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  • 151. Turkina, Maria V
    et al.
    Villarejo, Arsenio
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Vener, Alexander V
    The transit peptide of CP29 thylakoid protein in Chlamydomonas reinhardtii is not removed but undergoes acetylation and phosphorylation2004In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 564, no 1-2, p. 104-108Article in journal (Refereed)
    Abstract [en]

    The surface-exposed peptides were cleaved by trypsin from the photosynthetic thylakoid membranes isolated from the green alga Chlamydomonas reinhardtii. Two phosphorylated peptides, enriched from the peptide mixture and sequenced by nanospray quadrupole time-of-flight mass spectrometry, revealed overlapping sequences corresponding to the N-terminus of a nuclear-encoded chlorophyll a/b-binding protein CP29. In contrast to all known nuclear-encoded thylakoid proteins, the transit peptide in the mature algal CP29 was not removed but processed by methionine excision, N-terminal acetylation and phosphorylation on threonine 6. The importance of this phosphorylation site is proposed as the reason of the unique transit peptide retention.

  • 152. Valerio, M
    et al.
    Haraux, F
    Gardeström, Per
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Diolez, P
    Tissue-specificity of the regulation of ATP hydrolysis by isolated plant-mitochondria1993In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 318, no 2, p. 113-117Article in journal (Refereed)
    Abstract [en]

    Pea leaf mitochondria had a high ATP hydrolase activity following the collapse of the membrane potential by addition of valinomycin in state 4. In mitochondria isolated from potato tubers such ATP hydrolase activity was not observed. Pea leaf mitochondria also had a DELTApH, in contrast to what was previously found for potato tuber mitochondria. This DELTApH could, however, not explain the different results on ATP hydrolysis since this activity was also observed in the presence of nigericin. The results suggest a tissue-specific regulation of ATP hydrolysis in resting organs (potato tubers) as compared to active organs (leaves).

  • 153.
    Vdovikova, Svitlana
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Gilfillan, Siv
    Wang, Shixiong
    Dongre, Mitesh
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Hurtado, Antonio
    Modulation of gene transcription and epigenetics of colon carcinoma cells by bacterial membrane vesicles2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 7434Article in journal (Refereed)
    Abstract [en]

    Interactions between bacteria and colon cancer cells infuence the transcription of the host cell. Yet is it undetermined whether the bacteria itself or the communication between the host and bacteria is responsible for the genomic changes in the eukaryotic cell. Now, we have investigated the genomic and epigenetic consequences of co-culturing colorectal carcinoma cells with membrane vesicles from pathogenic bacteria Vibrio cholerae and non-pathogenic commensal bacteria Escherichia coli. Our study reveals that membrane vesicles from pathogenic and commensal bacteria have a global impact on the gene expression of colon-carcinoma cells. The changes in gene expression correlate positively with both epigenetic changes and chromatin accessibility of promoters at transcription start sites of genes induced by both types of membrane vesicles. Moreover, we have demonstrated that membrane vesicles obtained only from V. cholerae induced the expression of genes associated with epithelial cell diferentiation. Altogether, our study suggests that the observed genomic changes in host cells might be due to specifc components of membrane vesicles and do not require communication by direct contact with the bacteria.

  • 154. Vera-Sirera, Francisco
    et al.
    De Rybel, Bert
    Urbez, Cristina
    Kouklas, Evangelos
    Pesquera, Marta
    Camilo Alvarez-Mahecha, Juan
    Minguet, Eugenio G.
    Tuominen, Hannele
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Carbonell, Juan
    Borst, Jan Willem
    Weijers, Dolf
    Blazquez, Miguel A.
    A bHLH-Based Feedback Loop Restricts Vascular Cell Proliferation in Plants2015In: Developmental Cell, ISSN 1534-5807, E-ISSN 1878-1551, Vol. 35, no 4, p. 432-443Article in journal (Refereed)
    Abstract [en]

    Control of tissue dimensions in multicellular organisms requires the precise quantitative regulation of mitotic activity. In plants, where cells are immobile, tissue size is achieved through control of both cell division orientation and mitotic rate. The bHLH transcription factor heterodimer formed by TARGET OF MONOPTEROS5 (TMO5) and LONESOME HIGHWAY (LHVV) is a central regulator of vascular width-increasing divisions. An important unanswered question is how its activity is limited to specify vascular tissue dimensions. Here we identify a regulatory network that restricts TMO5/LHW activity. We show that thermospermine synthase ACAULIS5 antagonizes TMO5/LHW activity by promoting the accumulation of SAC51-LIKE (SACL) bHLH transcription factors. SACL proteins heterodimerize with LHW therefore likely competing with TMO5/LHW interactions prevent activation of TMO5/LHW target genes, and suppress the over-proliferation caused by excess TMO5/LHW activity. These findings connect two thus-far disparate pathways and provide a mechanistic understanding of the quantitative control of vascular tissue growth.

