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Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source

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World Journal of Gastroenterology 2019年第33期25卷 4904-4920页

作者： Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane jens christian nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen Cardiovascular Renal and Metabolic DiseasesMedImmuneGaithersburgMD 20878United States Pharmacology GubraH■rsholm DK-2970Denmark

BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.

关键词： Non-alcoholic steatohepatitis High-fat diet Mouse model Histopathology Fibrosis Liver biopsy Liver transcriptome

Advanced brain organoids for neuroinflammation disease modeling

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Neural Regeneration Research 2024年第1期19卷 154-155页

作者： Sonia Sabate-Soler Henry Kurniawan jens christian Schwamborn Luxembourg Centre for Systems Biomedicine University of LuxembourgEsch-sur-AlzetteLuxembourg

Brain organoids mimic closely the embryonic human brain:Over the last decade,the development of human organoid systems has evolved rapidly.Different tissues have been modeled with organoids,such as the gut,lung,liver,kidney retina and brain.These systems have a high cellular heterogeneity,with many cell types integrated into the same system.Organoids'cellular populations interact between and amongst each other in a cellular and molecular level,which represents an advantage with respects to monolayer 2D cell culture systems.

关键词： inflammation lung kidney

Wear dependent virtual flow rate sensor for progressing cavity pumps with deformable stator

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Petroleum Science 2024年第2期21卷 1346-1353页

作者： jens Müller Sebastian Leonow Johannes Schulz christian Hansen Martin Monnigmann Ruhr-Universitat Bochum Universit atsstraûe 150Bochum44801Germany SEEPEX GmbH Scharnh olzstraûe 344Bottrop46240Germany

This contribution presents a novel wear dependent virtual flow rate sensor for single stage single lobe progressing cavity pumps. We study the wear-induced material loss of the pump components and the impact of this material loss on the volumetric efficiency. The results are combined with an established backflow model to implement a backflow calculation procedure that is adaptive to wear. We use a laboratory test setup with a highly abrasive fluid and operate a pump from new to worn condition to validate our approach. The obtained measurement data show that the presented virtual sensor is capable of calculating the flow rate of a pump being subject to wear during its regular operation.

关键词： Backflow Progressing cavity pump Virtual sensor Wear

Small mammal community composition impacts bank vole (Clethrionomys glareolus) population dynamics and associated seroprevalence of Puumala orthohantavirus

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Integrative Zoology 2024年第1期19卷 52-65页

作者： Felicitas Maria BUJNOCH Daniela REIL Stephan DREWES Ulrike MROSENFELD Rainer G.ULRICH jens JACOB christian IMHOLT Julius Kühn-Institute Federal Research Centre for Cultivated PlantsInstitute for Epidemiology and Pathogen DiagnosticsRodent ResearchMünsterGermany University of Münster Institute for Evolution and BiodiversityMünsterGermany Friedrich-Loeffler-Institut Federal Research Institute for Animal HealthInstitute of Novel and Emerging Infectious DiseasesGreifswald-Insel RiemsGermany

Rodents are important reservoirs for zoonotic pathogens that cause diseases in humans.Biodiversity is hypoth-esized to be closely related to pathogen prevalence through multiple direct and indirect pathways.For example,the presence of non-host species can reduce contact rates of the main reservoir host and thus reduce the risk of transmission(“dilution effect”).In addition,an overlap in ecological niches between two species could lead to increased interspecific competition,potentially limiting host densities and reducing density-dependent pathogen transmission processes.In this study,we investigated the relative impact of population-level regulation of direct and indirect drivers of the prevalence of Puumala orthohantavirus(PUUV)in bank voles(Clethrionomys glareolus)during years with high abundance.We compiled data on small mammal community composition from four regions in Germany between 2010 and 2013.Structural equation modeling revealed a strong seasonality in PUUV control mechanisms in bank voles.The abundance of shrews tended to have a negative relationship with host abundance,and host abundance positively influenced PUUV seroprevalence,while at the same time increasing the abundance of competing non-hosts like the wood mouse(Apodemus sylvaticus)and the yellow-neckedfield mouse(Apodemusflavicollis)were associated with reduced PUUV seroprevalence in the host.These results indicate that for PUUV in bank voles,dilution is associated with increased interspecific competition.Anthropogenic pressures leading to the decline of Apodemus spp.in a specific habitat could lead to the amplification of mechanisms promoting PUUV transmission within the host populations.

