Betydning av kostholdsfaktorer og reaktive oksygenforbindelser (ROS) for tarmen og dens mikrobiota i en musemodell med lavgrads inflammasjon

Background: Various factors, including dietary components, the gut microbiota and host responses, are imperative for gut health. Optimal interactions between diet, gut microbiota and host are suggested to be important to avoid imbalanced gut microbial ecosystems and low-grade inflammation. Dietary fiber components, in particular, have been highlighted for their positive effects on the microbiota and gut inflammation status. Furthermore, although high-fat diets, mainly based on animal fat, have been associated with gut inflammation it is not clear to what extend different fat sources (i.e., animal type), and modes of fat intake affect the gut inflammatory process. Objectives: The overall aim of the current thesis was to investigate the differential impact of fiber and protein fractions from faba beans and different fat types on the microbiota composition and gut health in mice with and without low-grade inflammation in the gut. Another aim was to assess the role of reactive oxygen species (ROS) induced by NADPH oxidase 1 (NOX1) for low-grade gut inflammation and microbial community in the colon. Methods: After the establishment of a low-grade inflammation model with the chemical dextran sodium sulfate (DSS) feeding trials with C57BL/6J mice were performed. Besides the wild type (WT), C57BL/6J, mice deficient in the NOX1 gene were used (NOX1-KO mice). The diets offered during the mouse experiments varied in macronutrient composition and energy intake. Briefly these diets were: a standard mouse diet (chow diet), a synthetic low-fat diet (LFD), a purified western diet (WD) and modified western diets (WDs), in which defined fractions from faba beans were incorporated. These fractions were protein fraction (PF) and fiber fraction (FF) that replaced partially casein and cellulose substances in WDs, respectively. Body weight, colon length, gene expression of inflammatory and reactive oxygen species related genes, biomarkers of inflammation in blood and fecal sample were parameters to be examined. Shifts of the colonic microbiota populations in phylum and genus level upon the termination of experiments were additionally evaluated using LEfSe (Linear discriminant analysis Effect Size). Results: In Paper I, we established the low-grade inflammation mouse model and showed that NOX1 plays a significant role in ROS formation in the colon during pathogenesis towards the status of low-grade inflammation. We demonstrated that NOX1 modulates the colonic microbiota both in a steady-state (healthy) and during low grade inflammation. Also, while absence of NOX-1 did not influence the pathology scores, the inflammation-related genes and lipocalin 2 (LCN-2) expression tended to be higher in NOX1 deficient mice than in WT mice. From these results we conclude that NOX1-dependent ROS production is important for shaping microbiota composition and for protecting against insults to the colon. In Paper II, we compared the impact of a low-fat diet (LFD) and different western diets (WD) with fat from various sources on colon health in low-grade inflammation. We falsified the hypothesis that WD fed mice would manifest more severe symptoms compared to LFD fed mice as we observed that LFD mice were more susceptible to DSS-induced inflammation and revealed a less diverse microbiota with increased relative abundance of the Proteobacteria phylum compared to WD fed mice. Both fat sources (milk and lard) tested as part of the WD induced similar immediate ‘protective’ effect as compared to the LFD. Because these results contradict many other studies, we suspect that the higher fat content protects against the establishment of the DSS-induced low-grade inflammation. Therefore, we raise the concern that the DSS model of mouse inflammation might be unfit for the purpose of studying the differential impact of dietary fats. In Paper III, we investigated possible metabolic and colonic beneficial effects of faba bean protein and fiber fractions when ingested as part of a WD. Although the diets were isocaloric the mice that ingested diets with added faba bean protein content (WD+PF and WD+BF) had a higher increase in body weight compared to the pure WD or the WD+FF. However, no differences were revealed in glucose and insulin tolerance test between dietary groups. Also, neither the protein nor the fiber fraction protected against DSS induced low-grade gut inflammation as compared with mice fed a pure WD. Furthermore, marginal changes were found in the microbiota at the genus level. Conclusions: Collectively, our results demonstrate a role for ROS in the healthy gut and in response to DSS induced inflammation which may be related to controlling and shaping the microbiota. Furthermore, unexpectedly, we found that a high fat content in the diet protected against DSS induced inflammation as compared with the LFD group and speculate that the high fat content confounds the establishment of the DSS induced low-grade inflammation model. Also, a WD with a higher protein fraction from faba bean resulted in even higher gain of weight compared to standard WD. Only marginal changes were found for the microbiota composition when increasing the fiber fraction of the WD and it did not protect against weight gain.Bakgrunn: Ulike faktorer, slik som