  • 155.
    Vidal-Quadras, Maite
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Holst, Mikkel R.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Francis, Monika K.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Peränen, Johan
    Lundmark, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Endocytic turnover of Rab8 controls cell polarisationManuscript (preprint) (Other academic)
  • 156.
    Viotti, Corrado
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). University of Heidelberg, Germany.
    Krüger, Falco
    Neubert, Christoph
    Fink, Fabian
    Lupanga, Upendo
    Krebs, Melanie
    Scheuring, David
    Hemsley, Piers A.
    Boutté, Yohann
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Frescatada-Rosa, Márcia
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Wolfenstetter, Susanne
    Sauer, Norbert
    Hillmer, Stefan
    Grebe, Marcus
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Schumacher, Karin
    The Endoplasmic Reticulum Is the Main Membrane Source for Biogenesis of the Lytic Vacuole in Arabidopsis2013In: The Plant Cell, ISSN 1040-4651, E-ISSN 1532-298X, Vol. 25, no 9, p. 3434-3449Article in journal (Refereed)
    Abstract [en]

    Vacuoles are multifunctional organelles essential for the sessile lifestyle of plants. Despite their central functions in cell growth, storage, and detoxification, knowledge about mechanisms underlying their biogenesis and associated protein trafficking pathways remains limited. Here, we show that in meristematic cells of the Arabidopsis thaliana root, biogenesis of vacuoles as well as the trafficking of sterols and of two major tonoplast proteins, the vacuolar H+-pyrophosphatase and the vacuolar H+-adenosinetriphosphatase, occurs independently of endoplasmic reticulum (ER)-Golgi and post-Golgi trafficking. Instead, both pumps are found in provacuoles that structurally resemble autophagosomes but are not formed by the core autophagy machinery. Taken together, our results suggest that vacuole biogenesis and trafficking of tonoplast proteins and lipids can occur directly from the ER independent of Golgi function.

  • 157.
    Wang, Sen
    et al.
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi, China.
    Zhao, Guanghui
    Xi'an Honghui Hospital, Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Shao, Wanzhen
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi, China.
    Liu, Huan
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi, China.
    Wang, Weizhuo
    Orthopedic Department, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Wu, Cuiyan
    Orthopedic Department, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi, China; School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
    Guo, Xiong
    Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi, China; School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
    The importance of Se-related genes in the chondrocyte of Kashin-Beck disease revealed by whole genomic microarray and network analysis2019In: Biological Trace Element Research, ISSN 0163-4984, E-ISSN 1559-0720, Vol. 187, no 2, p. 367-375Article in journal (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD) is an endemic, chronic, and degenerative osteoarthropathy. Selenium (Se) deficiency plays important role in the pathogenesis of KBD. We aimed to screen Se-related gene from chondrocytes of patients with KBD. Whole-genome oligonucleotide microarrays were used to detect differentially expressed genes. qRT-PCR was used to confirm the microarray results. Comparative Toxicogenomics Database (CTD) was used to screen Se-related genes from differentially expressed genes. Gene Ontology (GO) classifications and network analysis of Se-related genes were constituted by STRING online system. Three hundred ninety-nine differentially expressed genes were obtained from microarray. Among them, 54 Se-related genes were identified by CTD. The qRT-PCR validation showed that four genes expressed similarly with the ones in the microarray transcriptional profiles. The Se-related genes were categorized into 6 cellular components, 8 molecular functions, 44 biological processes, 10 pathways, and 1 network by STRING. The Se-related gene insulin-like growth factor binding protein 2 (IGFBP2), insulin-like growth factor binding protein 3 (IGFBP3), interleukin 6 (IL6), BCL2, apoptosis regulator (BCL2), and BCL2-associated X, apoptosis regulator (BAX), which involved in many molecular functions, biological processes, and apoptosis pathway may play important roles in the pathogenesis of KBD.

  • 158.
    Wang, Wei-Zhou
    et al.
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China; Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Guo, Xiong
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Duan, Chen
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Ma, Wei Juan
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Zhang, Y G
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Xu, P
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Gao, Z Q
    Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Wang, Z F
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Yan, H
    National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi'an, China.
    Zhang, Y F
    National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi'an, China.
    Yu, Y X
    Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, China.
    Chen, J C
    Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Comparative analysis of gene expression profiles between the normal human cartilage and the one with endemic osteoarthritis.2009In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 17, no 1, p. 83-90, article id 18579416Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the differences in gene expression profiles of adult articular cartilage with endemic osteoarthritis (OA), Kashin-Beck disease (KBD), and the same regions in the normal joint.

