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Caecal pH is a biomarker of excessive colonic fermentation

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World Journal of Gastroenterology 2014年第17期20卷 5000-5007页

作者： adam D farmer Sahar D Mohammed George E Dukes S Mark Scott Anthony R Hobson Centre for Digestive Diseases Blizard Institute of Cell and Molecular ScienceWingate Institute of NeurogastroenterologyBarts and the London School of Medicine and DentistryQueen Mary University of LondonLondon E1 2AJUnited Kingdom GlaxoSmithKline Research and Development Durham County NC 27709-3398United States Functional Gut Clinic London W1G 6NBUnited Kingdom

AIM: To ascertain whether caecal pH is different in patients with irritable bowel syndrome (IBS), whose primary symptoms are bloating and distension, to healthy controls.

关键词： Caecal pH Caecoparesis Bloating Colonic microbiota Fermentation

Assessment of the cardiovascular and gastrointestinal autonomic complications of diabetes

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World Journal of Diabetes 2016年第16期7卷 321-332页

作者： Christina Brock Birgitte Brock Anne Grave Pedersen Asbjorn Mohr Drewes Niels Jessen adam D farmer Mech-Sense Department of Gastroenterology and Hepatology Aalborg University Hospital DK-9000 AalborgDenmark Department of Pharmacotherapy and Development University of Copenhagen DK-2450 CopenhagenDenmark Clinical Biochemistry Aarhus University DK-3780 Aarhus Denmark Department of Clinical Medicine Aarhus UniversityDK-3780 Aarhus Denmark Department of Gastroenterology University Hospitals of North Midlands Staffordshire WS73 JQ United Kingdom Centre for Digestive Diseases Wingate Institute of Neurogastroenterology Blizard Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London EN1 1NX United Kingdom 不详

The global prevalence of diabetes mellitus is increasing; arguably as a consequence of changes in diet, lifestyle and the trend towards urbanization. Unsurprisingly, the incidence of both micro and macrovascular complications of diabetes mirrors this increasing prevalence. Amongst the complications with the highest symptom burden, yet frequently under-diagnosed and sub-optimally treated, is diabetic autonomic neuropathy, itself potentially resulting in cardiovascular autonomic neuropathy and gastrointestinal(GI) tract dysmotility. The aims of this review are fourfold. Firstly to provide an overview of the pathophysiological processes that cause diabetic autonomic neuropathy. Secondly, to discuss both the established and emerging cardiometric methods for evaluating autonomic nervous system function in vivo. Thirdly, to examine the tools for assessing pan-GI and segmental motility and finally, we will provide the reader with a summary of putative non-invasive biomarkers that provide a pathophysiological link between lowgrade neuro inflammation and diabetes, which may allow earlier diagnosis and intervention, which in future may improve patient outcomes.

关键词： Autonomic nervous system Gastrointestinal dysmotility Neuroinflammation Biomarkers Diabetic neuropathy

Brain changes in diabetes mellitus patients withgastrointestinal symptoms

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World Journal of Diabetes 2016年第2期7卷 14-26页

作者： Anne M Drewes Eirik Søfteland Georg Dimcevski adam D farmer Christina Brock Jens B Frøkjær Klaus Krogh Asbjørn M Drewes Department of Medicine Haukeland University Hospital5021 BergenNorway Centre for Digestive Diseases Blizard Institute of Cell and Molecular ScienceWingate Institute of NeurogastroenterologyBarts and the London School of Medicine and DentistryQueen Mary University of LondonLondon E1 2AJUnited Kingdom Department of Gastroenterology University Hospitals of North MidlandsStoke on TrentStraffordshire ST4 6QGUnited Kingdom Mech-Sense Department of Gastroenterology and Hepatology and Clinical InstituteAalborg University Hospital9100 AalborgDenmark Department of Radiology Aalborg University Hospital9100 AalborgDenmark Neurogastroenterology Unit Department of Hepatology and GastroenterologyAarhus University Hospital8000 AarhusDenmark

