Sample records for psii supercomplex remodeling

  1. Photosystem II supercomplex remodeling serves as an entry mechanism for state transitions in Arabidopsis. (United States)

    Dietzel, Lars; Bräutigam, Katharina; Steiner, Sebastian; Schüffler, Kristin; Lepetit, Bernard; Grimm, Bernhard; Schöttler, Mark Aurel; Pfannschmidt, Thomas


    Within dense plant populations, strong light quality gradients cause unbalanced excitation of the two photosystems resulting in reduced photosynthetic efficiency. Plants redirect such imbalances by structural rearrangements of the photosynthetic apparatus via state transitions and photosystem stoichiometry adjustments. However, less is known about the function of photosystem II (PSII) supercomplexes in this context. Here, we show in Arabidopsis thaliana that PSII supercomplex remodeling precedes and facilitates state transitions. Intriguingly, the remodeling occurs in the short term, paralleling state transitions, but is also present in a state transition-deficient mutant, indicating that PSII supercomplex generation is independently regulated and does not require light-harvesting complex phosphorylation and movement. Instead, PSII supercomplex remodeling involves reversible phosphorylation of PSII core subunits (preferentially of CP43) and requires the luminal PSII subunit Psb27 for general formation and structural stabilization. Arabidopsis knockout mutants lacking Psb27 display highly accelerated state transitions, indicating that release of PSII supercomplexes is required for phosphorylation and subsequent movement of the antenna. Downregulation of PSII supercomplex number by physiological light treatments also results in acceleration of state transitions confirming the genetic analyses. Thus, supercomplex remodeling is a prerequisite and an important kinetic determinant of state transitions.

  2. Proteomic characterization and three-dimensional electron microscopy study of PSII-LHCII supercomplexes from higher plants. (United States)

    Pagliano, Cristina; Nield, Jon; Marsano, Francesco; Pape, Tillmann; Barera, Simone; Saracco, Guido; Barber, James


    In higher plants a variable number of peripheral LHCII trimers can strongly (S), moderately (M) or loosely (L) associate with the dimeric PSII core (C2) complex via monomeric Lhcb proteins to form PSII-LHCII supercomplexes with different structural organizations. By solubilizing isolated stacked pea thylakoid membranes either with the α or β isomeric forms of the detergent n-dodecyl-D-maltoside, followed by sucrose density ultracentrifugation, we previously showed that PSII-LHCII supercomplexes of types C2S2M2 and C2S2, respectively, can be isolated [S. Barera et al., Phil. Trans. R Soc. B 67 (2012) 3389-3399]. Here we analysed their protein composition by applying extensive bottom-up and top-down mass spectrometry on the two forms of the isolated supercomplexes. In this way, we revealed the presence of the antenna proteins Lhcb3 and Lhcb6 and of the extrinsic polypeptides PsbP, PsbQ and PsbR exclusively in the C2S2M2 supercomplex. Other proteins of the PSII core complex, common to the C2S2M2 and C2S2 supercomplexes, including the low molecular mass subunits, were also detected and characterized. To complement the proteomic study with structural information, we performed negative stain transmission electron microscopy and single particle analysis on the PSII-LHCII supercomplexes isolated from pea thylakoid membranes solubilized with n-dodecyl-α-D-maltoside. We observed the C2S2M2 supercomplex in its intact form as the largest PSII complex in our preparations. Its dataset was further analysed in silico, together with that of the second largest identified sub-population, corresponding to its C2S2 subcomplex. In this way, we calculated 3D electron density maps for the C2S2M2 and C2S2 supercomplexes, approaching respectively 30 and 28Å resolution, extended by molecular modelling towards the atomic level. This article is part of a special issue entitled: photosynthesis research for sustainability: keys to produce clean energy. Copyright © 2013. Published by

  3. Arabidopsis plants lacking PsbQ and PsbR subunits of the oxygen-evolving complex show altered PSII super-complex organization and short-term adaptive mechanisms. (United States)

    Allahverdiyeva, Yagut; Suorsa, Marjaana; Rossi, Fabio; Pavesi, Andrea; Kater, Martin M; Antonacci, Alessia; Tadini, Luca; Pribil, Mathias; Schneider, Anja; Wanner, Gerhard; Leister, Dario; Aro, Eva-Mari; Barbato, Roberto; Pesaresi, Paolo


    The oxygen-evolving complex of eukaryotic photosystem II (PSII) consists of four extrinsic subunits, PsbO (33 kDa), PsbP (23 kDa), PsbQ (17 kDa) and PsbR (10 kDa), encoded by seven nuclear genes, PsbO1 (At5g66570), PsbO2 (At3g50820), PsbP1 (At1g06680), PsbP2 (At2g30790), PsbQ1 (At4g21280), PsbQ2 (At4g05180) and PsbR (At1g79040). Using Arabidopsis insertion mutant lines, we show that PsbP1, but not PsbP2, is essential for photoautotrophic growth, whereas plants lacking both forms of PsbQ and/or PsbR show normal growth rates. Complete elimination of PsbQ has a minor effect on PSII function, but plants lacking PsbR or both PsbR and PsbQ are characterized by more pronounced defects in PSII activity. Gene expression and immunoblot analyses indicate that accumulation of each of these proteins is highly dependent on the presence of the others, and is controlled at the post-transcriptional level, whereas PsbO stability appears to be less sensitive to depletion of other subunits of the oxygen-evolving complex. In addition, comparison of levels of the PSII super-complex in wild-type and mutant leaves reveals the importance of the individual subunits of the oxygen-evolving complex for the supramolecular organization of PSII and their influence on the rate of state transitions. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  4. Subunit and chlorophyll organization of the plant photosystem II supercomplex

    NARCIS (Netherlands)

    van Bezouwen, Laura S; Caffarri, Stefano; Kale, Ravindra S; Kouřil, Roman; Thunnissen, Andy-Mark W H; Oostergetel, Gert T; Boekema, Egbert J


    Photosystem II (PSII) is a light-driven protein, involved in the primary reactions of photosynthesis. In plant photosynthetic membranes PSII forms large multisubunit supercomplexes, containing a dimeric core and up to four light-harvesting complexes (LHCs), which act as antenna proteins. Here we

  5. Supercomplexes of photosystem I and antenna proteins in cyanobacteria and green plants

    NARCIS (Netherlands)

    Kouril, R.; Zygadlo, A.; Jensen, P. E.; Yeremenko, N.; Matthijs, H.C.P.; D'Haene, S.; Dekker, J.P.; Boekema, E.J.; Matthijs, H.C.P.


    Photosystem I (PSI) and Photosystem II (PSII) can form supercomplexes with various types of antenna proteins. One such protein is Light-harvesting complex II (LHCII). In plants it is bound in its trimeric form to dimeric PSII. In spinach and Arabidopsis thaliana most dimers bind 2-4 LHCII trimers.

  6. Subunit and chlorophyll organization of the plant photosystem II supercomplex. (United States)

    van Bezouwen, Laura S; Caffarri, Stefano; Kale, Ravindra S; Kouřil, Roman; Thunnissen, Andy-Mark W H; Oostergetel, Gert T; Boekema, Egbert J


    Photosystem II (PSII) is a light-driven protein, involved in the primary reactions of photosynthesis. In plant photosynthetic membranes PSII forms large multisubunit supercomplexes, containing a dimeric core and up to four light-harvesting complexes (LHCs), which act as antenna proteins. Here we solved a three-dimensional (3D) structure of the C2S2M2 supercomplex from Arabidopsis thaliana using cryo-transmission electron microscopy (cryo-EM) and single-particle analysis at an overall resolution of 5.3 Å. Using a combination of homology modelling and restrained refinement against the cryo-EM map, it was possible to model atomic structures for all antenna complexes and almost all core subunits. We located all 35 chlorophylls of the core region based on the cyanobacterial PSII structure, whose positioning is highly conserved, as well as all the chlorophylls of the LHCII S and M trimers. A total of 13 and 9 chlorophylls were identified in CP26 and CP24, respectively. Energy flow from LHC complexes to the PSII reaction centre is proposed to follow preferential pathways: CP26 and CP29 directly transfer to the core using several routes for efficient transfer; the S trimer is directly connected to CP43 and the M trimer can efficiently transfer energy to the core through CP29 and the S trimer.

  7. Supercomplexity and the university

    DEFF Research Database (Denmark)

    Bengtsen, Søren Smedegaard


    Ronald Barnett’s modern classic Realizing the University in an Age of Supercomplexity (published December 1999), has had a crucial impact internationally on the field of Higher Education research and develop- ment since the book was published now nearly 20 years ago. Bridging an academic oeuvre...... across almost 30 years with close to 30 published volumes, Realizing the University in an Age of Supercomplexity plays an important role in the development and transformation of Barnett’s social theory of Higher Education into a social philosophy of Higher Education. In the book Barnett performs...... an important move from a focus on knowledge and epistemology to a focus on being and ontol- ogy in relation to Higher Education practices. Barnett shifts his fundamental perspective and view on the relation between universities and the wider society from one of caution and worry to a perspective of hope...

  8. Functional architecture of higher plant photosystem II supercomplexes. (United States)

    Caffarri, Stefano; Kouril, Roman; Kereïche, Sami; Boekema, Egbert J; Croce, Roberta


    Photosystem II (PSII) is a large multiprotein complex, which catalyses water splitting and plastoquinone reduction necessary to transform sunlight into chemical energy. Detailed functional and structural studies of the complex from higher plants have been hampered by the impossibility to purify it to homogeneity. In this work, homogeneous preparations ranging from a newly identified particle composed by a monomeric core and antenna proteins to the largest C(2)S(2)M(2) supercomplex were isolated. Characterization by biochemical methods and single particle electron microscopy allowed to relate for the first time the supramolecular organization to the protein content. A projection map of C(2)S(2)M(2) at 12 A resolution was obtained, which allowed determining the location and the orientation of the antenna proteins. Comparison of the supercomplexes obtained from WT and Lhcb-deficient plants reveals the importance of the individual subunits for the supramolecular organization. The functional implications of these findings are discussed and allow redefining previous suggestions on PSII energy transfer, assembly, photoinhibition, state transition and non-photochemical quenching.

  9. Supercomplexity in Higher Education Kinesiology (United States)

    Block, Betty A.; Estes, Steve


    This article employs Barnett's (2004) specifications of the aspects that describe the times of "supercomplexity." This term characterizes the challenges universities are facing regarding the expanding and competing forces that are affecting higher education, particularly in the West. Outside forces related to globalization, digital technologies,…

  10. Evidence of the supercomplex organization of photosystem II and light-harvesting complexes in Nannochloropsis granulata. (United States)

    Umetani, Ikumi; Kunugi, Motoshi; Yokono, Makio; Takabayashi, Atsushi; Tanaka, Ayumi


    Diverse light-harvesting complexes (LHCs) have been found in photosynthetic microalgae that originated from secondary endosymbiosis involving primary red algae. However, the associations between LHCs and photosystem I (PSI) and photosystem II (PSII) in these microalgae are not fully understood. Eustigmatophyta is a red algal lineage that appears to have a unique organization in its photosynthetic machinery, consisting of only chlorophyll a and carotenoids that are atypical compared with other closely related groups. In this study, the supramolecular organization of pigment-protein complexes in the eustigmatophyte alga, Nannochloropsis granulata was investigated using Clear Native (CN) PAGE coupled with two-dimensional (2D) SDS-PAGE. Our results showed two slowly migrating green bands that corresponded to PSII supercomplexes, which consisted of reaction centers and LHCs. These green bands were also characterized as PSII complexes by their low temperature fluorescence emission spectra. The protein subunits of the PSII-LHC resolved by 2D CN/SDS-PAGE were analyzed by mass spectrometry, and four different LHC proteins were identified. Phylogenetic analysis of the identified LHC protein sequences revealed that they belonged to four different Lhc groups; (1) stress-related Lhcx proteins, (2) fucoxanthin chlorophyll a/c-binding Lhcf proteins, (3) red-shifted Chromera light-harvesting proteins (Red-CLH), and (4) Lhcr proteins, which are commonly found in organisms possessing red algal plastids. This is the first report showing evidence of a pigment-protein supercomplex consisting of PSII and LHCs, and to identify PSII-associated LHC proteins in Nannochloropsis.

