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We report the synthesis of new examples of the 1,4-dihydropyrrolo[3,4-b]indol-3(2H)-one ring system via Fischer indolization between the appropriate phenylhydrazines and pyrrolidine-2,3-diones. Lithiation at the C-1 position with lithium diisopropylamide following by quenching with iodomethane affords 1-methyl-1,4-dihydropyrrolo[3,4-b]indol-3(2H)-ones in excellent yield. [ABSTRACT FROM AUTHOR]

Protein aggregation causes a wide range of neurodegenerative diseases. Targeting and removing aggregates, but not the functional protein, is a considerable therapeutic challenge. Here, we describe a therapeutic strategy called "RING-Bait," which employs an aggregating protein sequence combined with an E3 ubiquitin ligase. RING-Bait is recruited into aggregates, whereupon clustering dimerizes the RING domain and activates its E3 function, resulting in the degradation of the aggregate complex. We exemplify this concept by demonstrating the specific degradation of tau aggregates while sparing soluble tau. Unlike immunotherapy, RING-Bait is effective against both seeded and cell-autonomous aggregation. RING-Bait removed tau aggregates seeded from Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) brain extracts and was also effective in primary neurons. We used a brain-penetrant adeno-associated virus (AAV) to treat P301S tau transgenic mice, reducing tau pathology and improving motor function. A RING-Bait strategy could be applied to other neurodegenerative proteinopathies by replacing the Bait sequence to match the target aggregate., Competing Interests: Declaration of interests L.V.C.M., G.P., W.A.M., and L.C.J. are listed as inventors on a patent containing data published in this paper., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Zygosaccharomyces parabailii ( Z. parabailii ) causes spoilage in salad dressings due to its tolerance to osmotic pressure. The objective of this study was to determine the effect of organic acids and storage temperatures (4, 10, and 25 °C) on Z. parabailii growth and salad dressing mechanical properties. Acetic, lactic, and gluconic acids were used alone and in combination to acidify salad dressing. Z. parabailii -challenged formulations containing acetic acid alone tended to have lower counts of Z. parabailii when compared to Z. parabailii -challenged formulations containing other acid combinations. Overall, storage temperature had the most impact on Z. parabailii growth over a 45-day storage. Acidulant type and combination impacted salad dressing mechanical properties. During the 45-day storage period, all formulations showed increased viscosity, a Herschel-Bulkley viscosity profile, and elastic-dominant viscoelastic behavior. The degree of change in rheological behaviors over time was dependent on the type of acid used in the formulation., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05459-4., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest/no competing interests., (© The Author(s) 2022.)

School settings can influence child health, including physical activity and diet, through the promotion of high-quality wellness policies. Many studies have analyzed the quality of school wellness policies, but evidence is lacking regarding the dissemination of the policy evaluation results to school districts. This study describes the process the Wisconsin Health Atlas followed to disseminate tailored school wellness policy data reports and interactive dashboards to school districts throughout the state and the results of the statewide dissemination efforts. Prioritizing the translation of research to practice, the process included collaborating with key stakeholders and partners to provide formative feedback on the dissemination activities. The electronic and hard copy reports were disseminated to 232 districts through email and U.S. mail. Each district received a tailored report featuring an executive summary, local data for action, personalized policy recommendations, best practices, and a unique code to enter into interactive data dashboards to explore additional local, regional, and state-level data. In the utilization follow-up survey (20.3% response rate), respondents indicated that the report will help their district to improve the quality of their school wellness policy. Additionally, respondents who had used the report specified they used the data to identify areas for policy improvement and to support their triennial assessment, suggesting that districts value the technical support. To support school districts in improving the quality of school wellness policies, we recommend researchers prioritize collaborative dissemination efforts and provide actionable policy data when conducting school wellness policy evaluations.