Diabetes mellitus is a common disease and its prevalence is increasing worldwide. In various studies up to 30%-70% of patients present dysfunction and complications related to the gut. To date several clinical studies have demonstrated that autonomic nervous system neuropathy and generalized neuropathy of the central nervous system(CNS) may play a major role. This systematic review provides an overview of the neurodegenerative changes that occur as a consequence of diabetes with a focus on the CNS changes and gastrointestinal(GI) dysfunction. Animal models where diabetes was induced experimentally support that the disease induces changes in CNS. Recent investigations with electroencephalography and functional brain imaging in patients with diabetes confirm these structural and functional brain changes. Encephalographic studies demonstrated that altered insular processing of sensory stimuli seems to be a key player in symptom generation. In fact one study indicated that the more GI symptoms the patients experienced, the deeper the insular electrical source was located. The electroencephalography was often used in combination with quantitative sensory testingmainly showing hyposensitivity to stimulation of GI organs. Imaging studies on patients with diabetes and GI symptoms mainly showed microstructural changes,especially in brain areas involved in visceral sensory processing. As the electrophysiological and imaging changes were associated with GI and autonomic symptoms they may represent a future therapeutic target for treating diabetics either pharmacologically or with neuromodulation.

关键词： Diabetes mellitus Gastrointestinal Electroencephalogram Magnetic resonance imaging Brain

Single-nucleus RNA and ATAC sequencing reveals the impact of chromatin accessibility on gene expression in Arabidopsis roots at the singlecell level

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Molecular Plant 2021年第3期14卷 372-383页

作者： Andrew farmer Sandra Thibivilliers Kook Hui Ryu John Schiefelbein Marc Libault National Center for Genome Resources Santa FeNM 87505USA Department of Agronomy and Horticulture Center for Plant Science InnovationUniversity of Nebraska-LincolnBeadle CenterLincolnNE 68503USA Department of Molecular Cellularand Developmental BiologyUniversity of MichiganAnn ArborMI 48109USA

Similar to other complex organisms,plants consist of diverse and specialized cell *** gain of unique biological functions of these different cell types is the consequence of the establishment of cell-typespecific transcriptional *** a necessary step in gaining a deeper understanding of the regulatory mechanisms controlling plant gene expression,we report the use of single-nucleus RNA sequencing(sNucRNA-seq)and single-nucleus assay for transposase accessible chromatin sequencing(sNucATACseq)technologies on Arabidopsis *** comparison of our single-nucleus transcriptomes to the published protoplast transcriptomes validated the use of nuclei as biological entities to establish plant cell-type-specific ***,our sNucRNA-seq results uncovered the transcriptomes of additional cell subtypes not identified by single-cell *** to our transcriptomic approach,the sNucATAC-seq approach led to the distribution of the Arabidopsis nuclei into distinct clusters,suggesting the differential accessibility of chromatin between groups of cells according to their *** reveal the impact of chromatin accessibility on gene expression,we integrated sNucRNA-seq and sNucATAC-seq data and demonstrated that cell-type-specific marker genes display cell-type-specific patterns of chromatin *** data suggest that the differential chromatin accessibility is a critical mechanism to regulate gene activity at the cell-type level.

关键词： single-cell RNA-seq single-nucleus ATAC-seq Arabidopsis root

Emerging Jasmonate Transporters

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Molecular Plant 2017年第5期10卷 659-661页

作者： Chi Tam Nguyen Enrico Martinoia Edward E. farmer Department of Plant Molecular Biology Biophore University of Lausanne 1015 Lausanne Switzerland Department of Plant and Microbial Biology University of Zurich Zollikerstrasse 107 8008 Zurich Switzerland

Jasmonic acid （JA） and methyl jasmonate （MeJA） are highly mobile and, when applied to intact plants,, these compounds powerfully modulate gene expression. Moreover, activation of jasmonate-responsive genes usually occurs in tissues distal to the treatments. It therefore comes as no surprise that there are jasmonate transporters; these proteins are only now emerging and their discovery is important for a number of reasons. Firstlv.

