An Expanded Set of Fluorogenic Sulfatase Activity Probes

Fluorogenic probes that are activated by an enzymatic transformation are ideally suited for profiling enzyme activities in biological systems. Here, we describe two fluorogenic enzyme probes, 3‐O‐methylfluorescein‐sulfate and resorufin‐sulfate, that can be used to detect sulfatases in mycobacterial lysates. Both probes were validated with a set of commercial sulfatases and used to reveal species‐specific sulfatase banding patterns in a gel‐resolved assay of mycobacterial lysates. The fluorogenic probes described here are suitable for various assays and provide a starting point for creating new sulfatase probes with improved selectivity for mycobacterial sulfatases.     

Small‐Molecule Inhibitors of AF6 PDZ‐Mediated Protein–Protein Interactions

PDZ (PSD‐95, Dlg, ZO‐1) domains are ubiquitous interaction modules that are involved in many cellular signal transduction pathways. Interference with PDZ‐mediated protein–protein interactions has important implications in disease‐related signaling processes. For this reason, PDZ domains have gained attention as potential targets for inhibitor design and, in the long run, drug development. Herein we report the development of small molecules to probe the function of the PDZ domain from human AF6 (ALL1‐fused gene from chromosome 6), which is an essential component of cell–cell junctions. These compounds bind to AF6 PDZ with substantially higher affinity than the peptide (Ile‐Gln‐Ser‐Val‐Glu‐Val) derived from its natural ligand, EphB2. In intact cells, the compounds inhibit the AF6–Bcr interaction and interfere with epidermal growth factor (EGF)‐dependent signaling.     

Total phenolic content, consumer acceptance, and instrumental analysis of bread made with grape seed flour

Grape seed flour (GSF) from grape pomace, a waste product generated during winemaking, was explored for use in bread production due to its potential health benefits. This study evaluated the consumer acceptance and physical properties of bread, including total phenolic content (TPC), made with varying levels of GSF. Dough and breads were prepared using different levels of replacement of hard red spring wheat flour (HRS) with GSF (0 to 10 g GSF/100 g HRS) and stored for 0, 2, or 6 wk at -20 °C. Replacement of 10 g GSF/100 g HRS increased the bread TPC from 0.064 mg tannic acid/g dry weight to 4.25 mg tannic acid/g dry weight. Consumer acceptance and instrumental analyses were used to investigate changes in sensory and texture properties due to GSF replacement. Replacement above 5 g GSF/100 g HRS decreased the loaf brightness and volume, with an increase in the bread hardness and porosity. Generally, breads containing ≥ 7.5 g GSF/100 g HRS were characterized by lower consumer acceptance. A reduction in overall and bitterness acceptance was observed in bread at 10 g GSF/100 g HRS, with decreased acceptance of astringency and sweetness at 7.5 and 10 g GSF/100 g HRS. Based on these results, the replacement of 5 g GSF/100 g HRS is recommended for the production of fortified breads with acceptable physical and sensory properties and high TPC activity compared to refined bread. PRACTICAL APPLICATIONS: This study shows that grape seed flour (GSF) can be used to replace hard red spring wheat flour (HRS) in bread production, with moderate impact on the physical and sensory properties of the bread. Replacement of up to 10 g GSF/100 g HRS significantly decreased overall consumer acceptance of the bread, with lower consumer acceptance of sweetness and astringency at 7.5 and 10 g GSF/100 g HRS. Thus, a replacement value of 5 g GSF/100 g HRS is recommended for the production of fortified breads.     

A physics informed emulator for laser-driven radiating shock simulations

This work discusses the uncertainty quantification aspect of quantification of margin and uncertainty (QMU) in the context of two linked computer codes. Specifically, we present a physics based reduction technique to deal with functional data from the first code and then develop an emulator for this reduced data. Our particular application deals with conditions created by laser deposition in a radiating shock experiment modeled using the Lagrangian, radiation-hydrodynamics code Hyades. Our goal is to construct an emulator and perform a sensitivity analysis of the functional output from Hyades to be used as an initial condition for a three-dimensional code that will compute the evolution of the radiating shock at later times. Initial attempts at purely statistical data reduction techniques, were not successful at reducing the number of parameters required to describe the Hyades output. We decided on an alternate approach using physical arguments to decide what features/locations of the output were relevant (e.g., the location of the shock front or the location of the maximum pressure) and then used a piecewise linear fit between these locations. This reduced the number of outputs needed from the emulator to 40, down from the O(1000) points in the Hyades output. Then, using Bayesian MARS and Gaussian process regression, we were able to build emulators for Hyades and study sensitivities to input parameters.     

Psychological services in educational settings to persons with mental retardation.

Reviews the 6 principles of Public Law 94-142 (the Education for All Handicapped Children Act)—including nondiscriminatory evaluation, the least restrictive environment, and individualized education—and discusses ways psychologists may be able to further the achievement of its effectiveness. Mental retardation psychologists provide an array of services, including prevention, consultation, training, education, supervision, administration, research, and consultation on individualized educational plans. Other potential areas for intervention include development of psychometric measures, social ecological assessment, and vocational education. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Letter from Heerleen: A matter of mutual objectives

E.A.C.I.'s corporate liaison sees co-operation and communication amongst members as one way in which to realize mutual objectives. Exploring these objectives is one of the points on the agenda this autumn in the Association's first corporate Podium.     

Use of the Mental Health Inventory with adolescents: A secondary analysis of the Rand Health Insurance Study.

Few instruments exist for the assessment of adolescent mental health. In order to examine the appropriateness of the Mental Health Inventory (MHI) for use with adolescents, secondary analyses were conducted of the large subsample (n?=?953) of adolescents who participated in the community-based Rand Health Insurance Study. The reliability and readability of the MHI were confirmed. Subscales reflecting Psychological Well-Being and Psychological Distress were derived. The MHI, with its adolescent norms, is recommended for the assessment of adolescent mental health, particularly in studies in which comparison to a nonpsychiatric, normative adolescent population is indicated. (PsycINFO Database Record (c) 2011 APA, all rights reserved)