  11. Isolation of novel PSII-LHCII megacomplexes from pea plants characterized by a combination of proteomics and electron microscopy. (United States)

    Albanese, Pascal; Nield, Jon; Tabares, Jose Alejandro Muñoz; Chiodoni, Angelica; Manfredi, Marcello; Gosetti, Fabio; Marengo, Emilio; Saracco, Guido; Barber, James; Pagliano, Cristina


    In higher plants, photosystem II (PSII) is a multi-subunit pigment-protein complex embedded in the thylakoid membranes of chloroplasts, where it is present mostly in dimeric form within the grana. Its light-harvesting antenna system, LHCII, is composed of trimeric and monomeric complexes, which can associate in variable number with the dimeric PSII core complex in order to form different types of PSII-LHCII supercomplexes. Moreover, PSII-LHCII supercomplexes can laterally associate within the thylakoid membrane plane, thus forming higher molecular mass complexes, termed PSII-LHCII megacomplexes (Boekema et al. 1999a, in Biochemistry 38:2233-2239; Boekema et al. 1999b, in Eur J Biochem 266:444-452). In this study, pure PSII-LHCII megacomplexes were directly isolated from stacked pea thylakoid membranes by a rapid single-step solubilization, using the detergent n-dodecyl-α-D-maltoside, followed by sucrose gradient ultracentrifugation. The megacomplexes were subjected to biochemical and structural analyses. Transmission electron microscopy on negatively stained samples, followed by single-particle analyses, revealed a novel form of PSII-LHCII megacomplexes, as compared to previous studies (Boekema et al.1999a, in Biochemistry 38:2233-2239; Boekema et al. 1999b, in Eur J Biochem 266:444-452), consisting of two PSII-LHCII supercomplexes sitting side-by-side in the membrane plane, sandwiched together with a second copy. This second copy of the megacomplex is most likely derived from the opposite membrane of a granal stack. Two predominant forms of intact sandwiched megacomplexes were observed and termed, according to (Dekker and Boekema 2005 Biochim Biophys Acta 1706:12-39), as (C2S2)4 and (C2S2 + C2S2M2)2 megacomplexes. By applying a gel-based proteomic approach, the protein composition of the isolated megacomplexes was fully characterized. In summary, the new structural forms of isolated megacomplexes and the related modeling performed provide novel insights into

  12. Kinetics and heterogeneity of energy transfer from light harvesting complex II to photosystem I in the supercomplex isolated from Arabidopsis. (United States)

    Santabarbara, Stefano; Tibiletti, Tania; Remelli, William; Caffarri, Stefano


    State transitions are a phenomenon that maintains the excitation balance between photosystem II (PSII) and photosystem I (PSI-LHCI) by controlling their relative absorption cross-sections. Under light conditions exciting PSII preferentially, a trimeric LHCII antenna moves from PSII to PSI-LHCI to form the PSI-LHCI-LHCII supercomplex. In this work, the excited state dynamics in the PSI-LHCI and PSI-LHCI-LHCII supercomplexes isolated from Arabidopsis have been investigated by picosecond time-resolved fluorescence spectroscopy. The excited state decays were analysed using two approaches based on either (i) a sum of discrete exponentials or (ii) a continuous distribution of lifetimes. The results indicate that the energy transfer from LHCII to the bulk of the PSI antenna occurs with an average macroscopic transfer rate in the 35-65 ns-1 interval. Yet, the most satisfactory description of the data is obtained when considering a heterogeneous population containing two PSI-LHCI-LHCII supercomplexes characterised by a transfer time of ∼15 and ∼60 ns-1, likely due to the differences in the strength and orientation of LHCII harboured to PSI. Both these values are of the same order of magnitude of those estimated for the average energy transfer rates from the low energy spectral forms of LHCI to the bulk of the PSI antenna (15-40 ns-1), but they are slower than the transfer from the bulk antenna of PSI to the reaction centre (>150 ns-1), implying a relatively small kinetics bottleneck for the energy transfer from LHCII. Nevertheless, the kinetic limitation imposed by excited state diffusion has a negligible impact on the photochemical quantum efficiency of the supercomplex, which remains about 98% in the case of PSI-LHCI.

  13. Attachment of phycobilisomes in an antenna-photosystem I supercomplex of cyanobacteria. (United States)

    Watanabe, Mai; Semchonok, Dmitry A; Webber-Birungi, Mariam T; Ehira, Shigeki; Kondo, Kumiko; Narikawa, Rei; Ohmori, Masayuki; Boekema, Egbert J; Ikeuchi, Masahiko


    Oxygenic photosynthesis is driven by photosystems I and II (PSI and PSII, respectively). Both have specific antenna complexes and the phycobilisome (PBS) is the major antenna protein complex in cyanobacteria, typically consisting of a core from which several rod-like subcomplexes protrude. PBS preferentially transfers light energy to PSII, whereas a PSI-specific antenna has not been identified. The cyanobacterium Anabaena sp. PCC 7120 has rod-core linker genes (cpcG1-cpcG2-cpcG3-cpcG4). Their products, except CpcG3, have been detected in the conventional PBS. Here we report the isolation of a supercomplex that comprises a PSI tetramer and a second, unique type of a PBS, specific to PSI. This rod-shaped PBS includes phycocyanin (PC) and CpcG3 (hereafter renamed "CpcL"), but no allophycocyanin or CpcGs. Fluorescence excitation showed efficient energy transfer from PBS to PSI. The supercomplex was analyzed by electron microscopy and single-particle averaging. In the supercomplex, one to three rod-shaped CpcL-PBSs associate to a tetrameric PSI complex. They are mostly composed of two hexameric PC units and bind at the periphery of PSI, at the interfaces of two monomers. Structural modeling indicates, based on 2D projection maps, how the PsaI, PsaL, and PsaM subunits link PSI monomers into dimers and into a rhombically shaped tetramer or "pseudotetramer." The 3D model further shows where PBSs associate with the large subunits PsaA and PsaB of PSI. It is proposed that the alternative form of CpcL-PBS is functional in harvesting energy in a wide number of cyanobacteria, partially to facilitate the involvement of PSI in nitrogen fixation.

  14. Lead induced changes in phosphorylation of PSII proteins in low light grown pea plants. (United States)

    Wioleta, Wasilewska; Anna, Drożak; Ilona, Bacławska; Kamila, Kąkol; Elżbieta, Romanowska


    Light-intensity and redox-state induced thylakoid proteins phosphorylation involved in structural changes and in regulation of protein turnover. The presence of heavy metal ions triggers a wide range of cellular responses including changes in plant growth and photosynthesis. Plants have evolved a number of mechanisms to protect photosynthetic apparatus. We have characterized the effect of lead on PSII protein phosphorylation in pea (Pisum sativum L.) plants grown in low light conditions. Pb ions affected only slightly photochemical efficiency of PSII and had no effect on organization of thylakoid complexes. Lead activated strongly phosphorylation of PSII core D1 protein and dephosphorylation of this protein did not proceed in far red light. D1 protein was also not degraded in this conditions. However, phosphorylation of LHCII proteins was not affected by lead. These results indicate that Pb(2+) stimulate the phosphorylation of PSII core proteins and by disturbing the disassembly of supercomplexes play a role in PSII repair mechanism. LHCII phosphorylation could control the distribution of energy between the photosystems in low light conditions. This demonstrates that plants may respond to heavy metals by induction different pathways responsible for protein protection under stress conditions.

  15. Megacomplex organization of the oxidative phosphorylation system by structural analysis of respiratory supercomplexes from potato

    NARCIS (Netherlands)

    Bultema, Jelle B.; Braun, Hans-Peter; Boekema, Egbert J.; Kouřil, Roman

    The individual protein complexes of the oxidative phosphorylation system (OXPHOS complexes 1 to V) specifically interact and form defined supramolecular structures, the so-called "respiratory supercomplexes". Some supercomplexes appear to associate into larger structures, or megacomplexes, such as a

  16. Towards structural and functional characterization of photosynthetic and mitochondrial supercomplexes

    NARCIS (Netherlands)

    Dudkina, Natalya V.; Folea, I Mihaela; Boekema, Egbert J


    Bioenergetic reactions in chloroplasts and mitochondria are catalyzed by large multi-subunit membrane proteins. About two decades ago it became clear that several of these large membrane proteins further associate into supercomplexes and since then a number of new ones have been described. In this

  17. An Australian Perspective on Teacher Professional Development in Supercomplex Times


    Lorraine M. Ling; Noella M. Mackenzie


    Professional Development is one of many terms given to the in-service education and training of teachers. In this paper, the authors address the kinds of professional development currently offered in Australia and compare it with the kinds of professional development teachers may require to deal with an era of supercomplexity, where there is uncertainty, insecurity and an unknown and unknowable future. Professional development is seen as involving multiple stakeholders and the influence of go...

  18. Functional architecture of higher plant photosystem II supercomplexes

    NARCIS (Netherlands)

    Caffarri, Stefano; Kouril, Roman; Kereiche, Sami; Boekema, Egbert J.; Croce, Roberta; Kereïche, Sami


    Photosystem II ( PSII) is a large multiprotein complex, which catalyses water splitting and plastoquinone reduction necessary to transform sunlight into chemical energy. Detailed functional and structural studies of the complex from higher plants have been hampered by the impossibility to purify it

  19. Stable megadalton TOC-TIC supercomplexes as major mediators of protein import into chloroplasts. (United States)

    Chen, Lih-Jen; Li, Hsou-Min


    Preproteins are believed to be imported into chloroplasts through membrane contact sites where the translocon complexes of the outer (TOC) and inner (TIC) envelope membranes are assembled together. However, a single TOC-TIC supercomplex containing preproteins undergoing active import has not yet been directly observed. We optimized the blue native polyacrylamide gel electrophoresis (PAGE) (BN-PAGE) system to detect and resolve megadalton (MD)-sized complexes. Using this optimized system, the outer-membrane channel Toc75 from pea chloroplasts was found in at least two complexes: the 880-kD TOC complex and a previously undetected 1-MD complex. Two-dimensional BN-PAGE immunoblots further showed that Toc75, Toc159, Toc34, Tic20, Tic56 and Tic110 were all located in the 880-kD to 1.3-MD region. During active preprotein import, preproteins were transported mostly through the 1-MD complex and a smaller amount of preproteins was also detected in a complex of 1.25 MD. Antibody-shift assays showed that the 1-MD complex is a TOC-TIC supercomplex containing at least Toc75, Toc159, Toc34 and Tic110. Results from crosslinking and import with Arabidopsis chloroplasts suggest that the 1.25-MD complex is also a supercomplex. Our data provide direct evidence supporting that chloroplast preproteins are imported through TOC-TIC supercomplexes, and also provide the first size estimation of these supercomplexes. Furthermore, unlike in mitochondria where translocon supercomplexes are only transiently assembled during preprotein import, in chloroplasts at least some of the supercomplexes are preassembled stable structures. © 2017 The Authors The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

  20. State transitions--the molecular remodeling of photosynthetic supercomplexes that controls energy flow in the chloroplast. (United States)

    Minagawa, Jun


    In oxygen-evolving photosynthesis, the two photosystems-photosystem I and photosystem II-function in parallel, and their excitation levels must be balanced to maintain an optimal photosynthetic rate under natural light conditions. State transitions in photosynthetic organisms balance the absorbed light energy between the two photosystems in a short time by relocating light-harvesting complex II proteins. For over a decade, the understanding of the physiological consequences, the molecular mechanism, and its regulation has increased considerably. After providing an overview of the general understanding of state transitions, this review focuses on the recent advances of the molecular aspects of state transitions with a particular emphasis on the studies using the green alga Chlamydomonas reinhardtii. This article is part of a Special Issue entitled: Regulation of Electron Transport in Chloroplasts. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Are dental students ready for supercomplex dental practice? (United States)

    Leadbeatter, D; Peck, C


    Contemporary dental practice requires practitioners who are able to draw upon varying interconnected knowledge and skills, in order to make judgments and take action when faced with multiple, often contradictory, ways of interpreting a situation. However, the curricula that prepare students for dental practice are traditionally based on the theoretical knowledge and technical skills to be gained by students. This is despite evidence in the dental literature of a collective desire for graduates to have more range and depth in their repertoire. Examination of contemporary dental practice through the lens of supercomplexity (Higher Education, 40, 409 and 2000) provides contextual understanding and a platform to explore the types of learning and curriculum approaches that can best prepare students for professional practice. From the insights offered by examples from other professional fields, we, as dental educators, can begin to conceptualise learning dentistry as much more than competency frameworks or descriptions of what students need to know and be able to do. Rather, to equip graduates for contemporary dental practice, the dental curriculum needs to become a vehicle for students to develop personally and professionally as well as teaching the theoretical and technical aspects of dentistry. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Association of Psb28 and Psb27 Proteins with PSII-PSI Supercomplexes upon Exposure of Synechocystis sp PCC 6803 to High Light

    Czech Academy of Sciences Publication Activity Database

    Bečková, Martina; Gardian, Zdenko; Yu, J.F.; Koník, Peter; Nixon, P. J.; Komenda, Josef


    Roč. 10, č. 1 (2017), s. 62-72 ISSN 1674-2052 R&D Projects: GA ČR GBP501/12/G055; GA MŠk(CZ) LO1416; GA MŠk(CZ) ED2.1.00/19.0392 Institutional support: RVO:61388971 ; RVO:60077344 Keywords : Psb28 proteins * photosystem I and II * Synechocystis Subject RIV: EE - Microbiology, Virology; CE - Biochemistry (BC-A) Impact factor: 8.827, year: 2016

  3. Rice Photosynthetic Productivity and PSII Photochemistry under Nonflooded Irrigation

    Directory of Open Access Journals (Sweden)

    Haibing He


    Full Text Available Nonflooded irrigation is an important water-saving rice cultivation technology, but little is known on its photosynthetic mechanism. The aims of this work were to investigate photosynthetic characteristics of rice during grain filling stage under three nonflooded irrigation treatments: furrow irrigation with plastic mulching (FIM, furrow irrigation with nonmulching (FIN, and drip irrigation with plastic mulching (DI. Compared with the conventional flooding (CF treatment, those grown in the nonflooded irrigation treatments showed lower net photosynthetic rate (PN, lower maximum quantum yield (Fv/Fm, and lower effective quantum yield of PSII photochemistry (ΦPSII. And the poor photosynthetic characteristics in the nonflooded irrigation treatments were mainly attributed to the low total nitrogen content (TNC. Under non-flooded irrigation, the PN, Fv/Fm, and ΦPSII significantly decreased with a reduction in the soil water potential, but these parameters were rapidly recovered in the DI and FIM treatments when supplementary irrigation was applied. Moreover, The DI treatment always had higher photosynthetic productivity than the FIM and FIN treatments. Grain yield, matter translocation, and dry matter post-anthesis (DMPA were the highest in the CF treatment, followed by the DI, FIM, and FIN treatments in turn. In conclusion, increasing nitrogen content in leaf of rice plants could be a key factor to improve photosynthetic capacity in nonflooded irrigation.

  4. Supercomplexity and the University: Ronald Barnett and the Social Philosophy of Higher Education (United States)

    Bengtsen, Søren S. E.


    Ronald Barnett's modern classic "Realizing the University in an Age of Supercomplexity" (published December 1999), has had a crucial impact internationally on the field of Higher Education research and development since the book was published now nearly 20 years ago. Bridging an academic oeuvre across almost 30 years with close to 30…

  5. Structure and functional role of supercomplexes of IsiA and Photosystem I in cyanobacterial photosynthesis

    NARCIS (Netherlands)

    Kouril, R.; Arteni, A.A.; Lax, J.; Yeremenko, N.; D'Haene, S.; Rogner, M.; Matthijs, H.C.P.; Dekker, J.P.; Boekema, E.J.


    Cyanobacteria express large quantities of the iron stress-inducible protein IsiA under iron deficiency. IsiA can assemble into numerous types of single or double rings surrounding Photosystem I. These supercomplexes are functional in light-harvesting, empty IsiA rings are effective energy

  6. Arrangement of photosystem II supercomplexes in crystalline macrodomains within the thylakoid membrane of green plant chloroplasts

    NARCIS (Netherlands)

    Boekema, EJ; van Breemen, JFL; van Roon, H; Dekker, JP; Dekker, Jan P.