关键词： bank vole biodiversity Puumala orthohantavirus small mammals

Influence of railway wheel tread damage on wheel-rail impact loads and the durability of wheelsets

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Railway Engineering Science 2024年第1期32卷 20-35页

作者： Michele Maglio Tore Vernersson jens C.O.nielsen Anders Ekberg Elena Kabo CHARMEC Department of Mechanical and Maritime SciencesChalmers University of TechnologySE‑41296 GothenburgSweden

Dynamic wheel-rail contact forces induced by a severe form of wheel tread damage have been measured by a wheel impact load detector during full-scale field tests at different vehicle speeds.Based on laser scanning,the measured three-dimensional damage geometry is employed in simulations of dynamic vehicle-track interaction to calibrate and verify a simulation model.The relation between the magnitude of the impact load and various operational parameters,such as vehicle speed,lateral position of wheel-rail contact,track stiffness and position of impact within a sleeper bay,is investigated.The calibrated model is later employed in simulations featuring other forms of tread damage;their effects on impact load and subsequent fatigue impact on bearings,wheel webs and subsurface initiated rolling contact fatigue of the wheel tread are assessed.The results quantify the effects of wheel tread defects and are valuable in a shift towards condition-based maintenance of running gear,and for general assessment of the severity of different types of railway wheel tread damage.

关键词： Wheel tread damage Rolling contact fatigue cluster Field measurements Dynamic vehicle-track interaction Wheel-rail impact load Wheelset durability

Metabolic collaboration between cells in the tumor microenvironment has a negligible effect on tumor growth

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The Innovation 2024年第2期5卷 107-114页

作者： Johan Gustafsson Fariba Roshanzamir Anders Hagnestål Sagar M.Patel Oseeyi I.Daudu Donald F.Becker Jonathan L.Robinson jens nielsen Department of Life Sciences Chalmers University of TechnologySE-41296 GothenburgSweden Hagnesia AB SE-43854 HindåsSweden Department of Biochemistry and Redox Biology Center University of Nebraska-LincolnLincolnNE 68588USA BioInnovation Institute DK2200 CopenhagenDenmark

The tumor microenvironment is composed of a complex mixture of different cell types interacting under conditions of nutrient deprivation,but the metabolism therein is not fully understood due to difficulties in measuring metabolic fluxes and exchange of metabolites between different cell types in vivo.Genome-scale metabolic modeling enables estimation of such exchange fluxes as well as an opportunity to gain insight into the metabolic behavior of individual cell types.Here,we estimated the availability of nutrients and oxygen within the tumor microenvironment using concentration measurements from blood together with a metabolite diffusion model.In addition,we developed an approach to efficiently apply enzyme usage constraints in a comprehensive metabolic model of human cells.The combined modeling reproduced severe hypoxic conditions and the Warburg effect,and we found that limitations in enzymatic capacity contribute to cancer cells’preferential use of glutamine as a substrate to the citric acid cycle.Furthermore,we investigated the common hypothesis that some stromal cells are exploited by cancer cells to produce metabolites useful for the cancer cells.We identified over 200 potential metabolites that could support collaboration between cancer cells and cancer-associated fibroblasts,but when limiting to metabolites previously identified to participate in such collaboration,no growth advantage was observed.Our work highlights the importance of enzymatic capacity limitations for cell behaviors and exemplifies the utility of enzyme-constrained models for accurate prediction of metabolism in cells and tumor microenvironments.

关键词： metabolism effect limitations

Editorial for “Biointelligent manufacturing in Memorium of Arnold (Arny) L. Demain”

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Synthetic and Systems Biotechnology 2022年第4期7卷 1185-1186页

作者： Qiang Gao jens nielsen Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education College of BiotechnologyTianjin University of Science and TechnologyTianjin300457China BioInnovation Institute Ole Maaloes Vej 3Copenhagen NDK2200Denmark

Biointelligent manufacturing is currently at the center of industrial biotechnology.Industrial biotechnology has historic roots dating thousand years back where microbial fermentation was used to preserve foods,make bread and fermented drinks,but has risen to a modern industry.Much of the development into a modern industry was driven initially by production of antibiotics and later by production of food and feed ingredients.In this development,the late MIT emeritus Professor Arnold(Arny)Lester Demain was one of the drivers and is considered one of the founders of industrial biotechnology.His research founds wide applications and he stands as one of the giants in the field of industrial microbiology and biotechnology[1-7].