næringsstoffer, tarmmikrobiota og biologiske vertsresponser, er avgjørende for tarmhelsen. Optimal interaksjon mellom disse er viktig for å unngå ubalanserte mikrobielle tarmøkosystemer og lavgradig betennelse. Særlig har kostfiber blitt fremhevet som viktig og positiv for både mikrobiota og tarmbetennelsesstatus. I tillegg, selv om kosthold med høyt fettinnhold fra animalske kilder har vært assosiert med tarmbetennelse, er det ikke entydig klart i hvilken grad ulike fettkilder (dvs. dyretype), og inntak av fett som sådan påvirker betennelse i tarm. Mål: Det overordnede målet med denne oppgaven var å undersøke i hvilken grad fiber- og proteinfraksjoner fra fababønner og ulike fetttyper påvirket mikrobiotasammensetningen og tarmhelsen hos mus med og uten lavgradig betennelse i tarmen. Et annet mål var å evaluere rollen til reaktive oksygenforbindelser (ROS) indusert av NADPH-oksidase 1 (NOX1) for lavgradig tarmbetennelse og mikrobielle samfunn i tykktarm. Metoder: Etter etablering av en lavgradig inflammasjonsmodell med det kjemiske stoffet dekstran-natriumsulfat/dextran sodium sulfate (DSS) ble det utført fôringsforsøk med C57BL/6J-mus. I tillegg til å bruke villtypemus (WT), ble C57BL/6J-mus uten uttrykk av NOX1-genet benyttet (NOX1-KO-mus). De ulike fôrtypene som ble brukt under museforsøkene varierte i sammensetning av makronæringsstoffer og energiinnhold. Fôrtypene bestod (i korthet) av: standard musefôr også kalt chow, lav-fettdiett (LFD), en vestlig høy-fettdiett (WD) og modifiserte vestlige dietter, der fraksjoner fra faba bønner ble inkorporert. Disse fraksjonene var proteinfraksjon (PF) og fiberfraksjon (FF) som delvis erstattet henholdsvis kasein- og cellulose i WD-fôrtypene. Alle fôrtypene med unntak av chow var kontrollerte (kjent innhold av alle næringsstoffene og ingrediensene). Chow-fôret er mer udefinert fordi det er satt sammen av hele råvarer. Kroppsvekt, tykktarmslengde, genuttrykk av inflammatoriske og ROS-relaterte gener, biomarkører for betennelse i blod og avføringsprøver var parametere som skulle undersøkes. Endringer av tykktarmens mikroflora ved avslutning av eksperimenter ble i tillegg evaluert ved bruk av såkalt LefSe (Linear discriminant analysis Effect size). Resultater: I Artikkel I (Paper I) etablerte vi musemodell for lavgradig inflammasjon og viste at NOX1 spiller en betydelig rolle i ROS-produksjon i tykktarmen under lavgradig betennelse indusert med DSS. Vi viste også at NOX1 modulerer tykktarmsmikrobiotaen både i en ‘steady-state’ (sunn) og under lavgradig betennelse. Videre så vi at, mens fravær av NOX-1 ikke påvirket patologi, hadde de betennelsesrelaterte genene og uttrykk av lipocalin 2 (LCN-2) en tendens til å være høyere i NOX1-knockout mus enn i WT-mus. Fra disse resultatene konkluderer vi med at NOX1-avhengig ROS-produksjon er viktig for å forme mikrobiotasammensetning og for å beskytte mot skader i tykktarmen. I Artikkel II (Paper II) sammenlignet vi effekten av en lav-fettdiett (LFD) og ulike vestlige dietter (WD) med fett fra ulike kilder på tykktarmshelsen ved lavgradig betennelse. Vi forkastet derfor hypotesen om at WD-fôrede mus ville manifestere mer alvorlige symptomer sammenlignet med LFD-fôrede mus da vi observerte at LFD-mus var mer mottakelige for DSS-indusert betennelse og avslørte en mindre mangfoldig mikrobiota med økt relativ tilstedeværelse av Proteobakterier (fylum) sammenlignet med WD-fôrede mus. Begge fettkilder (melk og svinefett) testet som en del av WD førte i begge tilfeller til umiddelbar "beskyttende" effekt sammenlignet med LFD. Fordi disse resultatene motsier mange andre studier, mistenker vi at det høyere fettinnholdet beskytter mot etableringen av DSS-indusert lavgradig betennelse. Derfor reiser vi bekymringen for at DSS-modellen for musebetennelse kan være uegnet for det formål å studere den differensielle påvirkningen av fettrikt fôr med den hensikt å studere fysiologiske effekter av høyfett-dietter. I Artikkel II (Paper III) undersøkte vi potensielt metabolske effekter av proteiner og fiber (begge var fraksjoner) isolert fra fababønner som ble blandet inn WD-fôret. Selv om diettene var isokaloriske, hadde musene som inntok fôret beriket med proteiner fra fababønner (WD+PF og WD+BF) fant vi at disse musene hadde en høyere økning i kroppsvekt sammenlignet med ren WD eller WD+FF (fiberfraksjon). Imidlertid ble det ikke avdekket forskjeller i glukose- og insulinregulering mellom de ulike diettgruppene. Heller ikke protein- eller fiberfraksjonen fra fababønner beskyttet mot DSS induserte lavgradig tarmbetennelse sammenlignet med mus som ble fôret med en ren WD. Videre ble det funnet marginale endringer i mikrobiotaen på slektsnivå. Konklusjoner: Samlet viser resultatene våre en rolle for ROS i den sunne tarmen og som respons på DSS-indusert betennelse som kan være relatert til å kontrollere og forme mikrobiotaen. Videre, og noe uventet, fant vi at et høyt fettinnhold i kostholdet (WD) beskyttet mot DSS-indusert betennelse sammenlignet med LFD-gruppen og spekulerer i at det høye fettinnholdet påvirker etableringen av den DSS-induserte lavgradige betennelsesmodellen, muligens direkte. Dessuten resulterte en WD med en høyere proteinfraksjon fra fababønne i enda høyere vektøkning sammenlignet med standard WD. Bare marginale endringer ble funnet for mikrobiotasammensetningen ved tilsetning av fiberfraksjonen til WD, og den beskyttet ikke mot vektøkning