    The chloroplast thylakoid membrane of green plants is organized in stacked grana membranes and unstacked stroma membranes. We investigated the structural organization of Photosystem II (PSII) in paired grana membrane fragments by transmission electron microscopy. The membrane fragments were obtained

  7. [On specific properties of the mitochondrial oxidative phosphorylation system operating as a supercomplex]. (United States)

    Nesterov, S V; Skorobogatova, Iu A; Iaguzhinskiĭ, L S


    This paper represents the study of endogenous and exogenous fatty acids affecting the mitochondrial phosphorylation system effectiveness depending on temperature. The experiment was set up under conditions in which the oxidative phosphorylation system operates as a supercomplex. Rat liver mitochondria were isolated without purposive fatty acids removal from membranes, then studied in hypotonic medium (120 mOsm). We managed to detect a very narrow interval 19 ± 1°C where the fatty acid uncoupling effect is weak up to disappearing. At the same small temperature range, a structural rearrangement that takes place in the enzyme system is accompanied with denser packing of membrane protein complexes. Thus, at the temperatures close to 19°C the supercomplex works in the specific regime protected (or partially protected) from the uncoupling effect of fatty acids. Here we also discuss a physiological significance of the increased ATP-synthesis effectiveness at lower temperatures and the most probable character of structural rearrangement taking place at 19°C in the enzymes in the mitochondrial membrane.

  8. Supercomplexes of plant photosystem I with cytochrome b6f, light-harvesting complex II and NDH

    NARCIS (Netherlands)

    Yadav, K N Sathish; Semchonok, Dmitry A; Nosek, Lukáš; Kouřil, Roman; Fucile, Geoffrey; Boekema, Egbert J; Eichacker, Lutz A

    Photosystem I (PSI) is a pigment-protein complex required for the light-dependent reactions of photosynthesis and participates in light-harvesting and redox-driven chloroplast metabolism. Assembly of PSI into supercomplexes with light harvesting complex (LHC) II, cytochrome b6f (Cytb6f) or NAD(P)H

  9. Attachment of phycobilisomes in an antenna–photosystem I supercomplex of cyanobacteria

    NARCIS (Netherlands)

    Watanabe, Mai; Semchonok, Dmitry A.; Webber-Birungi, Mariam T.; Ehira, Shigeki; Kondo, Kumiko; Narikawa, Rei; Ohmori, Masayuki; Boekema, Egbert J.; Ikeuchi, Masahiko; Haselkorn, Robert


    Oxygenic photosynthesis is driven by photosystems I and II (PSI and PSII, respectively). Both have specific antenna complexes and the phycobilisome (PBS) is the major antenna protein complex in cyanobacteria, typically consisting of a core from which several rod-like subcomplexes protrude. PBS

  10. Supercomplexes of plant photosystem I with cytochrome b6f, light-harvesting complex II and NDH. (United States)

    Yadav, K N Sathish; Semchonok, Dmitry A; Nosek, Lukáš; Kouřil, Roman; Fucile, Geoffrey; Boekema, Egbert J; Eichacker, Lutz A


    Photosystem I (PSI) is a pigment-protein complex required for the light-dependent reactions of photosynthesis and participates in light-harvesting and redox-driven chloroplast metabolism. Assembly of PSI into supercomplexes with light harvesting complex (LHC) II, cytochrome b6f (Cytb6f) or NAD(P)H dehydrogenase complex (NDH) has been proposed as a means for regulating photosynthesis. However, structural details about the binding positions in plant PSI are lacking. We analyzed large data sets of electron microscopy single particle projections of supercomplexes obtained from the stroma membrane of Arabidopsis thaliana. By single particle analysis, we established the binding position of Cytb6f at the antenna side of PSI. The rectangular-shaped Cytb6f dimer binds at the side where Lhca1 is located. The complex binds with its short side rather than its long side to PSI, which may explain why these supercomplexes are difficult to purify and easily disrupted. Refined analysis of the interaction between PSI and the NDH complex indicates that in total up to 6 copies of PSI can arrange with one NDH complex. Most PSI-NDH supercomplexes appeared to have 1-3 PSI copies associated. Finally, the PSI-LHCII supercomplex was found to bind an additional LHCII trimer at two positions on the LHCI side in Arabidopsis. The organization of PSI, either in a complex with NDH or with Cytb6f, may improve regulation of electron transport by the control of binding partners and distances in small domains. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Chemical Crosslinking Mass Spectrometry Analysis of Protein Conformations and Supercomplexes in Heart Tissue. (United States)

    Chavez, Juan D; Lee, Chi Fung; Caudal, Arianne; Keller, Andrew; Tian, Rong; Bruce, James E


    While modern structural biology technologies have greatly expanded the size and type of protein complexes that can now be studied, the ability to derive large-scale structural information on proteins and complexes as they exist within tissues is practically nonexistent. Here, we demonstrate the application of crosslinking mass spectrometry to identify protein structural features and interactions in tissue samples, providing systems structural biology insight into protein complexes as they exist in the mouse heart. This includes insights into multiple conformational states of sarcomere proteins, as well as interactions among OXPHOS complexes indicative of supercomplex assembly. The extension of crosslinking mass spectrometry analysis into the realm of tissues opens the door to increasing our understanding of protein structures and interactions within the context of the greater biological system. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Chloroplast movement provides photoprotection to plants by redistributing PSII damage within leaves. (United States)

    Davis, Phillip A; Hangarter, Roger P


    Plants use light to fix carbon through the process of photosynthesis but light also causes photoinhibition, by damaging photosystem II (PSII). Plants can usually adjust their rate of PSII repair to equal the rate of damage, but under stress conditions or supersaturating light-intensities damage may exceed the rate of repair. Light-induced chloroplast movements are one of the many mechanisms plants have evolved to minimize photoinhibition. We found that chloroplast movements achieve a measure of photoprotection to PSII by altering the distribution of photoinhibition through depth in leaves. When chloroplasts are in the low-light accumulation arrangement a greater proportion of PSII damage occurs near the illuminated surface than for leaves where the chloroplasts are in the high-light avoidance arrangement. According to our findings chloroplast movements can increase the overall efficiency of leaf photosynthesis in at least two ways. The movements alter light profiles within leaves to maximize photosynthetic output and at the same time redistribute PSII damage throughout the leaf to reduce the amount of inhibition received by individual chloroplasts and prevent a decrease in photosynthetic potential.

  13. Isolation and Characterization of a Hybrid Respiratory Supercomplex Consisting of Mycobacterium tuberculosis Cytochrome bcc and Mycobacterium smegmatis Cytochrome aa3. (United States)

    Kim, Mi-Sun; Jang, Jichan; Ab Rahman, Nurlilah Binte; Pethe, Kevin; Berry, Edward A; Huang, Li-Shar


    Recently, energy production pathways have been shown to be viable antitubercular drug targets to combat multidrug-resistant tuberculosis and eliminate pathogen in the dormant state. One family of drugs currently under development, the imidazo[1,2-a]pyridine derivatives, is believed to target the pathogen's homolog of the mitochondrial bc1 complex. This complex, denoted cytochrome bcc, is highly divergent from mitochondrial Complex III both in subunit structure and inhibitor sensitivity, making it a good target for drug development. There is no soluble cytochrome c in mycobacteria to transport electrons from the bcc complex to cytochrome oxidase. Instead, the bcc complex exists in a "supercomplex" with a cytochrome aa3-type cytochrome oxidase, presumably allowing direct electron transfer. We describe here purification and initial characterization of the mycobacterial cytochrome bcc-aa3 supercomplex using a strain of M. smegmatis that has been engineered to express the M. tuberculosis cytochrome bcc. The resulting hybrid supercomplex is stable during extraction and purification in the presence of dodecyl maltoside detergent. It is hoped that this purification procedure will potentiate functional studies of the complex as well as crystallographic studies of drug binding and provide structural insight into a third class of the bc complex superfamily. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Light dependence of quantum yields for PSII charge separation and oxygen evolution in eucaryotic algae

    NARCIS (Netherlands)

    Flameling, I.A.; Kromkamp, J.C.


    Quantum yields of photosystem II (PSII) charge separation (Phi(P)) and oxygen production (Phi(O2)) were determined by simultaneous measurements of oxygen production and variable fluorescence in four different aquatic microalgae representing three different taxonomic groups: the freshwater alga

  15. Oxyradicals and PSII activity in maize leaves in the absence of UV ...

    Indian Academy of Sciences (India)

    ... oxyradicals invoked higher activity of antioxidant enzymes like superoxide dismutase and peroxidase under ambient UV, they also imposed limitation on the photosynthetic efficiency of PSII. Exclusion of UV components (UV-B 280–315 nm; UV-A 315–400 nm) translated to enhanced photosynthesis, growth and biomass.

  16. In vivo assessment of effect of phytotoxin tenuazonic acid on PSII reaction centers. (United States)

    Chen, Shiguo; Strasser, Reto Jörg; Qiang, Sheng


    Tenuazonic acid (TeA), a phytotoxin produced by the fungus Alternaria alternata isolated from diseased croftonweed (Ageratina adenophora), exhibits a strong inhibition in photosystem II (PSII) activity. In vivo chlorophyll fluorescence transients of the host plant croftonweed, show that the dominant effect of TeA is not on the primary photochemical reaction but on the biochemical reaction after QA. The most important action site of TeA is the QB site on the PSII electron-acceptor side, blocking electron transport beyond QA(-) by occupying the QB site in the D1 protein. However, TeA does not affect the antenna pigments, the energy transfer from antenna pigment molecules to reaction centers (RCs), and the oxygen-evolving complex (OEC) at the donor side of PSII. TeA severely inactivated PSII RCs. The fraction of non-QA reducing centers and non-QB reducing centers show a time- and concentration-dependent linear increase. Conversely, the amount of active QA or QB reducing centers declined sharply in a linear way. The fraction of non-QB reducing centers calculated from data of fluorescence transients is close to the number of PSII RCs with their QB site filled by TeA. An increase of the step-J level (VJ) in the OJIP fluorescence transients attributed to QA(-) accumulation due to TeA bound to the QB site is a typical characteristic response of the plants leaf with respect to TeA penetration. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Overexpressed Superoxide Dismutase and Catalase Act Synergistically to Protect the Repair of PSII during Photoinhibition in Synechococcus elongatus PCC 7942. (United States)

    Sae-Tang, Penporn; Hihara, Yukako; Yumoto, Isao; Orikasa, Yoshitake; Okuyama, Hidetoshi; Nishiyama, Yoshitaka


    The repair of PSII under strong light is particularly sensitive to reactive oxygen species (ROS), such as the superoxide radical and hydrogen peroxide, and these ROS are efficiently scavenged by superoxide dismutase (SOD) and catalase. In the present study, we generated transformants of the cyanobacterium Synechococcus elongatus PCC 7942 that overexpressed an iron superoxide dismutase (Fe-SOD) from Synechocystis sp. PCC 6803; a highly active catalase (VktA) from Vibrio rumoiensis; and both enzymes together. Then we examined the sensitivity of PSII to photoinhibition in the three strains. In cells that overexpressed either Fe-SOD or VktA, PSII was more tolerant to strong light than it was in wild-type cells. Moreover, in cells that overexpressed both Fe-SOD and VktA, PSII was even more tolerant to strong light. However, the rate of photodamage to PSII, as monitored in the presence of chloramphenicol, was similar in all three transformant strains and in wild-type cells, suggesting that the overexpression of these ROS-scavenging enzymes might not protect PSII from photodamage but might protect the repair of PSII. Under strong light, intracellular levels of ROS fell significantly, and the synthesis de novo of proteins that are required for the repair of PSII, such as the D1 protein, was enhanced. Our observations suggest that overexpressed Fe-SOD and VktA might act synergistically to alleviate the photoinhibition of PSII by reducing intracellular levels of ROS, with resultant protection of the repair of PSII from oxidative inhibition. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email:

  18. Assessing the additive risks of PSII herbicide exposure to the Great Barrier Reef. (United States)

    Lewis, Stephen E; Schaffelke, Britta; Shaw, Melanie; Bainbridge, Zoë T; Rohde, Ken W; Kennedy, Karen; Davis, Aaron M; Masters, Bronwyn L; Devlin, Michelle J; Mueller, Jochen F; Brodie, Jon E


    Herbicide residues have been measured in the Great Barrier Reef lagoon at concentrations which have the potential to harm marine plant communities. Monitoring on the Great Barrier Reef lagoon following wet season discharge show that 80% of the time when herbicides are detected, more than one are present. These herbicides have been shown to act in an additive manner with regards to photosystem-II inhibition. In this study, the area of the Great Barrier Reef considered to be at risk from herbicides is compared when exposures are considered for each herbicide individually and also for herbicide mixtures. Two normalisation indices for herbicide mixtures were calculated based on current guidelines and PSII inhibition thresholds. The results show that the area of risk for most regions is greatly increased under the proposed additive PSII inhibition threshold and that the resilience of this important ecosystem could be reduced by exposure to these herbicides. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Myocardial reverse remodeling. (United States)

    Hellawell, Jennifer L; Margulies, Kenneth B


    Despite an extensive literature defining the mechanisms and significance of pathological myocardial remodeling, there has been no comprehensive review of the inverse process, often labeled reverse remodeling. Accordingly, the goal of this review is to overview the varied settings in which clinically significant reverse remodeling has been well documented. When available, we reviewed relevant randomized, controlled clinical trials, and meta-analyses with sufficient cardiac imaging data to permit conclusions about reverse remodeling. When these types of studies were not available, relevant case-control studies and case series that employed appropriate methodology were reviewed. Regression of pathological myocardial hypertrophy, chamber shape distortions, and dysfunction occurs in a wide variety of settings. Although reverse remodeling occurs spontaneously in some etiologies of myocardial dysfunction and failure, remodeling is more commonly observed in response to medical, device-based, or surgical therapies, including β-blockers, revascularization, cardiac resynchronization therapy, and valve surgery. Indeed, reverse remodeling following pathophysiologically targeted interventions helps validate that the targeted mechanisms are propelling and/or sustaining pathological remodeling. The diverse clinical settings in which reverse remodeling has been observed demonstrates that myocardial remodeling is bidirectional and occurs across the full spectrum of myocardial disease severity, duration, and etiology. Observations in several settings suggest that recovered hearts are not truly normal despite parallel improvements at organ, tissue, and cellular level. Nevertheless, the link between reverse remodeling and improved outcomes should inspire further research to better understand the mechanisms responsible for both reverse remodeling and persistent deviations from normalcy. © 2010 Blackwell Publishing Ltd.