关键词： Arnold biotechnology initially

Ethyl-iophenoxic acid as a quantitative bait marker for small mammals

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Integrative Zoology 2022年第6期17卷 981-990页

作者： Kyra JACOBLINNERT christian IMHOLT Detlef SCHENKE jens JACOB Julius Kühn Institute(JKI) Federal Research Centre for Cultivated PlantsInstitute for Plant Protection in Horticulture and ForestsVertebrate ResearchMünsterGermany Department of Behavioral Biology University of OsnabrückOsnabrückGermany Julius Kühn Institute(JKI) Federal Research Centre for Cultivated PlantsInstitute for Ecological ChemistryPlant Analysis and Stored Product ProtectionBerlinGermany

Bait markers are indispensable for ecological research but in small mammals,most markers are invasive,expensive and do not enable quantitative analyses of consumption.Ethyl-iophenoxic acid(Et-IPA)is a non-toxic,quantitative bait marker,which has been used for studying bait uptake in several carnivores and ungulates.We developed a bait with Et-IPA,assessed its palatability to common voles(Microtus arvalis),and determined the dose-residue-relation for this important agricultural pest rodent species.Et-IPA concentrations of 40 to 1280μg Et-IPA per g bait were applied to wheat using sunﬂower oil or polyethylene glycol 300 as potential carriers.In a laboratory study,common voles were offered the bait and blood samples were collected 1,7,and 14 days after consumption.The samples were analyzed with LC-ESI-MS/MS for blood residues of Et-IPA.Sunﬂower-oil was the most suitable bait carrier.Et-IPA seemed to be palatable to common voles at all test concentrations.Dose-dependent residues could be detected in blood samples in a dose-dependent manner and up to 14 days after uptake enabling generation of a calibration curve of the dose-residue relationship.Et-IPA was present in common vole blood for at least 14 days,but there was dissipation by 33–37%depending on dose.Et-IPA meets many criteria for an“ideal”quantitative bait marker for use in futureﬁeld studies on common voles and possibly other small mammal species.

关键词： baiting biomarker Microtus arvalis quantitative bait marker small mammals

Rewiring regulation on respiro-fermentative metabolism relieved Crabtree effects in Saccharomyces cerevisiae

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Synthetic and Systems Biotechnology 2022年第4期7卷 1034-1043页

作者： Yiming Zhang Mo Su Zheng Wang jens nielsen Zihe Liu Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Life Science and TechnologyBeijing University of Chemical Technology100029BeijingChina Bloomage Biotechnolgy CO LTD250000JinanChina Department of Biology and Biological Engineering Chalmers University of TechnologySE296GothenburgSweden BioInnovation Institute Ole Maaløes Vej 3DK2200Copenhagen NDenmark

The respiro-fermentative metabolism in the yeast Saccharomyces cerevisiae,also called the Crabtree effect,results in lower energy efficiency and biomass yield which can impact yields of chemicals to be produced using this cell factory.Although it can be engineered to become Crabtree negative,the slow growth and glucose consumption rate limit its industrial application.Here the Crabtree effect in yeast can be alleviated by engineering the transcription factor Mth1 involved in glucose signaling and a subunit of the RNA polymerase II mediator complex Med2.It was found that the mutant with the MTH1A81D&MED2*432Y allele could grow in glucose rich medium with a specific growth rate of 0.30 h^(-1),an ethanol yield of 0.10 g g^(-1),and a biomass yield of 0.21 g g^(-1),compared with a specific growth rate of 0.40 h^(-1),an ethanol yield of 0.46 g g^(-1),and a biomass yield of 0.11 g g^(-1) in the wild-type strain CEN.PK 113-5D.Transcriptome analysis revealed significant downregulation of the glycolytic process,as well as the upregulation of the TCA cycle and the electron transfer chain.Significant expression changes of several reporter transcription factors were also identified,which might explain the higher energy efficiencies in the engineered strain.We further demonstrated the potential of the engineered strain with the production of 3-hydroxypropionic acid at a titer of 2.04 g L^(-1),i.e.,5.4-fold higher than that of a reference strain,indicating that the alleviated glucose repression could enhance the supply of mitochondrial acetyl-CoA.These results suggested that the engineered strain could be used as an efficient cell factory for mitochondrial production of acetyl-CoA derived chemicals.

关键词： Respiro-fermentation Crabtree effect Saccharomyces cerevisiae 3-Hydroxypropionic acid