    METHODS: The messenger RNA expression profiles of articular cartilage with KBD diagnosed according to "Diagnosing Criteria of Kashin-Beck Disease in China" were compared with the normal cartilage. Total RNA isolated separately from four pairs of the KBD and normal cartilage samples were evaluated by oligonucleotide microarray analysis. The microarray data were confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) amplification and were compared with previously published experiments.

    RESULTS: About 4100 transcripts, which corresponded to 35% of the expressed transcripts, showed >or=twofold differences in expression between the cartilage tissues in pairs. Approximately 2% of the expressed genes (79, 55 genes expressed in KBD>normal; 24 genes expressed in KBD<normal) were commonly expressed in the four pairs of samples. The expression of some genes related to the metabolism, apoptosis, cell proliferation and matrix degradation activity was significantly different in KBD cartilage than in the normal, similar to the findings for genes that inhibit matrix degradation. Comparisons of qRT-PCR data and the previously reported data with the result of gene chips support the validity of our microarray data.

    CONCLUSION: Differences between KBD cartilage and the normal exhibited a similar pattern among the four pairs examined, indicating the presence of common mechanisms mainly including chondrocyte metabolism and apoptosis that contribute to cartilage destruction in KBD.

  • 159. Wang, Xuefeng
    et al.
    Ohlin, Christian A.
    Lu, Qinghua
    Hu, Jun
    Cell directional migration and oriented division on three-dimensional laser-induced periodic surface structures on polystyrene2008In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 29, no 13, p. 2049-2059Article in journal (Refereed)
    Abstract [en]

    The extracellular matrix in animal tissues usually provides a three-dimensional structural support to cells in addition to performing various other important functions. In the present study, wavy submicrometer laser-irradiated periodic surface structures (LIPSS) were produced on a smooth polystyrene film by polarized laser irradiation with a wavelength of 266 nm. Rat C6 glioma cells exhibited directional migration and oriented division on laser-irradiated polystyrene, which was parallel to the direction of LIPSS. However, rat C6 glioma cells on smooth polystyrene moved in a three-step invasion cycle, with faster migation speed than that on laser-irradiated polystyrene. In addition, focal adhesions examined by immunostaining focal adhesion kinase in human epithelial carcinoma HeLa cells were punctuated on smooth polystyrene, whereas dash-like on laser-irradiated polystyrene. We hypothesized that LIPSS on laser-irradiated polystyrene acted as an anisotropic and persistent mechanical stimulus to guide cell anisotropic spreading, migration and division through focal adhesions.

  • 160.
    Wanrooij, Paulina H.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110.
    Tannous, Elias
    Kumar, Sandeep
    Navadgi-Patil, Vasundhara M.
    Burgers, Peter M.
    Probing the Mec1ATR Checkpoint Activation Mechanism with Small Peptides2016In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 1, p. 393-401Article in journal (Refereed)
    Abstract [en]

    Yeast Mec1, the ortholog of human ATR, is the apical protein kinase that initiates the cell cycle checkpoint in response to DNA damage and replication stress. The basal activity of Mec1 kinase is activated by cell cycle phase-specific activators. Three distinct activators stimulate Mec1 kinase using an intrinsically disordered domain of the protein. These are the Ddc1 subunit of the 9-1-1 checkpoint clamp (ortholog of human and Schizosaccharomyces pombe Rad9), the replication initiator Dpb11 (ortholog of human TopBP1 and S. pombe Cut5), and the multifunctional nuclease/helicase Dna2. Here, we use small peptides to determine the requirements for Mec1 activation. For Ddc1, we identify two essential aromatic amino acids in a hydrophobic environment that when fused together are proficient activators. Using this increased insight, we have been able to identify homologous motifs in S. pombe Rad9 that can activate Mec1. Furthermore, we show that a 9-amino acid Dna2-based peptide is sufficient for Mec1 activation. Studies with mutant activators suggest that binding of an activator to Mec1 is a two-step process, the first step involving the obligatory binding of essential aromatic amino acids to Mec1, followed by an enhancement in binding energy through interactions with neighboring sequences.

  • 161.
    Wessels, Bernard
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    The significance of ethylene and ETHYLENE RESPONSE FACTORS in wood formation of hybrid aspen2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The woody tissues serve to stabilise plants, store nutrients and translocate water and minerals. The formation of wood, or ’secondary xylem’, follows a well-defined developmental gradient which is initiated by cell division activity in the vascular cambium. The ’xylem cambial derivatives’ then expand before deposition of the secondary cell wall (SCW), which is where most of the biomass of wood originates. After this, some cells of the xylem typically undergo programmed cell death (PCD). Cellulose and lignin are chemical components of the SCW that provide structural support and water impermeability, respectively. The chemical composition of the SCWs is also important economically since it affects the efficiency of wood processing during pulping and enzymatic hydrolysis. Two dominant xylem cell types of angiosperm tree species like Populus are the fibers and the vessel elements. Fibers are important for the mechanical strength of the wood and provide the majority of the wood biomass. Vessel elements join endwise to form hollow tubes, or vessels, for the purposes of water and solute transport in the stem.