Background: The Final Rule of the Healthy Hunger Free Kids Act, published in 2016, required school districts participating in the federal Child Nutrition Programs to update their local wellness policies to reflect the more stringent requirements effective June 30, 2017., Objective: Our aim was to investigate whether Wisconsin school wellness policies (SWPs) were updated after the Final Rule, measure policy quality change, and describe mechanisms of successful policy change., Design: From 2016 through 2018, an explanatory sequential mixed-methods study examined change in SWP quality before and after the Final Rule was published. SWPs were collected in 2 waves reflecting policies written before and updated after the July 21, 2016 publication of the Final Rule. Semi-structured key-informant interviews were conducted with districts that demonstrated significant policy improvement., Participants/setting: Quantitative analysis examined 442 Wisconsin school districts' SWPs. Semi-structured interviews were conducted with 14 school districts that demonstrated significant change between waves., Main Outcome Measures: WellSAT 2.0 strength and comprehensiveness scores measured SWP quality among districts that updated their policies. Themes from interviews were identified using framework analysis., Statistical Analysis Performed: First, we calculated the proportion of Wisconsin school districts participating in federal Child Nutrition Programs for which SWPs were obtained at both waves of policy collection (n = 192 districts, 43.4%). Among districts that updated SWPs in wave II, repeated-measure analysis of variance tests described policy quality and policy quality change, respectively., Results: Among the 192 districts that updated their SWPs, policy quality increased overall and for 5 of 6 domains. Nutrition education scores did not show significant change. Interviewees commonly cited wellness leadership, support and resources, and buy-in and culture change as key components of policy improvement., Conclusions: Fewer than half of Wisconsin school districts updated their policies in the 10 months after the Final Rule was published. SWP from these districts showed policy quality improvement in most areas. Interviews with successful districts indicate the common need for empowered leaders and supportive environments to facilitate culture change around student wellness., (Copyright © 2021 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Studying rheological and sensory behaviors of cheese provides structural and texture-related information that could be useful for a better understanding of the complex wear behaviors of cheese and their relationships with cheese industrial and oral processing behaviors. Thus, the objective of this study was to determine the relationships of rheological and sensory properties with cheese wear. Rheological tests including large amplitude oscillatory shear, strain sweeps at different temperatures (5, 15, and 25°C), and large-strain compression at room temperature (22 ± 2°C) were conducted for cheeses with varying fat contents (40, 50, 52, and 54% fat-in-dry-matter aged for different periods (15, 30, 45, and 60 d). Descriptive sensory analysis was used to evaluate cheese sensory texture attributes. Overall, fat content, testing temperature, and aging time had significant impact on cheese viscoelastic parameters. Higher temperature, aging time, and fat content led to lower rigidity and greater extent of nonlinear viscoelastic behaviors in the cheeses. Mass loss showed negative correlations with critical strain (γ c ), critical stress (σ c ), complex modulus (G * ), and fracture stress, but had positive correlations with phase angle (δ) and fracture strain. Sensory data showed that texture attributes were affected by cheese fat content and aging time and had significant correlations with mass loss at high normal force and sliding speed. This study showed that rheology and sensory data can be used to provide fundamental information on the wear behaviors of cheese and other soft materials., (© 2020 Wiley Periodicals LLC.)

In the present work, we determined the structure-function relationships of basil seed gum (BSG) and whey protein isolate (WPI) mixtures at the start of soluble complex formation, maximum soluble complex formation and predominant thermodynamic incompatibility to understand BSG:WPI blends interaction behavior. Accordingly, turbidity and zeta potential were analyzed in the pH range of 2.0-7.0 and BSG:WPI ratios of 1:4, 1:6.6 and 1:9. Dynamic rheometry was used to evaluate samples at three different pHs. Additionally, dilute solution properties of BSG, WPI and their blends were studied at pH = 7.0. Independent of mixture ratio, all dispersions showed maximum interaction at pH = 5.0, the start of soluble complex formation around pH = 6.0 and thermodynamic incompatibility interaction behavior at pH = 7.0. Cole-Cole plots based on dynamic rheometry supported the Gibbs free energy change of mixtures based on intrinsic viscosity data. These results are important to create new structures from mixtures of proteins and polysaccharides., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Rheological properties of food materials are important as they influence food texture, processing properties, and stability. Rotational rheometry has been widely used for measuring rheological properties. However, the measurements obtained using different geometries and rheometers are generally not compared for precision and accuracy, so it is difficult to compare data across different studies. In this study, nine rheometers from seven laboratories were used to measure the viscosity and viscoelastic properties of a commercial salad dressing. The measurements were obtained at three temperatures (8, 25, and 60 °C) using different diameter parallel plates (20, 40, 50, and 60 mm). Generally, the viscosity measurements among rheometers differed significantly ( P < 0.05 ). For larger geometry diameter (40, 50, and 60 mm) and at lower temperatures (8 °C), viscosity measurements at lower shear rate (0.01, 0.1, and 1.0 s -1 ) were significantly different. Rheometer brand significantly affected storage modulus only at low (0.01%) and high levels (10% and 100%) of strain. Temperature was an influencing factor on viscoelastic behaviors only at high strain (>10%). Storage moduli values obtained by frequency sweeps were not affected by rheometer or plate diameter. Overall, rheometer, geometry, and temperature can influence rheological measurements and care should be taken when comparing data across laboratories or published works. Higher shear rates (≥10 s -1 ) and moderate strains (0.1% to 10%) generally provide more repeatable data among different laboratories. PRACTICAL APPLICATION: This study provides information on what factors may potentially influence rheological measurements conducted across different laboratories. It is useful for rheometer users who want to compare their experimental data to published data or compare two sets of published data. It is better to compare data collected at shear rates 10 s -1 and strains between 0.1% and 1.0%., (© 2019 Institute of Food Technologists®.)