  20. Deletion of CGLD1 Impairs PSII and Increases Singlet Oxygen Tolerance of Green Alga Chlamydomonas reinhardtii

    Directory of Open Access Journals (Sweden)

    Jiale Xing


    Full Text Available The green alga Chlamydomonas reinhardtii is a key model organism for studying photosynthesis and oxidative stress in unicellular eukaryotes. Using a forward genetics approach, we have identified and characterized a mutant x32, which lacks a predicted protein named CGLD1 (Conserved in Green Lineage and Diatom 1 in GreenCut2, under normal and stress conditions. We show that loss of CGLD1 resulted in minimal photoautotrophic growth and PSII activity in the organism. We observed reduced amount of PSII complex and core subunits in the x32 mutant based on blue-native (BN/PAGE and immunoblot analysis. Moreover, x32 exhibited increased sensitivity to high-light stress and altered tolerance to different reactive oxygenic species (ROS stress treatments, i.e., decreased resistance to H2O2/or tert-Butyl hydroperoxide (t-BOOH and increased tolerance to neutral red (NR and rose bengal (RB that induce the formation of singlet oxygen, respectively. Further analysis via quantitative real-time PCR (qRT-PCR indicated that the increased singlet-oxygen tolerance of x32 was largely correlated with up-regulated gene expression of glutathione-S-transferases (GST. The phenotypical and physiological implications revealed from our experiments highlight the important roles of CGLD1 in maintaining structure and function of PSII as well as in protection of Chlamydomonas under photo-oxidative stress conditions.

  1. Stomatin-like protein 2 is required for in vivo mitochondrial respiratory chain supercomplex formation and optimal cell function. (United States)

    Mitsopoulos, Panagiotis; Chang, Yu-Han; Wai, Timothy; König, Tim; Dunn, Stanley D; Langer, Thomas; Madrenas, Joaquín


    Stomatin-like protein 2 (SLP-2) is a mainly mitochondrial protein that is widely expressed and is highly conserved across evolution. We have previously shown that SLP-2 binds the mitochondrial lipid cardiolipin and interacts with prohibitin-1 and -2 to form specialized membrane microdomains in the mitochondrial inner membrane, which are associated with optimal mitochondrial respiration. To determine how SLP-2 functions, we performed bioenergetic analysis of primary T cells from T cell-selective Slp-2 knockout mice under conditions that forced energy production to come almost exclusively from oxidative phosphorylation. These cells had a phenotype characterized by increased uncoupled mitochondrial respiration and decreased mitochondrial membrane potential. Since formation of mitochondrial respiratory chain supercomplexes (RCS) may correlate with more efficient electron transfer during oxidative phosphorylation, we hypothesized that the defect in mitochondrial respiration in SLP-2-deficient T cells was due to deficient RCS formation. We found that in the absence of SLP-2, T cells had decreased levels and activities of complex I-III2 and I-III2-IV(1-3) RCS but no defects in assembly of individual respiratory complexes. Impaired RCS formation in SLP-2-deficient T cells correlated with significantly delayed T cell proliferation in response to activation under conditions of limiting glycolysis. Altogether, our findings identify SLP-2 as a key regulator of the formation of RCS in vivo and show that these supercomplexes are required for optimal cell function. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Mitochondrial proteomic profile of complex IV deficiency fibroblasts: rearrangement of oxidative phosphorylation complex/supercomplex and other metabolic pathways. (United States)

    Salvador-Severo, Karina; Gómez-Caudillo, Leopoldo; Quezada, Héctor; García-Trejo, José de Jesús; Cárdenas-Conejo, Alan; Vázquez-Memije, Martha Elisa; Minauro-Sanmiguel, Fernando

    Mitochondriopathies are multisystem diseases affecting the oxidative phosphorylation (OXPHOS) system. Skin fibroblasts are a good model for the study of these diseases. Fibroblasts with a complex IV mitochondriopathy were used to determine the molecular mechanism and the main affected functions in this disease. Skin fibroblast were grown to assure disease phenotype. Mitochondria were isolated from these cells and their proteome extracted for protein identification. Identified proteins were validated with the MitoMiner database. Disease phenotype was corroborated on skin fibroblasts, which presented a complex IV defect. The mitochondrial proteome of these cells showed that the most affected proteins belonged to the OXPHOS system, mainly to the complexes that form supercomplexes or respirosomes (I, III, IV, and V). Defects in complex IV seemed to be due to assembly issues, which might prevent supercomplexes formation and efficient substrate channeling. It was also found that this mitochondriopathy affects other processes that are related to DNA genetic information flow (replication, transcription, and translation) as well as beta oxidation and tricarboxylic acid cycle. These data, as a whole, could be used for the better stratification of these diseases, as well as to optimize management and treatment options. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  3. Stoichiometric relationship between the (Mn){sub 4}-cluster and PSII Ca{sup 2+} necessary for O{sub 2}-evolution. Final report

    Energy Technology Data Exchange (ETDEWEB)



    This report focuses on the following research accomplishments: Stoichiometric relationship between the (Mn){sub 4}-cluster and PSII Ca{sup 2+} necessary for O{sub 2}-evolution; Photodamage of Mn-depleted PSII membranes: Sites and mechanisms of photoinactivation of primary reactions; The photoassembly of the PSII (Mn){sub 4}cluster is modulated by Ca{sup 2+} and DCIP; The natural product sorgoleone inhibits electron transfer at the Q{sub A}/Q{sub B} site of PSII; and Photodamages of Ca{sup 2+}-depleted PSII membranes: Sites and mechanisms of inactivation of donor side reactions.

  4. Solar UV-B effects on PSII performance in Betula nana are influenced by PAR level and reduced by EDU

    DEFF Research Database (Denmark)

    Albert, Kristian Rost; Mikkelsen, Teis Nørgaard; Ro-Poulsen, Helge


    The long-term and diurnal responses of photosystem II (PSII) performance to near-ambient UV-B radiation were investigated in High Arctic Betula nana. We conducted an UV exclusion experiment with five replicated blocks consisting of open control (no filter), photosynthetic active radiation and UV...... the effects of UV-B. Chlorophyll-a fluorescence induction curves were used for analysis of OJIP test parameters. Near-ambient UV-B radiation reduced across season maximum quantum yield (TRo /ABS = Fv /Fm ), approximated number of active PSII reaction center (RC/ABS) and the performance index (PIABS ), despite...... in reduced UV-B compared to near-ambient UV-B. This demonstrates current solar UV-B to reduce the PSII performance both on a daily as well as a seasonal basis in this High Arctic species....

  5. Antagonism between elevated CO2, nighttime warming, and summer drought reduces the robustness of PSII performance to freezing events

    DEFF Research Database (Denmark)

    Albert, Kristian Rost; Boesgaard, Kristine Stove; Ro-Poulsen, Helge


    out in the CLIMAITE multifactor experiment, which includes the combined impact of elevated CO2 (free air carbon enrichment; CO2), warming (passive nighttime warming; T) and summer drought (rain-excluding curtains; D) in a temperate heath ecosystem. PSII performance was probed by the effective quantum...... in the wavy hair-grass, Deschampsia flexuosa, and in the evergreen dwarf shrub common heather, Calluna vulgaris, and following freezing events the PItotal and Fv′/Fm′ were reduced even more. Contrary to expected, indirect effects of the previous summer drought reduced PSII performance before freezing events......, particularly in Calluna. In combinations with elevated CO2 interactive effects with drought, D×CO2 and warming, T×D×CO2, were negatively skewed and caused the reduction of PSII performance in both species after occurrence of freezing events. Neither passive nighttime warming nor elevated CO2 as single factors...

  6. Variations in morphology and PSII photosynthetic capabilities during the early development of tetraspores of Gracilaria vermiculophylla (Ohmi) Papenfuss (Gracilariales, Rhodophyta). (United States)

    Xie, Xiujun; Wang, Guangce; Pan, Guanghua; Gao, Shan; Xu, Pu; Zhu, Jianyi


    Red algae are primitive photosynthetic eukaryotes, whose spores are ideal subjects for studies of photosynthesis and development. Although the development of red alga spores has received considerable research attention, few studies have focused on the detailed morphological and photosynthetic changes that occur during the early development of tetraspores of Gracilaria vermiculophylla (Ohmi) Papenfuss (Gracilariales, Rhodophyta). Herein, we documented these changes in this species of red algae. In the tetraspores, we observed two types of division, cruciate and zonate, and both could develop into multicellular bodies (disks). During the first 84 hours, tetraspores divided several times, but the diameter of the disks changed very little; thereafter, the diameter increased significantly. Scanning electron microscopy observations and analysis of histological sections revealed that the natural shape of the disk remains tapered over time, and the erect frond grows from the central protrusion of the disk. Cultivation of tissue from excised disks demonstrated that the central protrusion of the disk is essential for initiation of the erect frond. Photosynthetic (i.e., PSII) activities were measured using chlorophyll fluorescence analysis. The results indicated that freshly released tetraspores retained limited PSII photosynthetic capabilities; when the tetraspores attached to a substrate, those capabilities increased significantly. In the disk, the PSII activity of both marginal and central cells was similar, although some degree of morphological polarity was present; the PSII photosynthetic capabilities in young germling exhibited an apico-basal gradient. Attachment of tetraspores to a substrate significantly enhanced their PSII photosynthetic capabilities, and triggered further development. The central protrusion of the disk is the growth point, may have transfer of nutritive material with the marginal cells. Within the young germling, the hetero-distribution of PSII

  7. Variations in morphology and PSII photosynthetic capabilities during the early development of tetraspores of Gracilaria vermiculophylla (Ohmi Papenfuss (Gracilariales, Rhodophyta

    Directory of Open Access Journals (Sweden)

    Gao Shan


    Full Text Available Abstract Background Red algae are primitive photosynthetic eukaryotes, whose spores are ideal subjects for studies of photosynthesis and development. Although the development of red alga spores has received considerable research attention, few studies have focused on the detailed morphological and photosynthetic changes that occur during the early development of tetraspores of Gracilaria vermiculophylla (Ohmi Papenfuss (Gracilariales, Rhodophyta. Herein, we documented these changes in this species of red algae. Results In the tetraspores, we observed two types of division, cruciate and zonate, and both could develop into multicellular bodies (disks. During the first 84 hours, tetraspores divided several times, but the diameter of the disks changed very little; thereafter, the diameter increased significantly. Scanning electron microscopy observations and analysis of histological sections revealed that the natural shape of the disk remains tapered over time, and the erect frond grows from the central protrusion of the disk. Cultivation of tissue from excised disks demonstrated that the central protrusion of the disk is essential for initiation of the erect frond. Photosynthetic (i.e., PSII activities were measured using chlorophyll fluorescence analysis. The results indicated that freshly released tetraspores retained limited PSII photosynthetic capabilities; when the tetraspores attached to a substrate, those capabilities increased significantly. In the disk, the PSII activity of both marginal and central cells was similar, although some degree of morphological polarity was present; the PSII photosynthetic capabilities in young germling exhibited an apico-basal gradient. Conclusions Attachment of tetraspores to a substrate significantly enhanced their PSII photosynthetic capabilities, and triggered further development. The central protrusion of the disk is the growth point, may have transfer of nutritive material with the marginal cells. Within

  8. Structure of PSI, PSII and antennae complexes from yellow-green alga Xanthonema debile. (United States)

    Gardian, Zdenko; Tichý, Josef; Vácha, František


    Photosynthetic carbon fixation by Chromophytes is one of the significant components of a carbon cycle on the Earth. Their photosynthetic apparatus is different in pigment composition from that of green plants and algae. In this work we report structural maps of photosystem I, photosystem II and light harvesting antenna complexes isolated from a soil chromophytic alga Xanthonema debile (class Xanthophyceae). Electron microscopy of negatively stained preparations followed by single particle analysis revealed that the overall structure of Xanthophytes' PSI and PSII complexes is similar to that known from higher plants or algae. Averaged top-view projections of Xanthophytes' light harvesting antenna complexes (XLH) showed two groups of particles. Smaller ones that correspond to a trimeric form of XLH, bigger particles resemble higher oligomeric form of XLH.

  9. Ambient UV-B radiation reduces PSII performance and net photosynthesis in high Arctic Salix arctica

    DEFF Research Database (Denmark)

    Albert, Kristian Rost; Mikkelsen, Teis Nørgaard; Ro-Poulsen, H.


    Ambient ultraviolet-B (UV-B) radiation potentially impacts the photosynthetic performance of high Arctic plants. We conducted an UV-B exclusion experiment in a dwarf shrub heath in NE Greenland (74°N), with open control, filter control, UV-B filtering and UV-AB filtering, all in combination...... was characterized by simultaneous gas exchange and chlorophyll fluorescence measurements and the PSII performance through the growing season was investigated with fluorescence measurements. Leaf harvest towards the end of the growing season was done to determine the specific leaf area and the content of carbon......, nitrogen and UV-B absorbing compounds. Compared to a 60% reduced UV-B irradiance, the ambient solar UV-B reduced net photosynthesis in Salix arctica leaves fixed in the 45° position which exposed leaves to maximum natural irradiance. Also a reduced Calvin Cycle capacity was found, i.e. the maximum rate...