Election Laws and Voter Turnout in the United States

Over the last decade, electoral reform has become a topic of intense controversy in the United States. While Republicans highlight the need for strict voting laws to prevent voter fraud and maintain election integrity, Democrats argue that these laws create barriers to voting and decrease voter turnout. How have U.S. voting laws evolved over the last decade? How do these changes affect voter turnout? Which voting laws have the greatest impact on voter turnout? Researchers Larocca and Klemanski (2011) provide answers to some of these questions through an empirical analysis on the effects of state-level election laws and reforms on voter turnout in the 2000, 2004, and 2008 presidential elections. Using a cost-benefit model, the authors find evidence to support their hypothesis: reducing both the number of trips and the number of tasks required to vote has the most positive impact on voter turnout. Building on this I hypothesize that states with more restrictive voter laws will have a lower voter turnout than states with less restrictive voter laws. I also hypothesize that voter registration deadlines will have the greatest impact on voter turnout. Compiling state-level data on early in-person voting, absentee voting, voter identification requirements, and voter registration deadlines from 2012, 2016, and 2020, I use linear regression to analyze the effects of the average restrictiveness of voting laws on voter turnout. The results of this model reveal that voting law restrictiveness has a highly suggestive effect on voter turnout. As the average restrictiveness of voting laws increased, voter turnout decreased anywhere from 4.7 to 8.0 percent. In addition, voter registration deadlines had a significant impact on voter turnout in all three election years. These results provide compelling implications for future policy proposals regarding election laws. They also pose interesting questions for future research relating to who is most affected by these voting laws

