Quantifying Prefibrillar Amyloids in vitro by Using a “Thioflavin‐Like” Spectroscopic Method

In Alzheimer's disease (AD) and other neurodegenerative disorders, proteins accumulate into ordered aggregates, called amyloids. Recent evidence suggests that these structures include both large, insoluble fibrils and smaller, prefibrillar structures, such as dimers, oligomers, and protofibrils. Recently, focus has shifted to the prefibrillar aggregates because they are highly neurotoxic and their levels appear to correlate with cognitive impairment. Thus, there is interest in finding methods for specifically quantifying these structures. One of the classic ways of detecting amyloid formation is through the fluorescence of the benzothiazole dye, thioflavin T (ThT). This reagent has been a “workhorse” of the amyloid field because it is robust and inexpensive. However, one of its limitations is that it does not distinguish between prefibrillar and fibrillar aggregates. We screened a library of 37 indoles for those that selectively change fluorescence in the presence of prefibrillar amyloid‐β (Aβ). From this process, we selected the most promising example, tryptophanol (TROL), to use in a quantitative “thioflavin‐like” assay. Using this probe in combination with electron microscopy, we found that prefibrils are largely depleted during Aβ aggregation in vitro but that they remain present after the apparent saturation of the ThT signal. These results suggest that a combination of TROL and ThT provides greater insight into the process of amyloid formation by Aβ. In addition, we found that TROL also recognizes other amyloid‐prone proteins, including ataxin‐3, amylin, and CsgA. Thus, this assay might be an inexpensive spectroscopic method for quantifying amyloid prefibrils in vitro.     

Hydrogenation of 3,4-epoxy-1-butene over Cu–Pd/SiO2 catalysts prepared by electroless deposition

Electroless deposition has been used to prepare Cu–Pd/SiO₂ bimetallic catalysts wherein initial Cu coverages are limited only to the pre-existing Pd surface. Cu loading on the Pd surface can be systematically varied by modification of deposition kinetic parameters. In this case deposition time was used as the kinetic variable for the preparation of a series of Cu–Pd catalysts. These materials have been characterized using atomic absorption, CO chemisorption, and FT-IR (adsorption of CO), and then evaluated for the hydrogenation of 3,4-epoxy-1-butene, a functionalized olefin having many potential reaction pathways. Catalyst performance and characterization results suggest that Cu is not distributed in a monodisperse manner on the Pd surface, indicating the existence of autocatalytic deposition of Cu on Cu sites. The FT-IR results suggest that although CO adsorption on all sites is suppressed by Cu addition, initial Cu deposition occurs more readily on certain sites. The bimetallic Cu–Pd sites that are formed exhibit unusually high activity for EpB conversion and formation of unsaturated alcohols and aldehydes. This bimetallic effect on catalyst activity and selectivity is best explained, not by the existence of either ligand or ensemble effects, but rather by the bifunctional nature of the Cu–Pd sites present on the surface of these catalysts.     

Curative treatment for pancreatic neoplasms. Radical resection

The available data suggest that lymph node involvement is an important prognostic factor in patients with carcinoma of the head of the pancreas. Lymph node metastases occur in as many as 50% of the cases of even the smallest pancreatic cancers now being diagnosed and resected (i.e., those < 2 cm in diameter). There is some evidence, especially from clinical experience in Japan, that wider lymphatic dissections (i.e., wider than those commonly done with the standard Whipple resection) may prolong survival. Unfortunately, many of the available data around the world are retrospective and are not randomized between the standard and the radical operation. Moreover, the pathologic material has not been staged uniformly according to accepted criteria. Thus the various series are not comparable. Comparisons between series require standardization with respect to stage of disease, pathologic classification, and treatment protocols. Before any modification of the standard pancreaticoduodenectomy is adopted, an appropriately designed study should be performed to test its efficacy. This study would also require a more comprehensive analysis of the pathologic material than is commonly performed today in the United States and Europe.     

Sex-Specific Effects of Plastic Caging in Murine Viral Myocarditis

Background: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers. Methods: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection. Results: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis. Conclusions: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.     

The Impact of Dietary Interventions on the Symptoms of Inflammatory Bowel Disease: A Systematic Review

Diet may be a successful part of the treatment plan for improving outcome in patients with inflammatory bowel disease (IBD). This study aimed to systematically review all published clinical trials evaluating the effects of a regular diet on symptoms of IBD. Three medical databases were searched for clinical trials evaluating an intervention that involved dietary manipulation using a regular diet on adults with IBD whose symptoms were objectively measured before and after the intervention. The most common types of regular diet interventions that we observed in the literature fell into the following three categories: low residue/low fiber diets, exclusion diets, or other specific diets. Of all included studies, the few that were of higher quality and that observed a statistically significant improvement in symptoms in the diet group compared to the control group fell under the exclusion diet group or the other specific diet group. We were able to identify several high quality clinical trials evaluating dietary manipulations on symptoms of IBD. Exclusion diets and the low FODMAP diet are two areas identified in this review that show promise for having therapeutic benefits for patients with IBD.     

Dried plum products as a substitute for phosphate in chicken marinade

In order to address the growing demand for more natural poultry products, alkaline phosphates commonly used in chicken breast meat marinades were replaced with plum ingredients and evaluated. For initial sensory evaluation, 200 consumers of chicken were served a small portion of the chicken breast on a plate and were asked to evaluate the product for overall impression, flavor, and texture on a 9-point hedonic scale with 1 = "dislike extremely" and 9 = "like extremely." Also, a 5-point just-about-right (JAR) scale was used on questions about tenderness, juiciness, overall flavor, and saltiness. Both hedonic and JAR demonstrated that the marinades of plum concentrate and the blend of plum fiber and powder were not distinguishable from the control (P > 0.05). Using two different percentages of fiber/powder blend, two different percentages of concentrate, sodium tripolyphosphate (STPP), and no marinade, measurements were made for marinade per cent pickup, thaw loss, and cook loss. Plum concentrate at 1.1% was most similar to STPP in marinade per cent pickup, thaw loss, drip loss, and cook loss. These results show that plum ingredients can potentially be used as a substitute in standard phosphate marinades. PRACTICAL APPLICATION: Consumers are increasingly demanding more natural foods with less artificial additives. This research presents the results of experiments using dried plum ingredients as a substitute for phosphates commonly used in marinades for chicken. Results indicate that dried plum ingredients may be a suitable substitute for phosphates in marinades.