  10. Effect of leaf dehydration duration and dehydration degree on PSII photochemical activity of papaya leaves. (United States)

    Liu, Meijun; Zhang, Zishan; Gao, Huiyuan; Yang, Cheng; Fan, Xingli; Cheng, Dandan


    Although the effect of dehydration on photosynthetic apparatus has been widely studied, the respective effect of dehydration duration and dehydration degree was neglected. This study showed that, when leaves dehydrated in air, the PSII activities of leaves decreased with the decline of leaf relative water content (RWC). Unexpectedly, when leaves dehydrated to same RWC, the decreases in Fv/Fm, Ψo and RC/CSm were lower in leaves dehydrating at 43 °C than those at 25 °C. However, to reach the same RWC, leaves dehydrating at 43 °C experienced 1/6 of the dehydration duration for leaves dehydrating at 25 °C. To distinguish the respective effect of dehydration degree and dehydration duration on photosynthetic apparatus, we studied the PSII activities of leaves treated with different concentration of PEG solutions. Increasing dehydration degree aggravated the decline of Fv/Fm, Ψo and RC/CSm in leaves with the same dehydration duration, while prolonging the dehydration duration also exacerbated the decline of Fv/Fm, Ψo and RC/CSm in leaves with identical dehydration degree. With the same dehydration degree and duration, high temperature enhanced the decrease of Fv/Fm, Ψo and RC/CSm in the leaves. When leaves dehydrated in air, the effect of high temperature was underestimated due to reduction of dehydration duration. The results demonstrated that, dehydration degree and duration both play important roles in damage to photosynthetic apparatus. We suggest that, under combined stresses, the effects of dehydration degree and duration on plants should be considered comprehensively, otherwise, partial or incorrect results may be obtained. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. The molecular structure of the IsiA-Photosystem I supercomplex, modelled from high-resolution, crystal structures of Photosystem I and the CP43 protein. (United States)

    Zhang, Yinan; Chen, Min; Church, W Bret; Lau, Kwok Wai; Larkum, Anthony W D; Jermiin, Lars S


    We present the molecular structure of the IsiA-Photosystem I (PSI) supercomplex, inferred from high-resolution, crystal structures of PSI and the CP43 protein. The structure of iron-stress-induced A protein (IsiA) is similar to that of CP43, albeit with the difference that IsiA is associated with 15 chlorophylls (Chls), one more than previously assumed. The membrane-spanning helices of IsiA contain hydrophilic residues many of which bind Chl. The optimal structure of the IsiA-PSI supercomplex was inferred by systematically rearranging the IsiA monomers and PSI trimer in relation to each other. For each of the 6,969,600 structural configurations considered, we counted the number of optimal Chl-Chl connections (i.e., cases where Chl-bound Mg atoms are 228% the energy-transfer potential. In conclusion, our model allows us to explain how the IsiA-PSI supercomplex may act as an efficient light-harvesting structure under low-light conditions and as an efficient dissipater of excess energy under high-light conditions.

  12. An integrated overview of spatiotemporal organization and regulation in mitosis in terms of the proteins in the functional supercomplexes

    Directory of Open Access Journals (Sweden)

    Yueyuan eZheng


    Full Text Available Eukaryotic cells may divide via the critical cellular process of cell division/mitosis, resulting in two daughter cells with the same genetic information. A large number of dedicated proteins are involved in this process and spatiotemporally assembled into three distinct super-complex structures/organelles, including the centrosome/spindle pole body, kinetochore/centromere and cleavage furrow/midbody/bud neck, so as to precisely modulate the cell division/mitosis events of chromosome alignment, chromosome segregation and cytokinesis in an orderly fashion. In recent years, many efforts have been made to identify the protein components and architecture of these subcellular organelles, aiming to uncover the organelle assembly pathways, determine the molecular mechanisms underlying the organelle functions, and thereby provide new therapeutic strategies for a variety of diseases. However, the organelles are highly dynamic structures, making it difficult to identify the entire components. Here, we review the current knowledge of the identified protein components governing the organization and functioning of organelles, especially in human and yeast cells, and discuss the multi-localized protein components mediating the communication between organelles during cell division.

  13. Chromatin remodeling in mammalian embryos. (United States)

    Cabot, Birgit; Cabot, Ryan A


    The mammalian embryo undergoes a dramatic amount of epigenetic remodeling during the first week of development. In this review, we discuss several epigenetic changes that happen over the course of cleavage development, focusing on covalent marks (e.g., histone methylation and acetylation) and non-covalent remodeling (chromatin remodeling via remodeling complexes; e.g., SWI/SNF-mediated chromatin remodeling). Comparisons are also drawn between remodeling events that occur in embryos from a variety of mammalian species. © 2018 Society for Reproduction and Fertility.

  14. Temperature-sensitive PSII: a novel approach for sustained photosynthetic hydrogen production. (United States)

    Bayro-Kaiser, Vinzenz; Nelson, Nathan


    The need for energy and the associated burden are ever growing. It is crucial to develop new technologies for generating clean and efficient energy for society to avoid upcoming energetic and environmental crises. Sunlight is the most abundant source of energy on the planet. Consequently, it has captured our interest. Certain microalgae possess the ability to capture solar energy and transfer it to the energy carrier, H2. H2 is a valuable fuel, because its combustion produces only one by-product: water. However, the establishment of an efficient biophotolytic H2 production system is hindered by three main obstacles: (1) the hydrogen-evolving enzyme, [FeFe]-hydrogenase, is highly sensitive to oxygen; (2) energy conversion efficiencies are not economically viable; and (3) hydrogen-producing organisms are sensitive to stressful conditions in large-scale production systems. This study aimed to circumvent the oxygen sensitivity of this process with a cyclic hydrogen production system. This approach required a mutant that responded to high temperatures by reducing oxygen evolution. To that end, we randomly mutagenized the green microalgae, Chlamydomonas reinhardtii, to generate mutants that exhibited temperature-sensitive photoautotrophic growth. The selected mutants were further characterized by their ability to evolve oxygen and hydrogen at 25 and 37 °C. We identified four candidate mutants for this project. We characterized these mutants with PSII fluorescence, P700 absorbance, and immunoblotting analyses. Finally, we demonstrated that these mutants could function in a prototype hydrogen-producing bioreactor. These mutant microalgae represent a novel approach for sustained hydrogen production.

  15. Remodeling Grounded Theory

    Directory of Open Access Journals (Sweden)

    Barney G. Glaser Ph.D., Hon. Ph.D.


    Full Text Available This paper outlines my concerns with Qualitative Data Analysis’ (QDAnumerous remodelings of Grounded Theory (GT and the subsequent eroding impact. I cite several examples of the erosion and summarize essential elements of classic GT methodology. It is hoped that the article will clarify my concerns with the continuing enthusiasm but misunderstood embrace of GT by QDA methodologists and serve as a preliminary guide to novice researchers who wish to explore the fundamental principles of GT.

  16. Vascular remodelling in asthma. (United States)

    Walters, Eugene Haydn; Soltani, Amir; Reid, David William; Ward, Chris


    We review the recent literature, focusing on 2006 and 2007, to produce an update on the patho-biology of angiogenesis and vascular endothelial growth factor in the asthmatic airway. In terms of conceptual development in asthma research, airway inflammation and remodelling have been regarded as separate processes or perhaps as sequential, with early inflammation leading later to remodelling. Recent insights identify a central role for vascular endothelial growth factor in stimulating both inflammation and vascular remodelling coincidentally, with the full panoply of vascular endothelial growth factor mediated events being complex and wide. Both nitric oxide and matrix metalloproteinase-9 induction may be important downstream pathogenic mechanisms. Virus-mediated exacerbations are a prime manifestation of the oscillating trajectory of clinical asthma. The early stimulation of vascular endothelial growth factor production is probably a central aetiological mechanism, with secondary inflammation and angiogenesis. The time scale of the latter, especially, fits with the time scale of clinico-physiological changes after exacerbation. These vascular endothelial growth factor induced changes are potentially modifiable with therapy. Insights into the importance of vascular endothelial growth factor and angiogenesis in asthma pathogenesis now lead to potential new therapeutic possibilities and elucidate why recent advances in asthma therapeutics have been so successful.

  17. Structural variability of plant photosystem II megacomplexes in thylakoid membranes

    NARCIS (Netherlands)

    Nosek, Lukáš; Semchonok, Dmitry; Boekema, Egbert J.; Ilík, Petr; Kouřil, Roman

    Plant photosystem II (PSII) is organized into large supercomplexes with variable amount of membrane-bound light-harvesting proteins (LHCII). The largest stable form of the PSII supercomplex involves four LHCII trimers, which are specifically connected to the PSII core dimer via monomeric antenna

  18. A structural investigation of complex I and I+III2 supercomplex from Zea mays at 11-13 angstrom resolution : Assignment of the carbonic anhydrase domain and evidence for structural heterogeneity within complex I

    NARCIS (Netherlands)

    Peters, Katrin; Dudkina, Natalya V.; Jaensch, Lothar; Braun, Hans-Peter; Boekema, Egbert J.; Jänsch, Lothar

    The projection structures of complex I and the I+III2 supercomplex from the C-4 plant Zea mays were determined by electron microscopy and single particle image analysis to a resolution of up to 11 angstrom. Maize complex I has a typical L-shape. Additionally, it has a large hydrophilic, extra-domain

  19. SUMO and Chromatin Remodeling. (United States)

    Wotton, David; Pemberton, Lucy F; Merrill-Schools, Jacqueline


    Many of the known SUMO substrates are nuclear proteins, which regulate gene expression and chromatin dynamics. Sumoylation, in general, appears to correlate with decreased transcriptional activity, and in many cases modulation of the chromatin template is implicated. Sumoylation of the core histones is associated with transcriptional silencing, and transcription factor sumoylation can decrease gene expression by promoting recruitment of chromatin modifying enzymes. Additionally, sumoylation of transcriptional corepressors and chromatin remodeling enzymes can influence interactions with other transcriptional regulators, and alter their enzymatic activity. In some cases, proteins that are components of transcriptional corepressor complexes have been shown to be SUMO E3 ligases, further emphasizing the integration of sumoylation with the regulation of chromatin remodeling. Despite the evidence suggesting that sumoylation is primarily repressive for access to chromatin, recent analyses suggest that protein sumoylation on the chromatin template may play important roles at highly expressed genes. Elucidating the dynamic interplay of sumoylation with other post-translational modifications of histones and chromatin associated proteins will be key to fully understanding the regulation of access to the chromatin template.

  20. Altered gene expression by sedaxane increases PSII efficiency, photosynthesis and growth and improves tolerance to drought in wheat seedlings. (United States)

    Ajigboye, Olubukola O; Lu, Chungui; Murchie, Erik H; Schlatter, Christian; Swart, Gina; Ray, Rumiana V


    Succinate dehydrogenase inhibitor (SDHI) fungicides have been shown to increase PSII efficiency and photosynthesis under drought stress in the absence of disease to enhance the biomass and yield of winter wheat. However, the molecular mechanism of improved photosynthetic efficiency observed in SDHI-treated wheat has not been previously elucidated. Here we used a combination of chlorophyll fluorescence, gas exchange and gene expression analysis, to aid our understanding of the basis of the physiological responses of wheat seedlings under drought conditions to sedaxane, a novel SDHI seed treatment. We show that sedaxane increased the efficiency of PSII photochemistry, reduced non-photochemical quenching and improved the photosynthesis and biomass in wheat correlating with systemic changes in the expression of genes involved in defense, chlorophyll synthesis and cell wall modification. We applied a coexpression network-based approach using differentially expressed genes of leaves, roots and pregerminated seeds from our wheat array datasets to identify the most important hub genes, with top ranked correlation (higher gene association value and z-score) involved in cell wall expansion and strengthening, wax and pigment biosynthesis and defense. The results indicate that sedaxane confers tolerant responses of wheat plants grown under drought conditions by redirecting metabolites from defense/stress responses towards growth and adaptive development. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Detection of herbicide effects on pigment composition and PSII photochemistry in Helianthus annuus by Raman spectroscopy and chlorophyll a fluorescence (United States)

    Vítek, Petr; Novotná, Kateřina; Hodaňová, Petra; Rapantová, Barbora; Klem, Karel


    The effects of herbicides from three mode-of-action groups - inhibitors of protoporphyrinogen oxidase (carfentrazone-ethyl), inhibitors of carotenoid biosynthesis (mesotrione, clomazone, and diflufenican), and inhibitors of acetolactate synthase (amidosulfuron) - were studied in sunflower plants (Helianthus annuus). Raman spectroscopy, chlorophyll fluorescence (ChlF) imaging, and UV screening of ChlF were combined to evaluate changes in pigment composition, photosystem II (PSII) photochemistry, and non-photochemical quenching in plant leaves 6 d after herbicide application. The Raman signals of phenolic compounds, carotenoids, and chlorophyll were evaluated and differences in their intensity ratios were observed. Strongly augmented relative content of phenolic compounds was observed in the case of amidosulfuron-treated plants, with a simultaneous decrease in the chlorophyll/carotenoid intensity ratio. The results were confirmed by in vivo measurement of flavonols using UV screening of ChlF. Herbicides from the group of carotenoid biosynthesis inhibitors significantly decreased both the maximum quantum efficiency of PSII and non-photochemical quenching as determined by ChlF. Resonance Raman imaging (mapping) data with high resolution (150,000-200,000 spectra) are presented, showing the distribution of carotenoids in H. annuus leaves treated by two of the herbicides acting as inhibitors of carotenoid biosynthesis (clomazone or diflufenican). Clear signs were observed that the treatment induced carotenoid depletion within sunflower leaves. The depletion spatial pattern registered differed depending on the type of herbicide applied.