Sweet cherry:composition, postharvest preservation, processing and trends for its future use

Background Sweet cherries (Prunus avium L.) are a nutritious fruit which are rich in polyphenols and have high antioxidant potential. Most sweet cherries are consumed fresh and a small proportion of the total sweet cherries production is value added to make processed food products. Sweet cherries are highly perishable fruit with a short harvest season, therefore extensive preservation and processing methods have been developed for the extension of their shelf-life and distribution of their products. Scope and Approach In this review, the main physicochemical properties of sweet cherries, as well as bioactive components and their determination methods are described. The study emphasises the recent progress of postharvest technology, such as controlled/modified atmosphere storage, edible coatings, irradiation, and biological control agents, to maintain sweet cherries for the fresh market. Valorisations of second-grade sweet cherries, as well as trends for the diversification of cherry products for future studies are also discussed. Key Findings and Conclusions Sweet cherry fruit have a short harvest period and marketing window. The major loss in quality after harvest include moisture loss, softening, decay and stem browning. Without compromising their eating quality, the extension in fruit quality and shelf-life for sweet cherries is feasible by means of combination of good handling practice and applications of appropriate postharvest technology. With the drive of health-food sector, the potential of using second class cherries including cherry stems as a source of bioactive compound extraction is high, as cherry fruit is well-known for being rich in health-promoting components

Encapsulation of citrus by-product extracts by spray-drying and freeze-drying using combinations of maltodextrin with soybean protein and ι-carrageenan

The effect of different combinations of maltodextrin (MD) coating agents (MD, MD + soybean protein, and MD + ι-carrageenan) on the encapsulation of lemon by-product aqueous extracts using freeze-drying and spray-drying were investigated. The total phenolic content (TPC), total flavonoid content (TFC), and ferric ion reducing antioxidant power (FRAP) of the microparticles were evaluated. Freeze-drying with the mixture of MD + soybean protein resulted in the highest retention of TPC, TFC, and FRAP (1.66 ± 0.02 mg GAE/g d.b., 0.43 ± 0.02 mg CE/g d.b., and 3.70 ± 0.05 mM TE/g, respectively). Freeze-drying resulted in microparticles with lower moisture content (MC) and water activity (aw) than those produced by spray-drying. Specifically, the MC and aw of the microparticles produced by freeze-drying ranged from 1.15 to 2.15% and 0.13 to 0.14, respectively, while the MC and aw of the microparticles produced by spray-drying ranged from 6.06% to 6.60% and 0.33 to 0.40, respectively. Scanning electron microscopy revealed that spray-drying resulted in the formation of spherical particles of different sizes regardless of the type of coating agent. Although freeze-drying resulted in microparticles with amorphous glassy shapes, the mixture of MD + soybean protein resulted in the formation of spherical porous particles. X-ray diffraction revealed a low degree of crystallinity for the samples produced by both techniques.</p

Aerodynamic Shape Optimization using the truncated Newton Method and Continuous Adjoint

This paper presents the development and application of the Truncated Newton (TN) method for shape optimization problems based on continuous adjoint. The method is presented for laminar, incompressible flows. OpenFOAM R is chosen as the CFD toolbox in which the method is developed. The Newton equations are solved using the restarted linear GMRES algorithm which requires only the product of the Hessian matrix of the objective function (with respect to the design variables) with a vector. This overcomes the cost for computing the Hessian matrix itself, which unfortunately scales with the number of design variables. The computation of Hessian-vector products is conducted via the combination of continuous adjoint and direct differentiation that gives the minimum cost. The developed method is used for the shape optimization of two 3D ducts and the speed-up gained compared to rival methods is showcased. This research was funded from the People Programme (ITN Marie Curie Actions) of the European Union’s 7 th Framework Programme (FP7/2007-2013) under REA Grant Agreement 317006 (AboutFLOW). The first author is an AboutFLOW Early Stage Researche

Conjugate heat transfer shape optimization based on the continuous adjoint method

