Antioxidant rich grape pomace extract suppresses postprandial hyperglycemia in diabetic mice by specifically inhibiting alpha-glucosidase

Abstract Background Postprandial hyperglycemia is an early defect of type 2 diabetes and one of primary anti-diabetic targets. Treatment of postprandial hyperglycemia can be achieved by inhibiting intestinal α-glucosidase, the key enzyme for oligosaccharide digestion and further glucose absorption. Grape pomace is winemaking byproduct rich in bioactive food compounds such as phenolic antioxidants. This study evaluated the anti-diabetic potential of two specific grape pomace extracts by determining their antioxidant and anti-postprandial hyperglycemic activities in vitro and in vivo. Methods The extracts of red wine grape pomace (Cabernet Franc) and white wine grape pomace (Chardonnay) were prepared in 80% ethanol. An extract of red apple pomace was included as a comparison. The radical scavenging activities and phenolic profiles of the pomace extracts were determined through the measurement of oxygen radical absorbance capacity, DPPH radical scavenging activity, total phenolic content and flavonoids. The inhibitory effects of the pomace extracts on yeast and rat intestinal α-glucosidases were determined. Male 6-week old C57BLKS/6NCr mice were treated with streptozocin to induce diabetes. The diabetic mice were then treated with vehicle or the grape pomace extract to determine whether the oral intake of the extract can suppress postprandial hyperglycemia through the inhibition of intestinal α-glucosidases. Results The red grape pomace extract contained significantly higher amounts of flavonoids and phenolic compounds and exerted stronger oxygen radical absorbance capacity than the red apple pomace extract. Both the grape pomace extracts but not the apple pomace extract exerted significant inhibition on intestinal α-glucosidases and the inhibition appears to be specific. In the animal study, the oral intake of the grape pomace extract (400 mg/kg body weight) significantly suppressed the postprandial hyperglycemia by 35% in streptozocin-induced diabetic mice following starch challenge. Conclusion This is the first report that the grape pomace extracts selectively and significantly inhibits intestinal α-glucosidase and suppresses postprandial hyperglycemia in diabetic mice. The antioxidant and anti-postprandial hyperglycemic activities demonstrated on the tested grape pomace extract therefore suggest a potential for utilizing grape pomace-derived bioactive compounds in management of diabetes

Microtearding mode study in NSTX using machine learning enhanced reduced model

This article presents a survey of NSTX cases to study the microtearing mode (MTM) stabilities using the newly developed global reduced model for Slab-Like Microtearing modes (SLiM). A trained neutral network version of SLiM enables rapid assessment (0.05s/mode) of MTM with $98\%$ accuracy providing an opportunity for systemic equilibrium reconstructions based on the matching of experimentally observed frequency bands and SLiM prediction across a wide range of parameters. Such a method finds some success in the NSTX discharges, the frequency observed in the experiment matches with what SLiM predicted. Based on the experience with SLiM analysis, a workflow to estimate the potential MTM frequency for a quick assessment based on experimental observation has been established

Vulnerable Boys: Short-term and Long-term Gender Differences in the Impacts of Adolescent Disadvantage.

The growing gender gap in educational attainment between men and women has raised concerns that the skill development of boys may be more sensitive to family disadvantage than that of girls. Using the National Longitudinal Study of Adolescent to Adult Health (Add Health) data we find, as do previous studies, that boys are more likely to experience increased problems in school relative to girls, including suspensions and reduced educational aspirations, when they are in poor quality schools, less-educated neighborhoods, and father-absent households. Following these cohorts into young adulthood, however, we find no evidence that adolescent disadvantage has stronger negative impacts on long-run economic outcomes such as college graduation, employment, or income for men, relative to women. We do find that father absence is more strongly associated with men's marriage and childbearing and weak support for greater male vulnerability to disadvantage in rates of high school graduation. An investigation of adult outcomes for another recent cohort from the National Longitudinal Survey of Youth, 1997 produces a similar pattern of results. We conclude that focusing on gender differences in behavior in school may not lead to valid inferences about the effects of disadvantage on adult skills

Vulnerable Boys: Short-Term and Long-Term Gender Differences in the Impacts of Adolescent Disadvantage