     

    Formation of wood is a complex process, subject to multiple levels of regulation. Plant hormones are important for wood formation, and ethylene signalling has been shown to stimulate cambial activity, affect the ratio between fibers and vessel elements, as well as the expansion of the cambial derivatives. Ethylene is also involved in the ‘tension wood’ response of stems that are displaced from their original vertical position. Formation of ’tension wood’ generates a force that lifts the stem back to the upright growing position. What remains unknown is the molecular link between ethylene signalling and wood formation. The work in this thesis focuses on providing this link using the model tree species hybrid aspen (Populus tremula x tremuloides).

     

    Using a state-of-the-art transcriptomic database that spans all phases of xylem differentiation in hybrid aspen wood, from cell division through xylem cell expansion to xylem maturation (SCW deposition and PCD), the expression of the ethylene pathway related genes was investigated during normal wood formation. The analyses reveal ethylene perception and transcriptional reprogramming is possible across all zones of wood formation. Previously uncharacterised components were identified that may be important contributors to wood formation. Furthermore, although ethylene is known to affect the ratio between the abundance of the vessel elements and the fibers, genetic evidence is lacking. Using the tension wood response and transgenic trees modified in ethylene signalling, it was shown that ethylene is a negative regulator of vessel formation and important for a functional tension wood response. Furthermore, characterisation of two transcription factors (TFs), belonging to the ethylene response factor (ERF) gene family, suggests that aspects of xylem cell division, expansion and subsequent SCW formation, including lignification, can be affected by ERF85 and ERF139 in an ethylene-dependent manner. Phase transitions during wood formation need to be controlled spatiotemporally, and transcriptional regulation by these ERFs seems to be part of such control to establish correct transitions between cell expansion, secondary cell wall formation and lignification. The work presented here also identifies promising additions to the toolkit available for forest tree biotechnology and molecular breeding programmes.

  • 162.
    Wieloch, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Intramolecular isotope analysis reveals plant ecophysiological signals covering multiple timescales2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Our societies' wellbeing relies on stable and healthy environments. However, our current lifestyles, growth-oriented economic policies and the population explosion are leading to potentially catastrophic degradation of ecosystems and progressive disruption of food chains. Hopefully, more clarity about what the future holds in store will trigger stronger efforts to find, and adopt, problem-focused coping strategies and encourage environmentally friendly lifestyles.

    Forecasting environmental change/destruction is complicated (inter alia) by lack of complete understanding of plant-environment interactions, particularly those involved in slow processes such as plant acclimatisation and adaptation. This stems from deficiencies in tools to analyse such slow processes. The present work aims at developing tools that can provide retrospective ecophysiological information covering timescales from days to millennia.

    Natural archives, such as tree-rings, preserve plant metabolites over long timescales. Analyses of intramolecular isotope abundances in plant metabolites have the potential to provide retrospective information about metabolic processes and underlying environmental controls. Thus, my colleagues and I (hereafter we) analysed intramolecular isotope patterns in tree rings to develop analytical tools that can convey information about clearly-defined plant metabolic processes over multiple timescales. Such tools might help (inter alia) to constrain plants' capacities to sequester excess amounts of anthropogenic CO2; the so-called CO2 fertilisation effect. This, in turn, might shed light on plants' sink strength for the greenhouse gas CO2, and future plant performance and growth under climate change.

    In the first of three studies, reported in appended papers, we analysed intramolecular 13C/12C ratios in tree-ring glucose. In six angiosperm and six gymnosperm species we found pronounced intramolecular 13C/12C differences, exceeding 10‰. These differences are transmitted into major global C pools, such as soil organic matter. Taking intramolecular 13C/12C differences into account might improve isotopic characterisation of soil metabolic processes and soil CO2 effluxes. In addition, we analysed intramolecular 13C/12C ratios in a Pinus nigra tree-ring archive spanning the period 1961 to 1995. These data revealed new ecophysiological 13C/12C signals, which can facilitate climate reconstructions and assessments of plant-environment interactions at higher resolution; thus providing higher quality information. We proposed that 13C/12C signals at glucose C-1 to C-2 derive from carbon injection into the Calvin-Benson cycle via the oxidative pentose phosphate pathway. We concluded that intramolecular 13C/12C measurements provide valuable new information about long-term metabolic dynamics for application in biogeochemistry, plant physiology, plant breeding, and paleoclimatology.