In this paper, the continuous adjoint method for use in gradient-based op- timization methods for coupled problems including heat transfer between bodies (solids) and fluids flowing over or inside them is developed. This kind of problems are usually referred to as Conjugate Heat Transfer (CHT) problems. Emphasis is given to expand- ing the Enhanced-Surface Integral (E-SI) adjoint formulation recently published by the authors’ group for shape optimization problems in fluid mechanics only, to tackle CHT problems. This formulation ensures that the gradient of the objective function is accu- rately computed, while the computational cost is kept as low as possible

Impact of different solvents on the recovery of bioactive compounds and antioxidant properties from lemon (Citrus limon L.) pomace waste

The effects of different solvents on the recovery of (i) extractable solids (ES), (ii) total phenolic compounds (TPC), (iii) total flavonoid content (TFC), (iv) vitamin C, and (v) antioxidant activity from lemon pomace waste were investigated. The results revealed that solvents significantly affected the recovery of ES, TPC, TFC, and antioxidant properties. Absolute methanol and 50% acetone resulted in the highest extraction yields of TPC, whereas absolute methanol resulted in the highest extraction of TFC, and water had the highest recovery of vitamin C. 50% ethanol, and 50% acetone had higher extraction yields for TPC, and TFC, as well as higher antioxidant activity compared with their absolute solvents and water. TPC and TFC were shown to be the major components contributing to the antioxidant activity of lemon pomace

Optimizing a sustainable ultrasound assisted extraction method for the recovery of polyphenols from lemon by-products:comparison with hot water and organic solvent extractions

Response surface methodology (RSM) based on a three-factor and three-level Box–Behnken design was employed for optimizing the aqueous ultrasound-assisted extraction (AUAE) conditions, including extraction time (35–45 min), extraction temperature (45–55 °C) and ultrasonic power (150–250 W), for the recovery of total phenolic content (TPC) and rutin from lemon by-products. The independent variables and their values were selected on the basis of preliminary experiments, where the effects of five extraction parameters (particle size, extraction time and temperature, ultrasonic power and sample-to-solvent ratio) on TPC and rutin extraction yields were investigated. The yields of TPC and rutin were studied using a second-order polynomial equation. The optimum AUAE conditions for TPC were extraction time of 45 min, extraction temperature of 50 °C and ultrasonic power of 250 W with a predicted value of 18.10 ± 0.24 mg GAE/g dw, while the optimum AUAE conditions for rutin were extraction time of 35 min, extraction temperature of 48 °C and ultrasonic power of 150W with a predicted value of 3.20 ± 0.12 mg/g dw. The extracts obtained at the optimum AUAE conditions were compared with those obtained by a hot water and an organic solvent conventional extraction in terms of TPC, total flavonoid content (TF) and antioxidant capacity. The extracts obtained by AUAE had the same TPC, TF and ferric reducing antioxidant power as those achieved by organic solvent conventional extraction. However, hot water extraction led to extracts with the highest flavonoid content and antioxidant capacity. Scanning electron microscopy analysis showed that all the extraction methods led to cell damage to varying extents

Relaxing door-to-door matching reduces passenger waiting times: a workflow for the analysis of driver GPS traces in a stochastic carpooling service

Carpooling has the potential to transform itself into a mass transportation mode by abandoning its adherence to deterministic passenger-driver matching for door-to-door journeys, and by adopting instead stochastic matching on a network of fixed meeting points. Stochastic matching is where a passenger sends out a carpooling request at a meeting point, and then waits for the arrival of a self-selected driver who is already travelling to the requested meeting point. Crucially there is no centrally dispatched driver. Moreover, the carpooling is assured only between the meeting points, so the onus is on the passengers to travel to/from them by their own means. Thus the success of a stochastic carpooling service relies on the convergence, with minimal perturbation to their existing travel patterns, to the meeting points which are highly frequented by both passengers and drivers. Due to the innovative nature of stochastic carpooling, existing off-the-shelf workflows are largely insufficient for this purpose. To fill the gap in the market, we introduce a novel workflow, comprising of a combination of data science and GIS (Geographic Information Systems), to analyse driver GPS traces. We implement it for an operational stochastic carpooling service in south-eastern France, and we demonstrate that relaxing door-to-door matching reduces passenger waiting times. Our workflow provides additional key operational indicators, namely the driver flow maps, the driver flow temporal profiles and the driver participation rates