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The future of genome-scale modeling of yeast through integration of a transcriptional regulatory network

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Frontiers of Electrical and Electronic Engineering in China 2014年第1期9卷 30-46页

作者： Guodong Liu Antonio Marras Jens nielsen Novo Nordisk Foundation Center for Biosustainability Department of Chemical and Biological Engineering Chalmers University of Technology Gothenburg SE41296 Sweden Novo Nordisk Foundation Center for Biosustainability Technical University of Denmark Hфrsholm DK2970 Denmark

Metabolism is regulated at multiple levels in response to the changes of internal or external conditions. Transcriptional regulation plays an important role in regulating many metabolic reactions by altering the concentrations of metabolic enzymes. Thus, integration of the transcriptional regulatory information is necessary to improve the accuracy and predictive ability of metabolic models. Here we review the strategies for the reconstruction of a transcriptional regulatory network （TRN） for yeast and the integration of such a reconstruction into a flux balance analysis-based metabolic model. While many large-scale TRN reconstructions have been reported for yeast, these reconstructions still need to be improved regarding the functionality and dynamic property of the regulatory interactions. In addition, mathematical modeling approaches need to be further developed to efficiently integrate transcriptional regulatory interactions to genome-scale metabolic models in a quantitative manner.

关键词： transcriptional regulatory network metabolic model saccharomyces cerevisiae integration

sensory testing of the human gastrointestinal tract

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World Journal of Gastroenterology 2009年第2期15卷 151-159页

作者： Christina Brock Lars Arendt-nielsen Oliver Wilder-smith Asbjφrn Mohr Drewes Mech-sense Department of Gastroenterology Aalborg Hospital DK-9000 Aalborg Denmark Center for sensory-Motor Interactions Department of Health Science and Technology Aalborg University DK-9000 Aalborg Denmark Pain and Nociception Research Group Department of Anaesthesiology Radboud University Nijmegen Medical Centrethe Netherlands Mech-sense Department of Gastro-enterology Aalborg Hospital DK-9000 Aalborg Denmark Author

The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm （single, train, tetanic） influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation （cold or warm） activates selectively mucosal receptors, and chemical substances such as acid and capsaicin （either alone or in combination） are used to evoke pain and sensitization. The possibility of multimodal （e.g. mechanical, electrical, thermal and chemical） stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to dinicians

关键词： Endoscopy Intestine Experimental Neurophysiology Pain

Investigation on balcony plume entrainment

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Journal of Central south University 2009年第S1期16卷 105-110页

作者：刘方 nielsen P V HEILsELBERG P BROHUs H Faculty of Urban Construction and Environment Engineering Chongqing University Department of Civil Engineering Aalborg University

An investigation on the scenarios of the spill plume and its equation was presented,including two aspects,i.e.,the small-scale experiment and the numerical simulation. Two balcony spill plume models are assessed by comparing with the fire dynamic simulation (FDs) and small scale model experiment results. Besides validating the spill model by experiments,the effect of different fire locations on balcony plume is also discussed. The results show that the balcony equation in NFPA gives good predictions on the mass flow rate. And the balcony plume entrainment coefficient is independent of the fire location. This investigation is useful for the fire engineers in designing smoke control systems.

关键词： fire plume entrainment atrium

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 *** it can be engineered to become Crabtree negative,the slow growth and glucose consumption rate limit its industrial *** 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 *** 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 *** *** analysis revealed significant downregulation of the glycolytic process,as well as the upregulation of the TCA cycle and the electron transfer *** expression changes of several reporter transcription factors were also identified,which might explain the higher energy efficiencies in the engineered *** 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 *** 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

The impact of genotyping strategies and statistical models on accuracy of genomic prediction for survival in pigs

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Journal of Animal science and Biotechnology 2023年第3期14卷 908-916页

作者： Tianfei Liu Bjarne nielsen Ole F.Christensen Mogens sandøLund Guosheng su Institute of Animal science Guangdong Academy of Agricultural SciencesGuangzhou 510640China Center for Quantitative Genetics and Genomics Aarhus University8830 TjeleDenmark Pig Research Centre SEGES1609 CopenhagenDenmark

Background:survival from birth to slaughter is an important economic trait in commercial pig *** survival can improve both economic efficiency and animal *** aim of this study is to explore the impact of genotyping strategies and statistical models on the accuracy of genomic prediction for survival in pigs during the total growing period from birth to ***:We simulated pig populations with different direct and maternal heritabilities and used a linear mixed model,a logit model,and a probit model to predict genomic breeding values of pig survival based on data of individual survival records with binary outcomes(0,1).The results show that in the case of only alive animals having genotype data,unbiased genomic predictions can be achieved when using variances estimated from pedigreebased *** using genomic information achieved up to 59.2%higher accuracy of estimated breeding value compared to pedigree-based model,dependent on genotyping *** scenario of genotyping all individuals,both dead and alive individuals,obtained the highest *** an equal number of individuals(80%)were genotyped,random sample of individuals with genotypes achieved higher accuracy than only alive individuals with *** linear model,logit model and probit model achieved similar ***:Our conclusion is that genomic prediction of pig survival is feasible in the situation that only alive pigs have genotypes,but genomic information of dead individuals can increase accuracy of genomic prediction by 2.06%to 6.04%.