    In the second study, we developed a comprehensive theory on the metabolic and ecophysiological origins of 13C/12C signals at tree-ring glucose C-5 and C-6. According to this theory and theoretical implications of the first study on signals at C-1 to C-3, analysis of such intramolecular signals can provide information about several metabolic processes. At C-3, a well-known signal reflecting CO2 uptake is preserved. The glucose-6-phosphate shunt around the Calvin-Benson cycle affects 13C/12C compositions at C-1 and C-2, while the 13C/12C signals at C-5 and C-6 reflect carbon fluxes into downstream metabolism. This theoretical framework enables further experimental studies to be conducted in a hypothesis-driven manner. In conclusion, the intramolecular approach provides information about carbon allocation in plant leaves. Thus, it gives access to long-term information on key ecophysiological processes, which could not be acquired by previous approaches.

    The abundance of the hydrogen isotope deuterium, δD, is important for linking the water cycle with plant ecophysiology. The main factors affecting δD in plant organic matter are commonly assumed to be the δD in source water and leaf-level evaporative enrichment. Current δD models incorporate biochemical D fractionations as constants. In the third study we showed that biochemical D fractionations respond strongly to low ambient CO2 levels and low light intensity. Thus, models of δD values in plant organic matter should incorporate biochemical fractionations as variables. In addition, we found pronounced leaf-level δD differences between α-cellulose and wax n-alkanes. We explained this by metabolite-specific contributions of distinct hydrogen sources during biosynthesis.

    Overall, this work advances our understanding of isotope distributions and isotope fractionations in plants. It reveals the immense potential of intramolecular isotope analyses for retrospective assessment of plant metabolism and associated environmental controls.

  • 163.
    Wieloch, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sharkey, Thomas David
    Werner, Roland Anton
    Schleucher, Jürgen
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Intramolecular 13C/12C signals reflect carbon allocation in plant leavesManuscript (preprint) (Other academic)
  • 164. Williams, Jon P
    et al.
    Wu, Jianqiang
    Johansson, Gunnar
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University.
    Rizvi, Tilat A
    Miller, Shyra C
    Geiger, Hartmut
    Malik, Punam
    Li, Wenling
    Mukouyama, Yoh-suke
    Cancelas, Jose A
    Ratner, Nancy
    Nf1 mutation expands an EGFR-dependent peripheral nerve progenitor that confers neurofibroma tumorigenic potential.2008In: Cell stem cell, ISSN 1875-9777, Vol. 3, no 6, p. 658-69Article in journal (Refereed)
    Abstract [en]

    Defining growth factor requirements for progenitors facilitates their characterization and amplification. We characterize a peripheral nervous system embryonic dorsal root ganglion progenitor population using in vitro clonal sphere-formation assays. Cells differentiate into glial cells, smooth muscle/fibroblast (SM/Fb)-like cells, and neurons. Genetic and pharmacologic tools revealed that sphere formation requires signaling from the EGFR tyrosine kinase. Nf1 loss of function amplifies this progenitor pool, which becomes hypersensitive to growth factors and confers tumorigenesis. DhhCre;Nf1(fl/fl) mouse neurofibromas contain a progenitor population with similar growth requirements, potential, and marker expression. In humans, NF1 mutation predisposes to benign neurofibromas, incurable peripheral nerve tumors. Prospective identification of human EGFR(+);P75(+) neurofibroma cells enriched EGF-dependent sphere-forming cells. Neurofibroma spheres contain glial-like progenitors that differentiate into neurons and SM/Fb-like cells in vitro and form benign neurofibroma-like lesions in nude mice. We suggest that expansion of an EGFR-expressing early glial progenitor contributes to neurofibroma formation.

  • 165. Wood, Matthew
    et al.
    Rawe, Melissa
    Johansson, Gunnar
    Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital, University of Cincinnati College of Medicine.
    Pang, Shu
    Soderquist, Ryan S
    Patel, Ami V
    Nelson, Sandra
    Seibel, William
    Ratner, Nancy
    Sanchez, Yolanda
    Discovery of a small molecule targeting IRA2 deletion in budding yeast and neurofibromin loss in malignant peripheral nerve sheath tumor cells2011In: Molecular Cancer Therapeutics, ISSN 1535-7163, E-ISSN 1538-8514, Vol. 10, no 9, p. 1740-1750Article in journal (Refereed)
    Abstract [en]