  2. No-Regrets Remodeling, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)



    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  3. Cyclic electron flow may provide some protection against PSII photoinhibition in rice (Oryza sativa L.) leaves under heat stress. (United States)

    Essemine, Jemaa; Xiao, Yi; Qu, Mingnan; Mi, Hualing; Zhu, Xin-Guang


    Previously we have shown that a quick down-regulation in PSI activity compares to that of PSII following short-term heat stress for two rice groups including C4023 and Q4149, studied herein. These accessions were identified to have different natural capacities in driving cyclic electron flow (CEF) around PSI; i.e., low CEF (lcef) and high CEF (hcef) for C4023 and Q4149, respectively. The aim of this study was to investigate whether these two lines have different mechanisms of protecting photosystem II from photodamage under heat stress. We observed a stepwise alteration in the shape of Chl a fluorescence induction (OJIP) with increasing temperature treatment. The effect of 44°C treatment on the damping in Chl a fluorescence was more pronounced in C4023 than in Q4149. Likewise, we noted a disruption in the I-step, a decline in the Fv due to a strong damping in the Fm, and a slight increase in the F0. Normalized data demonstrated that the I-step seems more susceptible to 44°C in C4023 than in Q4149. We also measured the redox states of plastocyanin (PC) and P700 by monitoring the transmission changes at 820nm (I820), and observed a disturbance in the oxidation/reduction kinetics of PC and P700. The decline in the amplitude of their oxidation was shown to be about 29% and 13% for C4023 and Q4149, respectively. The electropotential component (Δφ) of ms-DLE appeared more sensitive to temperature stress than the chemical component (ΔpH), and the impact of heat was more evident and drastic in C4023 than in Q4149. Under heat stress, we noticed a concomitant decline in the primary photochemistry of PSII as well as in both the membrane energization process and the lumen protonation for both accessions, and it is evident that heat affects these parameters more in C4023 than in Q4149. All these data suggest that higher CET can confer higher photoprotection to PSII in rice lines, which can be a desirable trait during rice breeding, especially in the context of a "warming

  4. Structural variability of plant photosystem II megacomplexes in thylakoid membranes. (United States)

    Nosek, Lukáš; Semchonok, Dmitry; Boekema, Egbert J; Ilík, Petr; Kouřil, Roman


    Plant photosystem II (PSII) is organized into large supercomplexes with variable levels of membrane-bound light-harvesting proteins (LHCIIs). The largest stable form of the PSII supercomplex involves four LHCII trimers, which are specifically connected to the PSII core dimer via monomeric antenna proteins. The PSII supercomplexes can further interact in the thylakoid membrane, forming PSII megacomplexes. So far, only megacomplexes consisting of two PSII supercomplexes associated in parallel have been observed. Here we show that the forms of PSII megacomplexes can be much more variable. We performed single particle electron microscopy (EM) analysis of PSII megacomplexes isolated from Arabidopsis thaliana using clear-native polyacrylamide gel electrophoresis. Extensive image analysis of a large data set revealed that besides the known PSII megacomplexes, there are distinct groups of megacomplexes with non-parallel association of supercomplexes. In some of them, we have found additional LHCII trimers, which appear to stabilize the non-parallel assemblies. We also performed EM analysis of the PSII supercomplexes on the level of whole grana membranes and successfully identified several types of megacomplexes, including those with non-parallel supercomplexes, which strongly supports their natural origin. Our data demonstrate a remarkable ability of plant PSII to form various larger assemblies, which may control photochemical usage of absorbed light energy in plants in a changing environment. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  5. Merging Structural Information from X-ray Crystallography, Quantum Chemistry, and EXAFS Spectra: The Oxygen-Evolving Complex in PSII. (United States)

    Chernev, Petko; Zaharieva, Ivelina; Rossini, Emanuele; Galstyan, Artur; Dau, Holger; Knapp, Ernst-Walter


    Structural data of the oxygen-evolving complex (OEC) in photosystem II (PSII) determined by X-ray crystallography, quantum chemistry (QC), and extended X-ray absorption fine structure (EXAFS) analyses are presently inconsistent. Therefore, a detailed study of what information can be gained about the OEC through a comparison of QC and crystallographic structure information combined with the information from range-extended EXAFS spectra was undertaken. An analysis for determining the precision of the atomic coordinates of the OEC by QC is carried out. OEC model structures based on crystallographic data that are obtained by QC from different research groups are compared with one another and with structures obtained by high-resolution crystallography. The theory of EXAFS spectra is summarized, and the application of EXAFS spectra to the experimental determination of the structure of the OEC is detailed. We discriminate three types of parameters entering the formula for the EXAFS spectrum: (1) model-independent, predefined, and fixed; (2) model-dependent that can be computed or adjusted; and (3) model-dependent that must be adjusted. The information content of EXAFS spectra is estimated and is related to the precision of atomic coordinates and resolution power to discriminate different atom-pair distances of the OEC. It is demonstrated how a precise adjustment of atomic coordinates can yield a nearly perfect representation of the experimental OEC EXAFS spectrum, but at the expense of overfitting and losing the knowledge of the initial OEC model structure. Introducing a novel type of penalty function, it is shown that moderate adjustment of atomic coordinates to the EXAFS spectrum limited by constraints avoids overfitting and can be used to validate different OEC model structures. This technique is used to identify the OEC model structures whose computed OEC EXAFS spectra agree best with the measured spectrum. In this way, the most likely S-state and protonation pattern

  6. Supramolecular organization of photosystem II in green plants

    NARCIS (Netherlands)

    Kouril, Roman; Dekker, Jan P.; Boekema, Egbert J.; Kouřil, Roman

    Green plant photosystem II (PSII) is involved in the light reactions of photosynthesis, which take place in the thylakoid membrane of the chloroplast PSII is organized into large supercomplexes with variable amounts of membrane-bound peripheral antenna complexes. These supercomplexes are dimeric and

  7. Relationships between PSII-independent hydrogen bioproduction and starch metabolism as evidenced from isolation of starch catabolism mutants in the green alga Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Chochois, Vincent; Constans, Laure; Beyly, Audrey; Soliveres, Melanie; Peltier, Gilles; Cournac, Laurent [CEA, DSV, IBEB, Laboratoire de Bioenergetique et Biotechnologie des Bacteries and Microalgues, Saint Paul Lez Durance, F-13108 (France); CNRS, UMR Biologie Vegetale and Microbiologie Environnementales, Saint Paul lez Durance, F-13108 (France); Aix-Marseille Universite, Saint Paul lez Durance, F-13108 (France); Dauvillee, David; Ball, Steven [Univ Lille Nord de France, F-59000 Lille (France); USTL, UGSF, F-59650 Villeneuve d' Ascq (France); CNRS, UMR 8576, F-59650 Villeneuve d' Ascq (France)


    Sulfur deprivation, which is considered as an efficient way to trigger long-term hydrogen photoproduction in unicellular green algae has two major effects: a decrease in PSII which allows anaerobiosis to be reached and carbohydrate (starch) storage. Starch metabolism has been proposed as one of the major factors of hydrogen production, particularly during the PSII-independent (or indirect) pathway. While starch biosynthesis has been characterized in the green alga Chlamydomonas reinhardtii, little remains known concerning starch degradation. In order to gain a better understanding of starch catabolism pathways and identify those steps likely to limit the starch-dependent hydrogen production, we have designed a genetic screening procedure aimed at isolating mutants of the green alga C. reinhardtii affected in starch mobilization. Using two different screening protocols, the first one based on aerobic starch degradation in the dark and the second one on anaerobic starch degradation in the light, eighteen mutants were isolated among a library of 15,000 insertion mutants, eight (std1-8) with the first screen and ten (sda1-10) with the second. Most of the mutant strains isolated in this study showed a reduction or a delay in the PSII-independent hydrogen production. Further characterization of these mutants should allow the identification of molecular determinants of starch-dependent hydrogen production and supply targets for future biotechnological improvements. (author)

  8. Neural remodeling in retinal degeneration. (United States)

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica


    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  9. Chromatin remodeling in plant development. (United States)

    Jarillo, José A; Piñeiro, Manuel; Cubas, Pilar; Martínez-Zapater, José M


    Plant development results from specific patterns of gene expression that are tightly regulated in a spatio-temporal manner. Chromatin remodeling plays a central role in establishing these expression patterns and maintaining epigenetic transcriptional states through successive rounds of mitosis that take place within a cell lineage. Plant epigenetic switches occur not only at the embryo stage, but also during postembryonic developmental transitions, suggesting that chromatin remodeling activities in plants can provide a higher degree of regulatory flexibility which probably underlies their developmental plasticity. Here, we highlight recent progress in the understanding of plant chromatin dynamic organization, facilitating the activation or repression of specific sets of genes involved in different developmental programs and integrating them with the response to environmental signals. Chromatin conformation controls gene expression both in actively dividing undifferentiated cells and in those already fate-determined. In this context, we first describe chromatin reorganization activities required to maintain meristem function stable through DNA replication and cell division. Organ initiation at the apex, with emphasis on reproductive development, is next discussed to uncover the chromatin events involved in the establishment and maintenance of expression patterns associated with differentiating cells; this is illustrated with the complex epigenetic regulation of the Arabidopsis floral repressor FLOWERING LOCUS C (FLC). Finally, we discuss the involvement of chromatin remodeling in plant responses to environmental cues and to different types of stress conditions.

  10. Calcium remodeling in colorectal cancer. (United States)

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía


    Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca(2+) entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC. SOCE and store-operated currents (SOCs) are dramatically enhanced in CRC while Ca(2+) stores are partially empty in CRC cells. These features may contribute to CRC hallmarks including enhanced cell proliferation, migration, invasion and survival. At the molecular level, enhanced SOCE and depleted stores are mediated by overexpression of Orai1, Stromal interaction protein 1 (STIM1) and Transient receptor protein channel 1 (TRPC1) and downregulation of STIM2. In normal colonic cells, SOCE is mediated by Ca(2+)-release activated Ca(2+) channels made of STIM1, STIM2 and Orai1. In CRC cells, SOCE is mediated by different store-operated currents (SOCs) driven by STIM1, Orai1 and TRPC1. Loss of STIM2 contributes to depletion of Ca(2+) stores and enhanced resistance to cell death in CRC cells. Thus, SOCE is a novel key player in CRC and inhibition by salicylate and other NSAIDs may contribute to explain chemoprevention activity. Colorectal cancer (CRC) is the third most frequent form of cancer worldwide. Recent evidence suggests that intracellular Ca(2+) remodeling may contribute to cancer hallmarks. In addition, aspirin and other NSAIDs might prevent CRC acting on remodeled Ca(2+) entry pathways. In this review, we will briefly describe 1) the players involved in intracellular Ca(2+) homeostasis with a particular emphasis on the mechanisms involved in SOCE activation and inactivation, 2) the evidence that aspirin

  11. Pathophysiology of Vascular Remodeling in Hypertension

    Directory of Open Access Journals (Sweden)

    Nicolás F. Renna


    Full Text Available Vascular remodeling refers to alterations in the structure of resistance vessels contributing to elevated systemic vascular resistance in hypertension. We start with some historical aspects, underscoring the importance of Glagov’s contribution. We then move to some basic concepts on the biomechanics of blood vessels and explain the definitions proposed by Mulvany for specific forms of remodeling, especially inward eutrophic and inward hypertrophic. The available evidence for the existence of remodeled resistance vessels in hypertension comes next, with relatively more weight given to human, in comparison with animal data. Mechanisms are discussed. The impact of antihypertensive drug treatment on remodeling is described, again with emphasis on human data. Some details are given on the three mechanisms to date which point to remodeling resistance arteries as an independent predictor of cardiovascular risk in hypertensive patients. We terminate by considering the potential role of remodeling in the pathogenesis of endorgan damage and in the perpetuation of hypertension.

  12. Bone remodelling in inflammatory arthritis. (United States)

    Goldring, Steven R; Purdue, P Edward; Crotti, Tania N; Shen, Zhenxin; Flannery, Merrilee R; Binder, Nikolaus B; Ross, F Patrick; McHugh, Kevin P


    The inflammatory arthropathies that include rheumatoid arthritis, the seronegative spondyloarthropathies and systemic lupus erythematosus are characterised by marked alterations in the architecture and structural integrity of peri-articular bone; however, the pattern and natural history of the skeletal changes differs in these conditions. In part, this can be attributed to differences in the primary anatomical site of the inflammation, but also there is evidence that there are differences in the biological properties and products produced by inflammatory tissues. This review will focus on recent advances in the understanding of the cellular and molecular mechanisms that contribute to the differential pattern of articular bone remodelling in these prototypical inflammatory forms of arthritis.

  13. Adrenocortical zonation, renewal, and remodeling

    Directory of Open Access Journals (Sweden)

    Marjut ePihlajoki


    Full Text Available The adrenal cortex is divided into concentric zones. In humans the major cortical zones are the zona glomerulosa, zona fasciculata, and zona reticularis. The adrenal cortex is a dynamic organ in which senescent cells are replaced by newly differentiated ones. This constant renewal facilitates organ remodeling in response to physiological demand for steroids. Cortical zones can reversibly expand, contract, or alter their biochemical profiles to accommodate needs. Pools of stem/progenitor cells in the adrenal capsule, subcapsular region, and juxtamedullary region can differentiate to repopulate or expand zones. Some of these pools appear to be activated only during specific developmental windows or in response to extreme physiological demand. Senescent cells can also be replenished through direct lineage conversion; for example, cells in the zona glomerulosa can transform into cells of the zona fasciculata. Adrenocortical cell differentiation, renewal, and function are regulated by a variety of endocrine/paracrine factors including adrenocorticotropin, angiotensin II, insulin-related growth hormones, luteinizing hormone, activin, and inhibin. Additionally, zonation and regeneration of the adrenal cortex are controlled by developmental signaling pathways, such as the sonic hedgehog, delta-like homologue 1, fibroblast growth factor, and WNT/β-catenin pathways. The mechanisms involved in adrenocortical remodeling are complex and redundant so as to fulfill the offsetting goals of organ homeostasis and stress adaptation.

  14. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst


    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  15. Exercise training in adverse cardiac remodeling. (United States)

    Duncker, Dirk J; van Deel, Elza D; de Waard, Monique C; de Boer, Martine; Merkus, Daphne; van der Velden, Jolanda


    Cardiac remodeling in response to a myocardial infarction or chronic pressure-overload is an independent risk factor for the development of heart failure. In contrast, cardiac remodeling produced by regular physical exercise is associated with a decreased risk for heart failure. There is evidence that exercise training has a beneficial effect on disease progression and survival in patients with cardiac remodeling and dysfunction, but concern has also been expressed that exercise training may aggravate pathological remodeling and dysfunction. Here we present studies from our laboratory into the effects of exercise training on pathological cardiac remodeling and dysfunction in mice. The results indicate that even in the presence of a large infarct, exercise training exerts beneficial effects on the heart. These effects were mimicked in part by endothelial nitric oxide synthase (eNOS) overexpression and abrogated by eNOS deficiency, demonstrating the importance of nitric oxide signaling in mediating the cardiac effects of exercise. Exercise prior to a myocardial infarction was also cardioprotective. In contrast, exercise tended to aggravate pathological cardiac remodeling and dysfunction in the setting of pressure-overload produced by an aortic stenosis. These observations emphasize the critical importance of the underlying pathological stimulus for cardiac hypertrophy and remodeling, in determining the effects of exercise training. Future studies are needed to define the influence of exercise type, intensity and duration in different models and severities of pathological cardiac remodeling. Together such studies will aid in optimizing the therapy of exercise training in the setting of cardiovascular disease.

