Cue reactivity in cannabis-dependent adolescents.

The authors measured event-related potentials with a craving manipulation to investigate the neural correlates of drug cue reactivity in 13 adolescents who are cannabis dependent (CD; ages 14–17). The P300 responses to marijuana (MJ) pictures (MJ-P300) and control pictures (C-P300) were assessed after handling neutral objects and again after handling MJ paraphernalia (MJP). Self-reported drug craving and heart rates also were measured. MJ-P300 were larger than C-P300 (p p = .002 and p = .003, respectively), with no association between the magnitude of craving and MJ-P300. Heart rates were not affected by handling MJP. The results showed that adolescents who are CD have an attentional bias to MJ stimuli that increases after handling marijuana paraphernalia. Generally, the results are consistent with what has been reported for adult heavy chronic cannabis smokers, although there were some differences that require further investigation. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Ingredients and pH are Key to Clear Beverages that Contain Whey Protein

ABSTRACT:  A challenge of shelf stable beverages that contain whey protein is that a small portion of protein can be denatured and aggregated during thermal processing, resulting in a turbid solution or white precipitate that consumers perceive as a defect. In this study, 3 approaches were taken to reduce turbidity in heat-treated beverages that contain whey protein: (1) centrifugation to remove insoluble protein aggregates, (2) addition of ingredients, and (3) alteration of pH in the range from 3.0 to 4.0. At pH 3.6 and below, all samples were essentially clear both before and after heating for all ingredients. At a pH of 3.8 and above, ingredient selection was crucial to solution clarity after heat treatment. At a pH of 4.0, addition of salts at both 10 and 50 mM increased the turbidity significantly compared to the control, which contained only whey protein in water. Neither addition of sugars at 25, 50, and 100 g/L, nor addition of sugar alcohols at 25 g/L significantly affected turbidity after heat treatment compared to the control. However, sugar alcohols added at 50 or 100 g/L significantly reduced turbidity after heat treatment compared to the control. Removal of insoluble protein aggregates by centrifugation prior to heat treatment resulted in a statistically significant decrease in turbidity after heat treatment. Understanding these results at the molecular level will assist food scientists in selecting processing treatments, ingredients, and pH in the development of shelf stable clear beverages that contain whey protein.     

Targeting Insulin-Degrading Enzyme in Insulin Clearance

Hepatic insulin clearance, a physiological process that in response to nutritional cues clears ~50–80% of circulating insulin, is emerging as an important factor in our understanding of the pathogenesis of type 2 diabetes mellitus (T2DM). Insulin-degrading enzyme (IDE) is a highly conserved Zn²⁺-metalloprotease that degrades insulin and several other intermediate-size peptides. Both, insulin clearance and IDE activity are reduced in diabetic patients, albeit the cause-effect relationship in humans remains unproven. Because historically IDE has been proposed as the main enzyme involved in insulin degradation, efforts in the development of IDE inhibitors as therapeutics in diabetic patients has attracted attention during the last decades. In this review, we retrace the path from Mirsky’s seminal discovery of IDE to the present, highlighting the pros and cons of the development of IDE inhibitors as a pharmacological approach to treating diabetic patients.     

Reconfigurable Dual Peptide Tethered Polymer System Offers a Synergistic Solution for Next Generation Dental Adhesives

Resin-based composite materials have been widely used in restorative dental materials due to their aesthetic, mechanical, and physical properties. However, they still encounter clinical shortcomings mainly due to recurrent decay that develops at the composite-tooth interface. The low-viscosity adhesive that bonds the composite to the tooth is intended to seal this interface, but the adhesive seal is inherently defective and readily damaged by acids, enzymes, and oral fluids. Bacteria infiltrate the resulting gaps at the composite-tooth interface and bacterial by-products demineralize the tooth and erode the adhesive. These activities lead to wider and deeper gaps that provide an ideal environment for bacteria to proliferate. This complex degradation process mediated by several biological and environmental factors damages the tooth, destroys the adhesive seal, and ultimately, leads to failure of the composite restoration. This paper describes a co-tethered dual peptide-polymer system to address composite-tooth interface vulnerability. The adhesive system incorporates an antimicrobial peptide to inhibit bacterial attack and a hydroxyapatite-binding peptide to promote remineralization of damaged tooth structure. A designer spacer sequence was incorporated into each peptide sequence to not only provide a conjugation site for methacrylate (MA) monomer but also to retain active peptide conformations and enhance the display of the peptides in the material. The resulting MA-antimicrobial peptides and MA-remineralization peptides were copolymerized into dental adhesives formulations. The results on the adhesive system composed of co-tethered peptides demonstrated both strong metabolic inhibition of S. mutans and localized calcium phosphate remineralization. Overall, the result offers a reconfigurable and tunable peptide-polymer hybrid system as next-generation adhesives to address composite-tooth interface vulnerability.     