    Malignant peripheral nerve sheath tumor (MPNST) is a life-threatening complication of neurofibromatosis type 1 (NF1). NF1 is caused by mutation in the gene encoding neurofibromin, a negative regulator of Ras signaling. There are no effective pharmacologic therapies for MPNST. To identify new therapeutic approaches targeting this dangerous malignancy, we developed assays in NF1(+/+) and NF1(-/-) MPNST cell lines and in budding yeast lacking the NF1 homologue IRA2 (ira2Δ). Here, we describe UC1, a small molecule that targets NF1(-/-) cell lines and ira2Δ budding yeast. By using yeast genetics, we identified NAB3 as a high-copy suppressor of UC1 sensitivity. NAB3 encodes an RNA binding protein that associates with the C-terminal domain of RNA Pol II and plays a role in the termination of nonpolyadenylated RNA transcripts. Strains with deletion of IRA2 are sensitive to genetic inactivation of NAB3, suggesting an interaction between Ras signaling and Nab3-dependent transcript termination. This work identifies a lead compound and a possible target pathway for NF1-associated MPNST, and shows a novel model system approach to identify and validate target pathways for cancer cells in which NF1 loss drives tumor formation.

  • 166.
    Wu, Jungfang
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Zivkovic, Angela M
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Oxylipins, endocannabinoids, and related compounds in human milk: levels and effects of storage conditions2016In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 122, p. 28-36Article in journal (Refereed)
    Abstract [en]

    The presence of fatty acid derived oxylipins, endocannabinoids and related compounds in human milk may be of importance to the infant. Presently, clinically relevant protocols for storing and handling human milk that minimize error and variability in oxylipin and endocannabinoid concentrations are lacking. In this study, we compared the individual and combined effects of the following storage conditions on the stability of these fatty acid metabolites in human milk: state (fresh or frozen), storage temperature (4 °C, -20 °C or -80 °C), and duration (1 day, 1 week or 3 months). Thirteen endocannabinoids and related compounds, as well as 37 oxylipins were analyzed simultaneously by liquid chromatography coupled to tandem mass spectrometry. Twelve endocannabinoids and related compounds (2–111 nM) and 31 oxylipins (1.2 pM–1242 nM) were detected, with highest levels being found for 2-arachidonoylglycerol and 17(R)-hydroxydocosahexaenoic acid, respectively. The concentrations of most endocannabinoid-related compounds and oxylipins were dependent on storage condition, and especially storage at 4 °C introduced significant variability. Our findings suggest that human milk samples should be analyzed immediately after, or within one day of collection (if stored at 4 °C). Storage at -80 °C is required for long-term preservation, and storage at -20 °C is acceptable for no more than one week. These findings provide a protocol for investigating the oxylipin and endocannabinoid metabolome in human milk, useful for future milk-related clinical studies.

  • 167. Wutz, Gordana
    et al.
    Várnai, Csilla
    Nagasaka, Kota
    Cisneros, David A.
    Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
    Stocsits, Roman R
    Tang, Wen
    Schoenfelder, Stefan
    Jessberger, Gregor
    Muhar, Matthias
    Hossain, M Julius
    Walther, Nike
    Koch, Birgit
    Kueblbeck, Moritz
    Ellenberg, Jan
    Zuber, Johannes
    Fraser, Peter
    Peters, Jan-Michael
    Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins2017In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 36, no 24, p. 3573-3599Article in journal (Refereed)
    Abstract [en]

    Mammalian genomes are spatially organized into compartments, topologically associating domains (TADs), and loops to facilitate gene regulation and other chromosomal functions. How compartments, TADs, and loops are generated is unknown. It has been proposed that cohesin forms TADs and loops by extruding chromatin loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here, we show that cohesin suppresses compartments but is required for TADs and loops, that CTCF defines their boundaries, and that the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. In the absence of WAPL and PDS5 proteins, cohesin forms extended loops, presumably by passing CTCF sites, accumulates in axial chromosomal positions (vermicelli), and condenses chromosomes. Unexpectedly, PDS5 proteins are also required for boundary function. These results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.

  • 168.
    Yi, Wei
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Inui, Shigeki
    Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Japan.
    Lei, Ting
    Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
    Itami, Satoshi
    Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Japan.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 12011In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 317, no 4, p. 504-512Article in journal (Refereed)
    Abstract [en]

    Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a recently discovered negative regulator of growth factor signaling. The LRIG1 integral membrane protein has been demonstrated to regulate various oncogenic receptor tyrosine kinases, including epidermal growth factor (EGF) receptor (EGFR), by cell-autonomous mechanisms. Here, we investigated whether LRIG1 ectodomains were shed, and if LRIG1 could regulate cell proliferation and EGF signaling in a paracrine manner. Cells constitutively shed LRIG1 ectodomains in vitro, and shedding was modulated by known regulators of metalloproteases, including the ADAM17 specific inhibitor TAPI-2. Furthermore, shedding was enhanced by ectopic expression of Adam17. LRIG1 ectodomains appeared to be shed in vivo, as well, as demonstrated by immunoblotting of mouse and human tissue lysates. Ectopic expression of LRIG1 in lymphocytes suppressed EGF signaling in co-cultured fibroblastoid cells, demonstrating that shed LRIG1 ectodomains can function in a paracrine fashion. Purified LRIG1 ectodomains suppressed EGF signaling without any apparent downregulation of EGFR levels. Taken together, the results show that the LRIG1 ectodomain can be proteolytically shed and can function as a non-cell-autonomous regulator of growth factor signaling. Thus, LRIG1 or its ectodomain could have therapeutic potential in the treatment of growth factor receptor-dependent cancers.