  16. RV Remodeling in Olympic Athletes. (United States)

    D'Ascenzi, Flavio; Pisicchio, Cataldo; Caselli, Stefano; Di Paolo, Fernando M; Spataro, Antonio; Pelliccia, Antonio


    The aim of this study was to assess the impact of sex and different sports on right ventricular (RV) remodeling and compare the derived upper limits with widely used revised Task Force (TF) reference values. Uncertainties exist regarding the extent and physiological determinants of RV remodeling in highly trained athletes. The issue is important, considering that in athletes RV size occasionally exceeds the cutoff limits proposed to diagnose arrhythmogenic RV cardiomyopathy. A total of 1,009 Olympic athletes (mean age 24 ± 6 years; n = 647 [64%] males) participating in skill, power, mixed, and endurance sport were evaluated by 2-dimensional echocardiography and Doppler/tissue Doppler imaging. The right ventricular outflow tract (RVOT) in parasternal long-axis (PLAX) and short-axis views, fractional area change, s' velocity, and morphological features were assessed. Indexed RVOT PLAX was greater in females than in males (15.3 ± 2.2 mm/m2 vs. 14.4 ± 1.9 mm/m2; p view were significantly different among skill, power, mixed, and endurance sports: 14.3 ± 2.1 mm/m2 versus 14.7 ± 1.9 mm/m2 versus 14.0 ± 1.8 mm/m2 versus 15.7 ± 2.2 mm/m2, respectively (p view was 18 mm/m2 and 20 mm/m2, respectively. Fractional area change and s' velocity did not differ among the groups (p = 0.34 for both). RV enlargement compatible with major and minor TF diagnostic criteria for arrhythmogenic RV cardiomyopathy was observed in 41 (4%) and 319 (32%) athletes. A rounded apex was described in 823 (81%) athletes, prominent trabeculations in 378 (37%) athletes, and a prominent/hyperreflective moderator band in 5 (0.5%) athletes. RV remodeling occurs in Olympic athletes, with male sex and endurance practice playing the major impact. A significant subset (up to 32%) of athletes exceeds the normal TF limits; therefore, we recommend referring to the 95th percentiles here reported as referral values; alternatively, only major diagnostic TF criteria for arrhythmogenic RV cardiomyopathy

  17. C lostridium difficile surface proteins are anchored to the cell wall using CWB2 motifs that recognise the anionic polymer PSII (United States)

    Willing, Stephanie E.; Candela, Thomas; Shaw, Helen Alexandra; Seager, Zoe; Mesnage, Stéphane; Fagan, Robert P.


    Summary Gram‐positive surface proteins can be covalently or non‐covalently anchored to the cell wall and can impart important properties on the bacterium in respect of cell envelope organisation and interaction with the environment. We describe here a mechanism of protein anchoring involving tandem CWB2 motifs found in a large number of cell wall proteins in the Firmicutes. In the Clostridium difficile cell wall protein family, we show the three tandem repeats of the CWB2 motif are essential for correct anchoring to the cell wall. CWB2 repeats are non‐identical and cannot substitute for each other, as shown by the secretion into the culture supernatant of proteins containing variations in the patterns of repeats. A conserved Ile Leu Leu sequence within the CWB2 repeats is essential for correct anchoring, although a preceding proline residue is dispensable. We propose a likely genetic locus encoding synthesis of the anionic polymer PSII and, using RNA knock‐down of key genes, reveal subtle effects on cell wall composition. We show that the anionic polymer PSII binds two cell wall proteins, SlpA and Cwp2, and these interactions require the CWB2 repeats, defining a new mechanism of protein anchoring in Gram‐positive bacteria. PMID:25649385

  18. Obesity and carotid artery remodeling

    DEFF Research Database (Denmark)

    Kozakova, M; Palombo, C; Morizzo, C


    BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions...... and CCA LD (266 healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects...... without CV complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile...

  19. ISWI chromatin remodellers sense nucleosome modifications to determine substrate preference

    DEFF Research Database (Denmark)

    Dann, Geoffrey P; Liszczak, Glen P; Bagert, John D


    ATP-dependent chromatin remodellers regulate access to genetic information by controlling nucleosome positions in vivo. However, the mechanism by which remodellers discriminate between different nucleosome substrates is poorly understood. Many chromatin remodelling proteins possess conserved...... activity of all ISWI remodellers evaluated. This dependence also extends to CHD and SWI/SNF family remodellers, suggesting that the acidic patch may be generally required for chromatin remodelling. Critically, remodelling activity can be regulated by modifications neighbouring the acidic patch, signifying...... that it may act as a tunable interaction hotspot for ATP-dependent chromatin remodellers and, by extension, many other chromatin effectors that engage this region of the nucleosome surface....

  20. Maternal uterine vascular remodeling during pregnancy. (United States)

    Osol, George; Mandala, Maurizio


    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

  1. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian


    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  2. Mutational remodeling of enzyme specificity. (United States)

    Bone, R; Agard, D A


    With the advent of genetic engineering techniques has come the ability to modify proteins as desired. Given this stunning capability, the question remains what residues should be altered, and how should they be changed to achieve a particular specificity pattern. The goals of such modifications are likely to fall into either of two categories: probing the function of a protein or attempting to alter its properties. In either case, our understanding of the consequences of a mutation, as ascertained by our ability to predict the results, is currently quite limited. The problem is extraordinarily complex; our understanding of how to calculate the energetics involved is still incomplete, and we are just beginning to accumulate experimental data which may help guide us. On the positive side, theoretical methods are now being developed and refined that should prove useful in the drive to engineer enzyme specificity. What may be most important at this juncture is to expand the experimental database interrelating sequence, function, and structure. That is, there should be a concerted effort to combine functional analysis of mutant proteins with structural analysis. Only from this combined examination of the effects of mutations can sufficient data be accumulated to test and improve both qualitative and quantitative approaches or methods for remodeling enzyme specificity.

  3. Lead Poisoning in Remodeling of Old Homes (United States)

    Barnes, Bart


    An article based on Dr. Muriel D. Wolf's study of elevated blood lead levels in children and adults present during the remodeling of old homes. Lead poisoning examples, symptoms, and precautions are given. (ST)

  4. Transcriptional networks and chromatin remodeling controlling adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; Mandrup, Susanne


    remodeling have revealed 'snapshots' of this cascade and the chromatin landscape at specific time-points of differentiation. These studies demonstrate that multiple adipogenic transcription factors co-occupy hotspots characterized by an open chromatin structure and specific epigenetic modifications...

  5. Influence of temperature on properties of nitrogen plasma source ion implantation (N-PSII) of Ti6A14V alloy

    CERN Document Server

    Geng Man; Zhao Qing


    Specimens of Ti6Al4V alloy were implanted with nitrogen plasma source ion implantation (N-PSII) at temperatures between 100 degree C and 600 degree C to a ion dose of 4 x 10 sup 1 sup 7 cm sup - sup 2. Auger Electron Spectroscopy (AES) was used to determine the nitrogen concentration depth profiles. Microhardness measurements and pin-on-disk wear test were performed to evaluate the improvements of the surface modification. Glancing angle X-ray diffraction (XRD) was employed to determine the phases presented in the surface modified layer. The thickness of implanted layer increased by about an order of magnitude when the temperature was elevated from 100 degree C to 600 degree C. Higher surface hardness and wear resistance was also obtained at higher temperature. Scanning electron microscopy (SEM) showed distinct microstructural changes and the presence of titanium nitrides in the implanted surface

  6. Estimating chlorophyll content and photochemical yield of photosystem II (ΦPSII) using solar-induced chlorophyll fluorescence measurements at different growing stages of attached leaves. (United States)

    Tubuxin, Bayaer; Rahimzadeh-Bajgiran, Parinaz; Ginnan, Yusaku; Hosoi, Fumiki; Omasa, Kenji


    This paper illustrates the possibility of measuring chlorophyll (Chl) content and Chl fluorescence parameters by the solar-induced Chl fluorescence (SIF) method using the Fraunhofer line depth (FLD) principle, and compares the results with the standard measurement methods. A high-spectral resolution HR2000+ and an ordinary USB4000 spectrometer were used to measure leaf reflectance under solar and artificial light, respectively, to estimate Chl fluorescence. Using leaves of Capsicum annuum cv. 'Sven' (paprika), the relationships between the Chl content and the steady-state Chl fluorescence near oxygen absorption bands of O2B (686nm) and O2A (760nm), measured under artificial and solar light at different growing stages of leaves, were evaluated. The Chl fluorescence yields of ΦF 686nm/ΦF 760nm ratios obtained from both methods correlated well with the Chl content (steady-state solar light: R(2) = 0.73; artificial light: R(2) = 0.94). The SIF method was less accurate for Chl content estimation when Chl content was high. The steady-state solar-induced Chl fluorescence yield ratio correlated very well with the artificial-light-induced one (R(2) = 0.84). A new methodology is then presented to estimate photochemical yield of photosystem II (ΦPSII) from the SIF measurements, which was verified against the standard Chl fluorescence measurement method (pulse-amplitude modulated method). The high coefficient of determination (R(2) = 0.74) between the ΦPSII of the two methods shows that photosynthesis process parameters can be successfully estimated using the presented methodology. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  7. Dynamics of the ethanolamine glycerophospholipid remodeling network.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    Full Text Available Acyl chain remodeling in lipids is a critical biochemical process that plays a central role in disease. However, remodeling remains poorly understood, despite massive increases in lipidomic data. In this work, we determine the dynamic network of ethanolamine glycerophospholipid (PE remodeling, using data from pulse-chase experiments and a novel bioinformatic network inference approach. The model uses a set of ordinary differential equations based on the assumptions that (1 sn1 and sn2 acyl positions are independently remodeled; (2 remodeling reaction rates are constant over time; and (3 acyl donor concentrations are constant. We use a novel fast and accurate two-step algorithm to automatically infer model parameters and their values. This is the first such method applicable to dynamic phospholipid lipidomic data. Our inference procedure closely fits experimental measurements and shows strong cross-validation across six independent experiments with distinct deuterium-labeled PE precursors, demonstrating the validity of our assumptions. In contrast, fits of randomized data or fits using random model parameters are worse. A key outcome is that we are able to robustly distinguish deacylation and reacylation kinetics of individual acyl chain types at the sn1 and sn2 positions, explaining the established prevalence of saturated and unsaturated chains in the respective positions. The present study thus demonstrates that dynamic acyl chain remodeling processes can be reliably determined from dynamic lipidomic data.

  8. Adipose tissue remodeling in pathophysiology of obesity. (United States)

    Lee, Mi-Jeong; Wu, Yuanyuan; Fried, Susan K


    Recent studies demonstrate that adipose tissue undergoes a continuous process of remodeling that is pathologically accelerated in the obese state. Contrary to earlier dogma, adipocytes die and are replaced by newly differentiated ones. This review will summarize recent advances of our knowledge of the mechanisms that regulate adipose tissue remodeling and highlight the influences of obesity, depot, and sex, as well as the relevance of rodent models to humans. A substantial literature now points to the importance of dynamic changes in adipocyte and immune cell turnover, angiogenesis, and extracellular matrix remodeling in regulating the expandability and functional integrity of this tissue. In obesity, the macrophages are recruited, surrounding dead adipocytes and polarized toward an inflammatory phenotype. The number of dead adipocytes is closely associated with the pathophysiological consequences of obesity, including insulin resistance and hepatic steatosis. Further, there are substantial depot, sex and species differences in the extent of remodeling. Adipose tissue undergoes a continuous remodeling process that normally maintains tissue health, but may spin out of control and lead to adipocyte death in association with the recruitment and activation of macrophages, and systemic insulin resistance.

  9. Bone remodeling as a spatial evolutionary game. (United States)

    Ryser, Marc D; Murgas, Kevin A


    Bone remodeling is a complex process involving cell-cell interactions, biochemical signaling and mechanical stimuli. Early models of the biological aspects of remodeling were non-spatial and focused on the local dynamics at a fixed location in the bone. Several spatial extensions of these models have been proposed, but they generally suffer from two limitations: first, they are not amenable to analysis and are computationally expensive, and second, they neglect the role played by bone-embedded osteocytes. To address these issues, we developed a novel model of spatial remodeling based on the principles of evolutionary game theory. The analytically tractable framework describes the spatial interactions between zones of bone resorption, bone formation and quiescent bone, and explicitly accounts for regulation of remodeling by bone-embedded, mechanotransducing osteocytes. Using tools from the theory of interacting particle systems we systematically classified the different dynamic regimes of the spatial model and identified regions of parameter space that allow for global coexistence of resorption, formation and quiescence, as observed in physiological remodeling. In coexistence scenarios, three-dimensional simulations revealed the emergence of sponge-like bone clusters. Comparison between spatial and non-spatial dynamics revealed substantial differences and suggested a stabilizing role of space. Our findings emphasize the importance of accounting for spatial structure and bone-embedded osteocytes when modeling the process of bone remodeling. Thanks to the lattice-based framework, the proposed model can easily be coupled to a mechanical model of bone loading. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Biomechanical Remodeling of the Diabetic Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Liao, Donghua; Yang, Jian


    several years, several studies demonstrated that experimental diabetes induces GI morphological and biomechanical remodeling. Following the development of diabetes, the GI wall becomes thicker and the stiffness of the GI wall increases in a time-dependent manner. It is well known that mechanosensitive...... the biomechanical environment of the mechanosensitive nerve endings, therefore, the structure as well as the tension, stress and strain distribution in the GI wall is important for the sensory and motor function. Biomechanical remodeling of diabetic GI tract including alterations of residual strain and increase...

  11. Genetic backgrounds determine brown remodeling of white fat in rodents

    Directory of Open Access Journals (Sweden)

    Giulia Ferrannini


    Conclusion: Rodent genetic background determines the brown remodeling of different white fat depots. This study provides new insights into the role of genetic variation in fat remodeling in susceptibility to metabolic diseases.