关键词： Emerging Jasmonate Transporters

The lattice Boltzmann Peierls Callaway equation for mesoscopic thermal transport modeling

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International Journal of Smart and Nano Materials 2012年第1期3卷 47-63页

作者： Jonghoon Lee Sangwook Sihn Ajit K.Roy Barry L.farmer Thermal Sciences and Materials Branch Materials and Manufacturing DirectorateAir Force Research LaboratoryWright Patterson Air Force BaseOhio 45433USA Universal Technology Corporation 1270 N.Fairfield Rd.DaytonOH 45432USA University of Dayton Research Institute 300 College ParkDaytonOhio 45469USA Materials and Manufacturing Directorate Air Force Research LaboratoryWright Patterson Air Force BaseOhio 45433USA

The lattice Boltzmann Peierls Callaway(LBPC)method is a recent development of the versatile lattice Boltzmann formalism aimed at a numerical experiment on mesoscale thermal transport in a multiphase phonon *** aspects of mesoscopic thermal trans-port are discussed:the finite phonon mean free path and the interface thermal *** on the phonon momentum screening length measured in the LBPC computa-tional apparatus,the validity of the Umklapp collision relaxation time in the Callaway collision operator is examined *** discrete nature of the spatio-temporal domain in the LBPC method,along with the linear approximation of the exponential screening mechanism in the Callaway operator,reveals a large discrepancy between the effective phonon mean free path and the analytic phonon mean free path when the relaxation time is *** link bounce back interface phonon collision rule is used to realize the interface thermal resistance between phonon gases with dissimilar dispersion *** with the Callaway collision operator for the bulk phonon dynam-ics,the interface phonon collision process is regarded as a linear relaxation mechanism toward the local pseudo-equilibrium phonon distribution uniquely defined by the energy conservation *** interface thermal resistance is linearly proportional to the relaxation time of the proposed phonon interface collision rule.

关键词： lattice Boltzmann method link bounce back collision rule Boltzmann Peierls equation phonon hydrodynamics Kapitza length interfacial thermal resistance

Clonal isolation of endothelial colony-forming cells from early gestation chorionic villi of human placenta for fetal tissue regeneration

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World Journal of Stem Cells 2020年第2期12卷 123-138页

作者： Kewa Gao Siqi He Priyadarsini Kumar Diana farmer Jianda Zhou Aijun Wang Department of Burns and Plastic Surgery The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina Surgical Bioengineering Laboratory Department of SurgeryUniversity of California DavisSacramentoCA 95817United States Institute for Pediatric Regenerative Medicine Shriners Hospitals for ChildrenSacramentoCA 95817United States Department of Biomedical Engineering University of California DavisDavisCA 95817United States

BACKGROUND Endothelial colony-forming cells(ECFCs)have been implicated in the process of vascularization,which includes vasculogenesis and *** is a de novo formation of blood vessels,and is an essential physiological process that occurs during embryonic development and tissue *** is the growth of new capillaries from pre-existing blood vessels,which is observed both prenatally and *** placenta is an organ composed of a variety of fetal-derived cells,including ECFCs,and therefore has significant potential as a source of fetal ECFCs for tissue *** To investigate the possibility of isolating clonal ECFCs from human early gestation chorionic villi(CV-ECFCs)of the placenta,and assess their potential for tissue *** The early gestation chorionic villus tissue was dissociated by enzyme *** expressing CD31 were selected using magnetic-activated cell sorting,and plated in endothelial-specific growth *** 2-3 wks in culture,colonies displaying cobblestone-like morphology were manually picked using cloning *** characterized CV-ECFCs by flow cytometry,immunophenotyping,tube formation assay,and Dil-Ac-LDL uptake *** transduction of CVECFCs was performed using a Luciferase/tdTomato-containing lentiviral vector,and transduction efficiency was tested by fluorescent microscopy and flow *** of CV-ECFCs with a delivery vehicle was determined using an FDA approved,small intestinal submucosa extracellular matrix *** After four passages in 6-8 wks of culture,we obtained a total number of 1.8×107 CV-ECFCs using 100 mg of early gestational chorionic villus *** analyses by flow cytometry demonstrated that CV-ECFCs highly expressed the endothelial markers CD31,CD144,CD146,CD105,CD309,only partially expressed CD34,and did not express CD45 and ***-ECFCs were capable of acetylated low-density lipoprotein uptake and tub