  • 169. Yin, Xiao-Jun
    et al.
    Volk, Sara
    Ljung, Karin
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Mehlmer, Norbert
    Dolezal, Karel
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Laboratory of Growth Regulators, Palacky University and Institute of Experimental Botany, Academy of Sciences of the Czech Republic, CZ-78371 Olomouc, Czech Republic.
    Ditengou, Franck
    Hanano, Shigeru
    Davis, Seth J
    Schmelzer, Elmon
    Sandberg, Göran
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Teige, Markus
    Palme, Klaus
    Pickart, Cecile
    Bachmair, Andreas
    Ubiquitin lysine 63 chain forming ligases regulate apical dominance in Arabidopsis2007In: The Plant Cell, ISSN 1040-4651, E-ISSN 1532-298X, Vol. 19, no 6, p. 1898-1911Article in journal (Refereed)
    Abstract [en]

    Lys-63-linked multiubiquitin chains play important roles in signal transduction in yeast and in mammals, but the functions for this type of chain in plants remain to be defined. The RING domain protein RGLG2 (for RING domain Ligase2) from Arabidopsis thaliana can be N-terminally myristoylated and localizes to the plasma membrane. It can form Lys-63-linked multiubiquitin chains in an in vitro reaction. RGLG2 has overlapping functions with its closest sequelog, RGLG1, and single mutants in either gene are inconspicuous. rglg1 rglg2 double mutant plants exhibit loss of apical dominance and altered phyllotaxy, two traits critically influenced by the plant hormone auxin. Auxin and cytokinin levels are changed, and the plants show a decreased response to exogenously added auxin. Changes in the abundance of PIN family auxin transport proteins and synthetic lethality with a mutation in the auxin transport regulator BIG suggest that the directional flow of auxin is modulated by RGLG activity. Modification of proteins by Lys-63-linked multiubiquitin chains is thus important for hormone-regulated, basic plant architecture.

  • 170. You, Yuan
    et al.
    Sawikowska, Aneta
    Lee, Joanne E.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Benstein, Ruben M.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Neumann, Manuela
    Krajewski, Pawel
    Schmid, Markus
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Max Planck Institute for Developmental Biology, Department of Molecular Biology, Tübingen, Germany; Beijing Advanced Innovation Centre for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, People’s Republic of China.
    Phloem Companion Cell-Specific Transcriptomic and Epigenomic Analyses Identify MRF1, a Regulator of Flowering2019In: The Plant Cell, ISSN 1040-4651, E-ISSN 1532-298X, Vol. 31, no 2, p. 325-345Article in journal (Refereed)
    Abstract [en]

    The phloem plays essential roles in the source-to-sink relationship and in long-distance communication, and thereby coordinates growth and development throughout the plant. Here we employed isolation of nuclei tagged in specific cell types coupled with low-input, high-throughput sequencing approaches to analyze the changes of the chromatin modifications H3K4me3 and H3K27me3 and their correlation with gene expression in the phloem companion cells (PCCs) of Arabidopsis (Arabidopsis thaliana) shoots in response to changes in photoperiod. We observed a positive correlation between changes in expression and H3K4me3 levels of genes that are involved in essential PCC functions, including regulation of metabolism, circadian rhythm, development, and epigenetic modifications. By contrast, changes in H3K27me3 signal appeared to contribute little to gene expression changes. These genomic data illustrate the complex gene-regulatory networks that integrate plant developmental and physiological processes in the PCCs. Emphasizing the importance of cell-specific analyses, we identified a previously uncharacterized MORN-motif repeat protein, MORN-MOTIF REPEAT PROTEIN REGULATING FLOWERING1 (MRF1), that was strongly up-regulated in the PCCs in response to inductive photoperiod. The mrf1 mutation delayed flowering, whereas MRF1 overexpression had the opposite effect, indicating that MRF1 acts as a floral promoter.