关键词： Genomic prediction Genotyping strategy simulation statistical models survival

Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

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World Journal of Gastroenterology 2006年第18期12卷 2805-2817页

作者： Asbjφrn Mohr Drewes Lars Arendt-nielsen Peter Funch-Jensen Hans Gregersen Center for Visceral Biomechanics and Pain Department of GastroenterologyAalborg Hospitaland Center for Sensory-Motor InteractionsDepartment of Health Science and TechnologyAalborg UniversityDenmark Department of surgical Gastroenterology L Aarhus HospitalDenmark

Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.

关键词： Pain Gut Experimental Chest pain Esophagitis

应用似然函数比以及Fourier变换计算置信度的解析方法(英文)

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高能物理与核物理 2000年第5期24卷 445-450页

作者：胡红波 Jason nielsen UniversityofWisconsinMadison

新粒子寻找的实验结果要通过计算置信度来解释 ,置信度的定义或是基于新粒子与本底并存的假设 ,或是基于唯有本底存在的假设 .通常的计算方法是产生大量的toyMonteCarlo实验 ,这些实验按照某种定义的估计值的大小以顺序排列 ,然后将真... 详细信息

新粒子寻找的实验结果要通过计算置信度来解释 ,置信度的定义或是基于新粒子与本底并存的假设 ,或是基于唯有本底存在的假设 .通常的计算方法是产生大量的toyMonteCarlo实验 ,这些实验按照某种定义的估计值的大小以顺序排列 ,然后将真正观测到的实验的估计值与之相比较 ,从而得到置信度 .本文则介绍一种新的计算方法 ,通过定义似然函数比为实验的估计值 ,并应用Fourier变换 ,用解析的方法计算出置信度 ,与toyMonteCarlo方法相比。

关键词：置信度 Fourier变换粒子似然函数比

Loss of mismatch repair signaling impairs the WNT–bone morphogenetic protein crosstalk and the colonic homeostasis

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Journal of Molecular Cell Biology 2020年第6期12卷 410-423页

作者： Katrine Nørgaard Carolin Müller Nadja Christensen María L.Chiloeches Cesilie L.Madsen sabine s.nielsen Tine E.Thingholm Antoaneta Belcheva Department of Biochemistry and Molecular Biology University of Southern DenmarkCampusvej 555230 Odense MDenmark Department of Molecular Medicine University of Southern DenmarkJ.B.Winsløws Vej 255230 Odense MDenmark

The fine balance between proliferation,differentiation,and apoptosis in the colonic epithelium is tightly controlled by the interplay between WNT,Notch,and bone morphogenetic protein(BMP)*** these complex networks coordinate the colonic homeostasis,especially if cancer predisposing mutations such as mutations in the DNA mismatch repair(MMR)are present,is *** of the MMR system has long been linked to colorectal cancer;however,little is known about its role in the regulation of the colonic *** has been shown that loss of MMR promotes the proliferation of colon epithelial cells that renders them highly susceptible to *** mechanism through which MMR mediates this effect,yet,remains to be *** an MMR-deficient mouse model,we show that increased methylation of Dickkopf1 impacts its expression,and consequently,the ability to negatively regulate WNT *** a result,excessive levels of activeβ-catenin promote strong crypt progenitor-like phenotype and abnormal *** these settings,the development and function of the goblet cells are ***-deficient mice have fewer goblet cells with enlarged mucin-loaded *** further show that MMR inactivation impacts the WNT–BMP signaling crosstalk.

关键词： MMR colonic epithelium WNT BMP crypt homeostasis

Ultrasonographic study of mechanosensory properties in human esophagus during mechanical distension

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World Journal of Gastroenterology 2006年第28期12卷 4517-4523页

作者： Ejnar Larsen Hariprasad Reddy AsbjΦrn Mohr Drewes Lars Arendt-nielsen Hans Gregersen Department of Radiology Aalborg HospitalAalborg DK-9100Denmark Center for Visceral Biomechanics and Pain Aalborg HospitalAalborg DK-9100Denmark Laboratory for Experimental Pain Research Center for Sensory-Motor InteractionDepartment of Health TechnologyAalborg UniversityAalborg Dk-9100Denmark

TIM： To study the esophageal geometry and mechanosensation using endoscopic ultrasonography during volume-controlled ramp distensions in the distal esophagus. METHODs： Twelve healthy volunteers underwent distension of a bag. During distension up to moderate pain the sensory intensity was assessed on a visual analogue scale （VAs）. The esophageal deformation in terms of multidimensional stretch ratios and strains was calculated at different volumes and VAs levels. Distensions were done before and during administration of the anticholinergic drug butylscopolamine. REsULTs： The stimulus-response （volume-VAs） curve did not differ without or with the administration of butylscopolamine. Analysis of stretch ratios demonstrated tensile stretch in circumferential direction, compression in radial direction and a small tensile stretch in longitudinal direction. A strain gradient existed throughout the esophageal wall with the largest circumferential deformation at the mucosal surface. The sensation intensity increased exponentially as function of the strains. CONCLUsION： The method provides information of esophageal deformation gradients that correlate to the sensation intensity. Hence, it can be used to study mechanosensation in the human esophagus. Further studies are needed to determine the exact deformation stimulus for the esophageal mechanoreceptors.

关键词： Deformation analysis Esophagus Experimental pain Ultrasonography