关键词： Placenta Endothelial colony forming cells Chorionic villi Angiogenesis Tissue engineering

Cell-specific pathways recruited for symbiotic nodulation in the Medicago truncatula legume

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Molecular Plant 2022年第12期15卷 1868-1888页

作者： Sergio Alan Cervantes-Pérez Sandra Thibivilliers Carole Laffont Andrew D.farmer Florian Frugier Marc Libault Department of Agronomy and Horticulture Center for Plant Science InnovationUniversity of Nebraska-LincolnLincolnNE 68503USA Single Cell Genomics Core Facility Center for BiotechnologyUniversity of Nebraska-LincolnLincolnNE 68588USA Institute of Plant Sciences Paris-Saclay(IPS2) UniversitéParis-SaclayCNRSINRAEUniversitéParis-CitéUniversitéd’Evry91190 Gif-sur-YvetteFrance National Center for Genome Resources Santa FeNM 87505USA

Medicago truncatula is a model legume species that has been studied for decades to understand the symbiotic relationship between legumes and soil bacteria collectively named *** symbiosis called nodulation is initiated in roots with the infection of root hair cells by the bacteria,as well as the initiation of nodule primordia from root cortical,endodermal,and pericycle cells,leading to the development of a new root organ,the nodule,where bacteria fix and assimilate the atmospheric dinitrogen for the benefit of the ***,we report the isolation and use of the nuclei from mock and rhizobia-inoculated roots for the single nuclei RNA-seq(sNucRNA-seq)profiling to gain a deeper understanding of early responses to rhizobial infection in Medicago roots.A gene expression map of the Medicago root was generated,comprising 25 clusters,which were annotated as specific cell types using 119 Medicago marker genes and orthologs to Arabidopsis cell-type marker genes.A focus on root hair,cortex,endodermis,and pericycle cell types,showing the strongest differential regulation in response to a short-term(48 h)rhizobium inoculation,revealed not only known genes and functional pathways,validating the sNucRNA-seq approach,but also numerous novel genes and pathways,allowing a comprehensive analysis of early root symbiotic responses at a cell type-specific level.

关键词： Medicago root single-cell transcriptomic rhizobium nodule initiation root hair cells cortical cells

Resilient and Inclusive Prosperity within Planetary Boundaries

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China & World Economy 2014年第5期22卷 76-92页

作者： Cameron Hepburn Eric Beinhocker J.Doyne farmer Alexander Teytelboym Institute for New Economic Thinking at Oxford Martin School the Smith School of Enterprise and the Environment University of Oxford the Grantham Research Institute at the London School of Economics and Political Science Institute for New Economic Thinking at the Oxford Martin School Blavatnik School of Government University of Oxford Mathematical Institute University of Oxford University of Oxford Laboratory for Information and Decision Systems Massachusetts Institute of Technology

The current model of economic growth generated unprecedented increases in human wealth and prosperity during the 19th and 2Oth centuries. The main mechanisms have been the rapid pace of technological and social innovation, human capital accumulation, and the conversion of resources and natural capital into more valuable forms of produced capital. However, there is evidence emerging that this model may be approaching environmental limits and planetary boundaries, and that the conversion of natural capital needs to slow down rapidly and then be reversed Some commentators have asserted that in order for this to occur, we will need to stop growing altogether and, instead, seek prosperity without growth. Others argue that environmental concerns are low-priority luxuries to be contemplated once global growth has properly returned to levels observed prior to the 2008 financial crisis. A third group argues that there is no trade-off and, instead,, promotes green growth： the （politically appealing） idea is that we can simultaneously grow and address our environmental problems. This paper provides a critical perspective on this debate and suggests that asubstantial researc＇h agenda is required to come to grips with these challenges. One place to start is with the relevant metrics： measures of per-capitawealth, and, eventually, quantitative measures of prosperity, alongside a dashboard of other sustainability indicators. A public andpoliticalfocus on wealth （a stock）, and its annual changes, could realistically complement the current focus on market-based gross output as measured by GDP （a flow）. This could have important policy implications, but deeper changes to governance and business models will be required.

关键词： green growth limits to growth planetary boundaries resilience sustainable prosperity