  • 171.
    Yu, Fang-Fang
    et al.
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Lin, Xia-Lu
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Wang, Xi
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Liu, Huan
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Yang, Lei
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Goldring, Mary B.
    Hospital for Special Surgery, Weill Cornell Medical College, New York, NY, USA.
    Lammi, Mikko J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Guo, Xiong
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Selenium promotes metabolic conversion of T-2 toxin to HT-2 toxin in cultured human chondrocytes2017In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 44, p. 218-224Article in journal (Refereed)
    Abstract [en]

    To explore the metabolism of T-2 toxin in human chondrocytes (HCs) and determine the impact of selenium supplementation. For determination of cytotoxicity using the MTT assay, optical density values were read with an automatic enzyme-linked immunosorbent assay reader at 510nm. Cell survival was calculated and the cytotoxicity estimated. To identify the metabolites of T-2 toxin, the medium supernatants and C28/I2 cells were analyzed by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) separately. For HPLC-MS/MS, the mobile phase A was water and phase B was 98% methanol. The gradient for the elution was: 0-0.5min, 50% of B; 0.5-2.0min, 100% of B; 2.0-3.5min, 100% of B; 3.6-6min, 50% of B. T-2 toxin increased the toxicity to C28/I2 cells significantly in a dose- and time-dependent manner (viability range 91.5-22.0%). Supplementation with selenium (100ng/mL) could increase the cell viability after the 24h incubation. The concentration of T-2 toxin in the cell medium decreased from 20 to 6.67±1.02ng/mL, and the concentration of HT-2 toxin increased from 0 to 6.88±1.23ng/mL during the 48h incubation, whereas the relative concentration of T-2 toxin in cells increased from 0 to 12.80±1.84ng/g. Supplementary selenium in the HCs cultures reduced the cytotoxicity induced by T-2 toxin significantly, and was associated with rapid conversion of T-2 toxin in the culture medium to HT-2 toxin. T-2 toxin was more toxic to HCs than HT-2 toxin at equivalent concentrations. HT-2 toxin was a detectable metabolite of T-2 toxin in cultured HCs, and selenium enhanced the metabolic conversion of T-2 toxin, reducing its cytotoxicity to HCs.

  • 172.
    Zafra, Olga
    et al.
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Ramírez, Sandra
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Castán, Pablo
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Moreno, Renata
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Cava, Felipe
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Vallés, Cristina
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Caro, Eddy
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    Berenguer, José
    Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus de Cantoblanco, Madrid, Spain.
    A cytochrome c encoded by the nar operon is required for the synthesis of active respiratory nitrate reductase in Thermus thermophilus2002In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 523, no 1-3, p. 99-102Article in journal (Refereed)
    Abstract [en]

    A cytochrome c (NarC) is encoded as the first gene of the operon for nitrate respiration in Thermus thermophilus. NarC is required for anaerobic growth and for the synthesis of active nitrate reductase (NR). The alpha and delta subunits (NarG, NarJ) of the NR were constitutively expressed in narC::kat mutants, but NarG appeared in the soluble fraction instead of associated with the membranes. Our data demonstrate for NarC an essential role in the synthesis of active enzyme and for the attachment to the membrane of the respiratory NR from T. thermophilus.

  • 173.
    Zhao, Guang-Hui
    et al.
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, People's Republic of China.
    Yang, Lei
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, People's Republic of China; School of Nursing, Health Science Center, Xi'an Jiaotong University, Xi'an, People's Republic of China; School of Nursing, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, People's Republic of China.
    Guo, Xiong
    Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, People's Republic of China.
    A preliminary analysis of microRNA profiles in the subchondral bone between Kashin-Beck disease and primary knee osteoarthritis2019In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 38, no 9, p. 2637-2645, article id 31062252Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Kashin-Beck disease (KBD) is a chronic osteochondral disorder primarily associated with cartilage degeneration. The bone texture structure in KBD was also changed but it was not identical to primary knee osteoarthritis (OA). This study investigates the differences in microRNA (miRNA) profiles of subchondral bone collected from patients suffering from KBD in comparison with those with primary knee osteoarthritis (OA).

    METHODS: Subchondral bone tissues were taken from four patients with KBD and four patients with primary knee OA undergoing total knee replacement. The miRNA array profiling was performed using an Affymetrix miRNA 4.0 Array, and then the target gene predictions and function annotations of the predicted targets were performed.

    RESULTS: Our results showed that 124 miRNAs had lower expression levels in the subchondral bone sampled from KBD patients in comparison with OA patients. Gene ontology (GO) and KEGG pathway analyses of the predicted targets demonstrated numerous significantly enriched GO terms and signal pathways essential for bone development and integrity, such as metabolic processes, PI3K-Akt, and MAPK signaling pathways.

    CONCLUSIONS: Our study confirms that a large set of miRNAs are differentially expressed in the subchondral bone of patients with KBD and OA and contributes new insights into potential pathological changes in the subchondral bone of KBD patients.

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