteins are known, but homologous proteins of known crystallographic structure cannot be found. Therefore , sequence based predictions of secondary structure were made and adjusted to conform with data from Raman and Fourier-transformed infra- red spectroscopy. With this information, 3-D structures for these caseins were built using the Sybyl molecular modeling programs. The K-casein structure contained two anti-parallel P-sheets which are predominately hydrophobic. The a,1-casein structure also contained a hydrophobic domain composed of .B-sheets as well as a hydrophilic domain ; these two are connected by a segment of ex- helix . Both the K- and a,1-caseins represent unrefined models in that they have been manipulated to remove unrealistic bonds but have not been energy-mini mized . Nevertheless the models account for the tendency of these caseins to associate. The .B-casein model appears to follow a divergent structural pattern. When subjected to energy minimization, it yielded a loosely packed structure with an ax.ial ratio of 2 to I, a hydrophobic C-terminal domain , and a hydrophilic N-terminal end. All three casein structures showed good agreement with literature concerning their global biochemical and physico-chemical properties

Archaeological Test Excavations at 41MV57: The Seco Mines Project, Maverick County, Texas

In mid-February, 1977, an archaeological field team from the Center for Archaeological Research, The University of Texas at San Antonio, conducted investigations at prehistoric site 41 MV 57 in Maverick County, Texas. The site is located along a tributary of Seco Creek and is to be modified by the installation of a sewage collection system (the Seco Mines Project)