Background: We examined written language in Wisconsin school wellness policies (SWPs) for federal mandate compliance, quality related to obesity prevention, and school characteristics associated with variations in quality. This is the first near census of Wisconsin SWPs and examines whether adhering to federal mandates results in strong policies aimed at preventing pediatric obesity., Methods: Policies were coded using the WellSAT 2.0. Policy quality was computed as comprehensiveness and strength based on 6 subscales and 2 overall scores. Variations in policy quality were examined by district size, free/reduced lunch percentage, and year of last revision., Results: We received SWPs from 91% of districts. Six of the 8 federal mandates were addressed by the majority of districts, although less than one fourth addressed all. Most comprehensiveness scores were weak to moderate, and strength scores were weak. All school characteristics were significantly related to overall policy quality; effect sizes were small., Conclusions: Our results confirm the necessity of statewide focus on SWP improvement and suggest that while districts may be meeting federal mandates related to pediatric obesity, few policies include health promotion practices beyond those required. Policies remain fragmented and lack focus on obesity prevention practices; we identify modifiable areas for improvement., (© 2019, American School Health Association.)

Fluid milk may be pasteurized by high-temperature short-time pasteurization (HTST) or ultrapasteurization (UP). Literature suggests that UP increases milk astringency, but definitive studies have not demonstrated this effect. Thus, the objective of this study was to determine the effects of pasteurization method, fat content, homogenization pressure, and storage time on milk sensory and mechanical behaviors. Raw skim (<0.2% fat), 2%, and 5% fat milk was pasteurized in duplicate by indirect UP (140°C, 2.3 s) or by HTST pasteurization (78°C, 15 s), homogenized at 20.7 MPa, and stored at 4°C for 8 wk. Additionally, 2% fat milk was processed by indirect UP and homogenized at 13.8, 20.7, and 27.6 MPa and stored at 4°C for 8 wk. Sensory profiling, instrumental viscosity, and friction profiles of all milk were evaluated at 25°C after storage times of 1, 4, and 8 wk. Sodium dodecyl sulfate PAGE and confocal laser scanning microscopy were used to determine protein structural changes in milk at these time points. Fresh HTST milk was processed at wk 7 for wk 8 evaluations. Ultrapasteurization increased milk sensory and instrumental viscosity compared with HTST pasteurization. Increased fat content increased sensory and instrumental viscosity, and decreased astringency and friction profiles. Astringency, mixed regimen friction profiles, and sensory viscosity also increased for UP versus HTST. Increased storage time showed no effect on sensory viscosity or mechanical viscosity. However, increased storage time generally resulted in increased friction profiles and astringency. Sodium dodecyl sulfate PAGE and confocal laser scanning microscopy showed increased denatured whey protein in UP milk compared with HTST milk. The aggregates or network formed by these proteins and casein micelles likely caused the increase in viscosity and friction profiles during storage. Homogenization pressure did not significantly affect friction behaviors, mechanical viscosity, or astringency; however, samples homogenized at 13.8 MPa versus 20.7 and 27.6 MPa showed higher sensory viscosity. Astringency was positively correlated with the friction coefficient at 100 m/s sliding speed (R 2 = 0.71 for HTST milk and R 2 = 0.74 for UP milk), and sensory viscosity was positively correlated with the mechanical viscosity at a shear rate of 50 s -1 (R 2 = 0.90). Thus, instrumental testing can be used to indicate certain sensory behaviors of milk., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Introduction: The Wisconsin Early Childhood Obesity Prevention Initiative (Initiative), established in 2007, seeks to address and prevent obesity in the early care and education system through nutrition and physical activity environmental and policy changes. The collaborative includes professionals from 3 state of Wisconsin Departments, the University of Wisconsin-Extension, the University of Wisconsin-Madison, and public health and early care and education organizations. This paper explores the efforts of the Initiative to advance our understanding of collective impact in practice and its value to health promotion efforts., Methods: Evaluators conducted a mixed methods case study to evaluate the application of collective impact principles by the Initiative. This included a survey of Initiative partners, review of archival documents, and qualitative interviews with Initiative leaders., Results: Initiative partners noted progress in establishing the conditions for collective impact. Archival documents and interviews describe both formal and informal practices that helped set a common agenda, align and coordinate partner activities, and promote communication among Initiative leaders. Results also detail the important current and potential roles of “backbone” staff from healthTIDE to support the Initiative. Additionally, results suggest particularly challenging aspects of the Initiative’s impact model related to shared measurement and broader stakeholder communication. While the Initiative is still setting in place the conditions for collective impact, it has achieved significant policy, systems, and environment changes since its formation. Inclusion of nutrition and physical activity criteria in the state’s quality rating improvement system for child care centers is one of its outcomes., Conclusions: This case study offers several important insights about the application of collective impact in health promotion efforts, particularly in relation to the transition from previous collaborative activities, the value of establishing a clear common agenda among partners, the roles of backbone staff, and time and partner relationships in collective impact.