The growing gender gap in educational attainment between men and women has raised concerns that the skill development of boys may be more sensitive to family disadvantage than that of girls. Using the National Longitudinal Study of Adolescent to Adult Health (Add Health) data we find, as do previous studies, that boys are more likely to experience increased problems in school relative to girls, including suspensions and reduced educational aspirations, when they are in poor quality schools, less-educated neighborhoods, and father-absent households. Following these cohorts into young adulthood, however, we find no evidence that adolescent disadvantage has stronger negative impacts on long-run economic outcomes such as college graduation, employment, or income for men, relative to women. We do find that father absence is more strongly associated with men's marriage and childbearing and weak support for greater male vulnerability to disadvantage in rates of high school graduation. An investigation of adult outcomes for another recent cohort from the National Longitudinal Survey of Youth, 1997 produces a similar pattern of results. We conclude that focusing on gender differences in behavior in school may not lead to valid inferences about the effects of disadvantage on adult skills

Caspase-1 activation and mature interleukin-1β release are uncoupled events in monocytes

AIM: To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β (pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events. METHODS: All experiments were performed on fresh or overnight cultured human peripheral blood monocytes (PBMCs) that were isolated from healthy donors. PBMCs were activated by lipopolysaccharide (LPS) stimulation before being treated with Adenosine triphosphate (ATP, 1 mmol/L), human α-defensin-5 (HD-5, 50 μg/mL), and/or nigericin (Nig, 30 μmol/L). For each experiment, the culture supernatants were collected separately from the cells. Cell lysates and supernatants were both subject to immunoprecipitation with anti-IL-1β antibodies followed by western blot analysis with anti-caspase-1 and anti-IL-1β antibodies. RESULTS: We found that pro-IL-1β was processed to mature IL-1β in LPS-activated fresh and overnight cultured human monocytes in response to ATP stimulation. In the presence of HD-5, this release of IL-1β, but not the processing of pro-IL-1β to IL-1β, was completely inhibited. Similarly, in the presence of HD-5, the release of IL-1β, but not the processing of IL-1β, was significantly inhibited from LPS-activated monocytes stimulated with Nig. Finally, we treated LPS-activated monocytes with ATP and Nig and collected the supernatants. We found that both ATP and Nig stimulation could activate and release cleaved caspase-1 from the monocytes. Interestingly, and contrary to IL-1β processing and release, caspase-1 cleavage and release was not blocked by HD-5. All images are representative of three independent experiments. CONCLUSION: These data suggest that caspase-1 activation/processing of pro-IL-1β by caspase-1 and the release of mature IL-1β from human monocytes are distinct and separable events

Testing the illustrative method: How to reveal hidden knowledge stored in traditional water systems