What Is the Role of HLA-I on Cancer Derived Extracellular Vesicles? Defining the Challenges in Characterisation and Potential Uses of This Ligandome

The Human Leukocyte Antigen class I (HLA-I) system is an essential part of the immune system that is fundamental to the successful activation of cytotoxic lymphocytes, and an effective subsequent immune attack against both pathogen-infected and cancer cells. The importance of cytotoxic T cell activity and ability to detect foreign cancer-related antigenic peptides has recently been highlighted by the successful application of monoclonal antibody-based checkpoint inhibitors as novel immune therapies. Thus, there is an increased interest in fully characterising the repertoire of peptides that are being presented to cytotoxic CD8+ T cells by cancer cells. However, HLA-I is also known to be present on the surface of extracellular vesicles, which are released by most if not all cancer cells. Whilst the peptide ligandome presented by cell surface HLA class I molecules on cancer cells has been studied extensively, the ligandome of extracellular vesicles remains relatively poorly defined. Here, we will describe the current understanding of the HLA-I peptide ligandome and its role on cancer-derived extracellular vesicles, and evaluate the aspects of the system that have the potential to advance immune-based therapeutic approaches for the effective treatment of cancer.     

Network behavior of thermosetting polyimide/multiwalled carbon nanotube composites

In previous published research, network formation has been used to understand morphology and properties in polymer nanocomposites containing carbon nanotubes (CNTs) through measurements of rheological and electrical percolation thresholds, largely in thermoplastic matrices. In this research, these tools are explored as a means to understand network transport mechanisms and changes in CNT dispersion during curing in a thermosetting matrix. Specifically, rheological and electrical measurements were performed on the uncured nanocomposites, and electrical measurements were performed on the cured nanocomposites. The resulting data were applied to a percolation model. The results showed that the uncured resin played a limited role in mediating rheological transport and that little CNT aggregation occurred during curing. The results of this initial work suggest that such a combination of techniques is applicable to understanding dispersion changes resulting from curing and provides complementary insight to that provided by electron microscopy imaging of the same phenomenon.     

Host Plant Suitability in a Specialist Herbivore, <Emphasis Type="Italic">Euphydryas anicia</Emphasis> (Nymphalidae): Preference,Performance and Sequestration

The checkerspot butterfly, Euphydryas anicia (Nymphalidae), specializes on plants containing iridoid glycosides and has the ability to sequester these compounds from its host plants. This study investigated larval preference, performance, and sequestration of iridoid glycosides in a population of E. anicia at Crescent Meadows, Colorado, USA. Although previous studies showed that other populations in Colorado use the host plant, Castilleja integra (Orobanchaceae), we found no evidence for E. anicia ovipositing or feeding on C. integra at Crescent Meadows. Though C. integra and another host plant, Penstemon glaber (Plantaginaceae), occur at Crescent Meadows, the primary host plant used was P. glaber. To determine why C. integra was not being used at the Crescent Meadows site, we first examined the host plant preference of naïve larvae between P. glaber and C. integra. Then we assessed the growth and survivorship of larvae reared on each plant species. Finally, we quantified the iridoid glycoside concentrations of the two plant species and diapausing caterpillars reared on each host plant. Our results showed that E. anicia larvae prefer P. glaber. Also, larvae survive and grow better when reared on P. glaber than on C. integra. Castilleja integra was found to contain two primary iridoid glycosides, macfadienoside and catalpol, and larvae reared on this plant sequestered both compounds; whereas P. glaber contained only catalpol and larvae reared on this species sequestered catalpol. Thus, although larvae are able to use C. integra in the laboratory, the drivers behind the lack of use at the Crescent Meadows site remain unclear.     

Improving the Compostability of Natural Fiber-Reinforced Thermoset Composites with a Tertiary Oil Phase

Although fiberglass-reinforced composites play important roles in many industrial applications, the non-biodegradability of the fibers poses some environmental concerns. In this study, bamboo, cotton and hemp are used as natural reinforcing fibers for polyester and epoxy composites. A tertiary oil phase is also added to the matrix and its effect on material biodegradability is characterized. Results show that material biodegradability is increased up to 100% under controlled composting conditions with oil addition. Polyester biodegrades more effectively than epoxy under both macroscopic and microscopic mechanisms. Mechanical strengths of the polyester composites are also found to correlate strongly with material biodegradability.     

Hydroxypyridinethione Inhibitors of Human Insulin-Degrading Enzyme

Insulin-degrading enzyme (IDE) is a human mononuclear Zn²⁺-dependent metalloenzyme that is widely regarded as the primary peptidase responsible for insulin degradation. Despite its name, IDE is also critically involved in the hydrolysis of several other disparate peptide hormones, including glucagon, amylin, and the amyloid β-protein. As such, the study of IDE inhibition is highly relevant to deciphering the role of IDE in conditions such as type-2 diabetes mellitus and Alzheimer disease. There have been few reported IDE inhibitors, and of these, inhibitors that directly target the active-site Zn²⁺ ion have yet to be fully explored. In an effort to discover new, zinc-targeting inhibitors of IDE, a library of ∼350 metal-binding pharmacophores was screened against IDE, resulting in the identification of 1-hydroxypyridine-2-thione (1,2-HOPTO) as an effective Zn²⁺-binding scaffold. Screening a focused library of HOPTO compounds identified 3-sulfonamide derivatives of 1,2-HOPTO as inhibitors of IDE (K_i values of ∼50 μM). Further structure-activity relationship studies yielded several thiophene-sulfonamide HOPTO derivatives with good, broad-spectrum activity against IDE that have the potential to be useful pharmacological tools for future studies of IDE.