The polder-boezem system, a traditional water system, is a stepping-up discharge system that drains water from the lowlands into the outer water of rivers and sea. In order to reveal the landscape architectonic structure and form of the Dutch polder-boezem system the form-layer method (Steenbergen et al. 2005) was applied and extended in the dissertation: The Landscape Architecture of the Polder-boezem system, structure and form of water network, water pattern and water work in the Dutch lowlands (Bobbink 2016). Originally the form-layer method is an analytic tool to understand the structure and form relation between a landscape architectonic composition (a project) and it’s site. Four layers are distinguished: the basic form, in which the relation between the intervention and the topography is unfolded; the program form, in which the structure and form of the intervention in relation to its program is clarified; the image form, in which the cultural and metaphorical expression is linked to the structure and form of the landscape and the layer of the spatial form, in which the structure and form of landscape and intervention is defined from the experience on eyelevel perspective. In the dissertation the method was used and adapted to analyse a cultural landscape (the polder landscape) instead of a landscape architectonic design. After identifying the landscape architecture form and structure of the lowland water system we felt the need to extend the method further to reveal the use, maintenance and the circularity of humanmade traditional water systems in general.Humans transformed and manage natural water flow in an particular area during decades for different kinds of reasons. Depending on its scale these water management measures shaped the landscape. Indigenous water systems are interesting study objects because they develop over a long period of time by trial and error, cut and fill and therefore store a lot of knowledge related to use, adaptation and climate variation. Many different water elements and works are developed to direct, drain, irrigate, retain, infiltrate and reuse water. Commonly different water elements and works are combined in one system, in which they most of the time try to keep the water in place as long as possible. Next to the benefit for humans, traditional water systems are relevant and valuable for ecosystem services due to their size and connecting capacity as part of blue-green networks.The extended method, called ‘the illustrative method’ (Bobbink and Ruy, 2017) is tested by international graduate students and researchers of the TU Delft, section of Landscape Architecture in the Circular Water Stories LAB. All students within the LAB are interested in water topics and want to learn from existing systems. Nine traditional water systems are mapped according to the method. By evolving the drawings simultaneous a set of theme-drawings and diagrams, flanked by one legend for all cases is developed. Every drawing is drawn again and again until the best result, a meaningful drawing is achieved. Students and researchers learn from each other. During the process the understanding of which layers (soil map, height maps, relief etc.) need to be combined to express the essence of the waterscape have become clearer. From here the description of the method is explicated. Each set of drawings include: a short introduction, a description of the project, photos of the past and today; diagrams of the climate zone including the rain fall curve over the year and a diagram presenting the flow directions of the system; the water system drawn on the regional scale in relation to the topographical and soil map; the development of the water system over a longer time period, a more technical drawing of the catchment area and the different water compartments; sections and/or diagrams in which the interaction between the water elements, water works, its ecology and the use is explained; a crucial detail which is representative for the system and a conclusion. In the conclusion students summarized their findings of the analyses by transforming general values into specific values. So far we came up with six values.Landscape values: natural landscapes are transformed to cultural landscapes, through transformation the natural landscape is architectonically pronounced and is part of the cultural expression; Strategic values: smart use of the site to achieve maximum profitability with the minimum resources and infrastructures, by taking advantage of natural elements, topographic changes, slopes, river bends...; Functional values: water systems are constructions with simple formal and practical solutions; Material and tangible values: water elements and water works are a source of knowledge of traditional construction techniques, local materials from the surrounding area are used that adapt to climate and lithology, expression of rituals; Values of sustainability and circularity: by using materials of the surroundings and non-polluting materials by using natural local materials. The water is used in the system for different purposes and brought back into the natural circuit;Ethnographic and identity values: to encompass the knowledge of what was the main activities of the region. The process of testing the method made clear that a lot of work is involved, especially for those cases which are situated in countries that do not have open access to data. Sites need to be reconstructed with the help of google earth maps. Computer and analytical skills are needed to process the amount of data. Examples help to figure out the path of the analyses. A description of the method is not enough to get a good result, intensive discussions are needed to improve the drawings. Comparison of cases and ongoing reflection is essential for a valuable outcome of the research, this still needs to be done. For now (march 2019) the material is on display in an exhibition at TU Delft and waits for comments of peers. The new input can help to develop the method further and to come up with more circular traditional water systems that in the end can be published in a book. The graduation LAB is called ‘Circular Water Stories’ but so far we did not manage to work on the story part, since this involves more research, research in which we involve the makers and users of the system and dive into achieves to learn more about its history. Knowledge stored in traditional water systems can inspire spatial, smart and sustainable approaches on water management (Ryu 2012). To design with water, one has to understand the geomorphology of the landscape, the operation of the natural water system and its transformation in order to relate to it. The work of the students proves that the illustrative method can be used regardless of scale, complexity and cultural background of the water system to reveal knowledge on the relation between landscape, water management and people. In general the research on traditional water systems delivers first of all knowledge from the past for sustainable, adaptive water design. For the students the analytical work at this stage delivers tools for their final design-thesis.<br/

A new model for the membrane topology of glucose-6-phosphatase: the enzyme involved in Von Gierke disease

AbstractVery recently we have proposed [Hemrika et al. (1997) Proc. Natl. Acad. Sci. USA 94, 2145–2149] that the active site of the vanadate-containing chloroperoxidase from the fungus Curvularia inaequalis, of which the tertiary structure is known, is structurally very similar to that of the membrane-bound mammalian glucose-6-phosphatases for which no structural data are available. The proposed active site of glucose-6-phosphatase, however, is incompatible with the six transmembrane–helix topology model that is currently used. Here we present a new topology model for glucose-6-phosphatase which is in agreement with all available data