  12. Strategies for Energy Efficient Remodeling: SEER 2003 Case Study Report

    Energy Technology Data Exchange (ETDEWEB)



    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance.

  13. Retinal remodeling in human retinitis pigmentosa. (United States)

    Jones, B W; Pfeiffer, R L; Ferrell, W D; Watt, C B; Marmor, M; Marc, R E


    Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A


    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

  15. Synapse remodeling, compliments of the complement system. (United States)

    Fourgeaud, Lawrence; Boulanger, Lisa M


    A growing body of evidence indicates that some proteins known for their immune functions also have distinct nonimmune functions in the normal uninjured central nervous system. In this issue, Stevens et al. (2007) demonstrate an unexpected requirement for molecules of the complement cascade in the remodeling of synaptic connections in the developing visual system.

  16. Bronchial Smooth Muscle Remodeling in Nonsevere Asthma. (United States)

    Girodet, Pierre-Olivier; Allard, Benoit; Thumerel, Matthieu; Begueret, Hugues; Dupin, Isabelle; Ousova, Olga; Lassalle, Régis; Maurat, Elise; Ozier, Annaig; Trian, Thomas; Marthan, Roger; Berger, Patrick


    Increased bronchial smooth muscle (BSM) mass is a key feature of airway remodeling that classically distinguishes severe from nonsevere asthma. Proliferation of BSM cells involves a specific mitochondria-dependent pathway in individuals with severe asthma. However, BSM remodeling and mitochondrial biogenesis have not been examined in nonsevere asthma. We aimed to assess whether an increase in BSM mass was also implicated in nonsevere asthma and its relationship with mitochondria and clinical outcomes. We enrolled 34 never-smoker subjects with nonsevere asthma. In addition, we recruited 56 subjects with nonsevere asthma and 19 subjects with severe asthma as comparative groups (COBRA cohort [Cohorte Obstruction Bronchique et Asthme; Bronchial Obstruction and Asthma Cohort; sponsored by the French National Institute of Health and Medical Research, INSERM]). A phenotypic characterization was performed using questionnaires, atopy and pulmonary function testing, exhaled nitric oxide measurement, and blood collection. Bronchial biopsy specimens were processed for immunohistochemistry and electron microscopy analysis. After BSM remodeling assessment, subjects were monitored over a 12-month period. We identified characteristic features of remodeling (BSM area >26.6%) and increased mitochondrial number within BSM in a subgroup of subjects with nonsevere asthma. The number of BSM mitochondria was positively correlated with BSM area (r = 0.78; P asthma with high BSM had worse asthma control and a higher rate of exacerbations per year compared with subjects with low BSM. This study reveals that BSM remodeling and mitochondrial biogenesis may play a critical role in the natural history of nonsevere asthma (Mitasthme study). Clinical trial registered with (NCT00808730).

  17. Correlated behavior of the EPR signal of cytochrome b-559 heme Fe(III) ligated by OH- and the multiline signal of the Mn cluster in PS-II membrane fragments. (United States)

    Fiege, R; Shuvalov, V A


    EPR signals of Cyt b-559 heme Fe(III) ligated by OH- and the multiline signal of the Mn cluster in PS-II membrane fragments have been investigated. In 2,3-dicyano-5,6-dichloro-p-benzoquinone-oxidized PS-II membrane fragments the light-induced decrease of the EPR signal of the heme Fe(III)-OH- is accompanied by the appearance of the EPR multiline signal of the Mn cluster. Addition of F- ions, which act as a stronger ligand for heme Fe(III) than OH-, decreases to the same extent the dark- and light-induced signal of the heme Fe(III)-OH- and the light-induced multiline signal of the Mn cluster. These results are discussed in terms of the light-induced formation of a bound OH' radical shared between the Cyt b-559 heme Fe and the Mn cluster as a first step of water oxidation.

  18. Improved UV-B screening capacity does not prevent negative effects of ambient UV irradiance on PSII performance in High Arctic plants. Results from a six year UV exclusion study

    DEFF Research Database (Denmark)

    Albert, Kristian Rost; Mikkelsen, Teis Nørgaard; Ro-Poulsen, H.


    Long-term responses of ambient solar ultraviolet (UV) radiation were investigated on Salix arctica and Vaccinium uliginosum in a High Arctic heath ecosystem in Zackenberg, northeast Greenland. Over a period of six years, UV exclusion was conducted in the growing season by means of filters: 60% UV......-B reduction, 90% UV-B + UV-A reduction, UV transparent filter control, and an open control without filter. Plant responses were evaluated using specific leaf area, leaf content of UV-B absorbing compounds and PSII performance parameters derived from chlorophyll-a fluorescence induction curves. Based...... increased TRo/ABS = FV/FM and REo/ETo. These results demonstrate the current level of ambient UV-B to decrease PSII performance significantly in these High Arctic plants. It appears that the two plant species both have improved their UV-screening capacity, but through different strategies, although this did...

  19. Intermittent pacing therapy favorably modulates infarct remodeling. (United States)

    Uitterdijk, André; Springeling, Tirza; Hermans, Kevin C M; Merkus, Daphne; de Beer, Vincent J; Gorsse-Bakker, Charlotte; Mokelke, Eric; Daskalopoulos, Evangelos P; Wielopolski, Piotr A; Cleutjens, Jack P M; Blankesteijn, W Matthijs; Prinzen, Frits W; van der Giessen, Willem J; van Geuns, Robert-Jan M; Duncker, Dirk J


    Despite early revascularization, remodeling and dysfunction of the left ventricle (LV) after acute myocardial infarction (AMI) remain important therapeutic targets. Intermittent pacing therapy (IPT) of the LV can limit infarct size, when applied during early reperfusion. However, the effects of IPT on post-AMI LV remodeling and infarct healing are unknown. We therefore investigated the effects of IPT on global LV remodeling and infarct geometry in swine with a 3-day old AMI. For this purpose, fifteen pigs underwent 2 h ligation of the left circumflex coronary artery followed by reperfusion. An epicardial pacing lead was implanted in the peri-infarct zone. After three days, global LV remodeling and infarct geometry were assessed using magnetic resonance imaging (MRI). Animals were stratified into MI control and IPT groups. Thirty-five days post-AMI, follow-up MRI was obtained and myofibroblast content, markers of extracellular matrix (ECM) turnover and Wnt/frizzled signaling in infarct and non-infarct control tissue were studied. Results showed that IPT had no significant effect on global LV remodeling, function or infarct mass, but modulated infarct healing. In MI control pigs, infarct mass reduction was principally due to a 26.2 ± 4.4% reduction in infarct thickness (P ≤ 0.05), whereas in IPT pigs it was mainly due to a 35.7 ± 4.5% decrease in the number of infarct segments (P ≤ 0.05), with no significant change in infarct thickness. Myofibroblast content of the infarct zone was higher in IPT (10.9 ± 2.1%) compared to MI control (5.4 ± 1.6%; P ≤ 0.05). Higher myofibroblast presence did not coincide with alterations in expression of genes involved in ECM turnover or Wnt/frizzled signaling at 5 weeks follow-up. Taken together, IPT limited infarct expansion and altered infarct composition, showing that IPT influences remodeling of the infarct zone, likely by increasing regional myofibroblast content.

  20. [Remodeling of Cardiovascular System: Causes and Consequences]. (United States)

    Lopatina, E V; Kipenko, A V; Penniyaynen, V A; Pasatetckaia, N A; Tsyrline, V A


    Literature and our data suggest the regulatory action of a number of biologically active substances (catecholamines, cardiac glycosides, β-blockers, angiotensin-converting-enzyme inhibitor) on the growth and proliferation of heart cells. By using of organotypic tissue culture has proved that the basis of this regulation is the ability of test substances, receptor- or transducer-mediated signaling to modulate the function of Na⁺, K⁺-ATPase. There is a delay in the development of vascular smooth muscle in the late postnatal period in rats with the blockade of the sympathetic nervous system in the prenatal period. The relationship between vascular remodeling and contractile activity is described. It seems that one of the causes of high blood pressure is a remodeling of the cardiovascular system, which precedes the development of hypertension.

  1. The buzz on fly neuronal remodeling. (United States)

    Hewes, Randall S


    Hormone-dependent rewiring of axons and dendrites is a conserved feature of nervous system development and plasticity. During metamorphosis in insects, steroid hormones (the ecdysteroids) and terpenoid hormones (the juvenile hormones) regulate extensive remodeling of the nervous system. These changes retool the nervous system for new behavioral and physiological functions that are required for the adult stage of the life cycle. In honey bees and other highly social insects, hormones also regulate behavioral changes and neuronal plasticity associated with transitions between social caste roles. This review focuses on recent work in fruit flies and honey bees that reveals hormonal and molecular mechanisms underlying metamorphic and caste-dependent neuronal remodeling, with specific emphasis on the role of Krüppel homolog 1.

  2. Remodeling of Calcium Entry Pathways in Cancer. (United States)

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía


    Ca(2+) entry pathways play important roles in control of many cellular functions, including long-term proliferation, migration and cell death. In recent years, it is becoming increasingly clear that, in some types of tumors, remodeling of Ca(2+) entry pathways could contribute to cancer hallmarks such as excessive proliferation, cell migration and invasion as well as resistance to cell death or survival. In this chapter we briefly review findings related to remodeling of Ca(2+) entry pathways in cancer with emphasis on the mechanisms that contribute to increased store-operated Ca(2+) entry (SOCE) and store-operated currents (SOCs) in colorectal cancer cells. Finally, since SOCE appears critically involved in colon tumorogenesis, the inhibition of SOCE by aspirin and other NSAIDs and its possible contribution to colon cancer chemoprevention is reviewed.

  3. Application of Petri Nets in Bone Remodeling

    Directory of Open Access Journals (Sweden)

    Lingxi Li


    Full Text Available Understanding a mechanism of bone remodeling is a challenging task for both life scientists and model builders, since this highly interactive and nonlinear process can seldom be grasped by simple intuition. A set of ordinary differential equations (ODEs have been built for simulating bone formation as well as bone resorption. Although solving ODEs numerically can provide useful predictions for dynamical behaviors in a continuous time frame, an actual bone remodeling process in living tissues is driven by discrete events of molecular and cellular interactions. Thus, an event-driven tool such as Petri nets (PNs, which may dynamically and graphically mimic individual molecular collisions or cellular interactions, seems to augment the existing ODE-based systems analysis. Here, we applied PNs to expand the ODE-based approach and examined discrete, dynamical behaviors of key regulatory molecules and bone cells. PNs have been used in many engineering areas, but their application to biological systems needs to be explored. Our PN model was based on 8 ODEs that described an osteoprotegerin linked molecular pathway consisting of 4 types of bone cells. The models allowed us to conduct both qualitative and quantitative evaluations and evaluate homeostatic equilibrium states. The results support that application of PN models assists understanding of an event-driven bone remodeling mechanism using PN-specific procedures such as places, transitions, and firings.

  4. Bone Remodelling Markers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Patrice Fardellone


    Full Text Available Bone loss in rheumatoid arthritis (RA patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin, serum aminoterminal propeptide of type I collagen (PINP, serum carboxyterminal propeptide of type I collagen (ICTP, bone alkaline phosphatase (BAP, osteocalcin (OC, and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX, N-terminal telopeptide of type 1 collagen (I-NTX, pyridinolines (DPD and PYD, and tartrate-resistant acid phosphatase (TRAP. Bone resorption can be seen either in periarticular bone (demineralization and erosion or in the total skeleton (osteoporosis. Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

  5. Predawn and high intensity application of supplemental blue light decreases the quantum yield of PSII and enhances the amount of phenolic acids, flavonoids, and pigments in Lactuca sativa. (United States)

    Ouzounis, Theoharis; Razi Parjikolaei, Behnaz; Fretté, Xavier; Rosenqvist, Eva; Ottosen, Carl-Otto


    To evaluate the effect of blue light intensity and timing, two cultivars of lettuce [Lactuca sativa cv. "Batavia" (green) and cv. "Lollo Rossa" (red)] were grown in a greenhouse compartment in late winter under natural light and supplemental high pressure sodium (SON-T) lamps yielding 90 (±10) μmol m(-2) s(-1) for up to 20 h, but never between 17:00 and 21:00. The temperature in the greenhouse compartments was 22/11°C day/night, respectively. The five light-emitting diode (LED) light treatments were Control (no blue addition), 1B 06-08 (Blue light at 45 μmol m(-2) s(-1) from 06:00 to 08:00), 1B 21-08 (Blue light at 45 μmol m(-2) s(-1) from 21:00 to 08:00), 2B 17-19 (Blue at 80 μmol m(-2) s(-1) from 17:00 to 19:00), and 1B 17-19 (Blue at 45 μmol m(-2) s(-1) from 17:00 to 19:00). Total fresh and dry weight was not affected with additional blue light; however, plants treated with additional blue light were more compact. The stomatal conductance in the green lettuce cultivar was higher for all treatments with blue light compared to the Control. Photosynthetic yields measured with chlorophyll fluorescence showed different response between the cultivars; in red lettuce, the quantum yield of PSII decreased and the yield of non-photochemical quenching increased with increasing blue light, whereas in green lettuce no difference was observed. Quantification of secondary metabolites showed that all four treatments with additional blue light had higher amount of pigments, phenolic acids, and flavonoids compared to the Control. The effect was more prominent in red lettuce, highlighting that the results vary among treatments and compounds. Our results indicate that not only high light level triggers photoprotective heat dissipation in the plant, but also the specific spectral composition of the light itself at low intensities. However, these plant responses to light are cultivar dependent.

  6. Predawn and high intensity application of supplemental blue light decreases the quantum yield of PSII and enhances the amount of phenolic acids, flavonoids, and pigments in Lactuca sativa.

    Directory of Open Access Journals (Sweden)

    Theoharis eOuzounis


    Full Text Available To evaluate the effect of blue light intensity and timing, two cultivars of lettuce [Lactuca sativa cv. ’Batavia’ (green and cv. ‘Lollo Rossa’ (red] were grown in a greenhouse compartment in late winter under natural light and supplemental high pressure sodium (SON-T lamps yielding 90 (±10 µmol m-2 s-1 for up to 20 hr, but never between 17:00 and 21:00. The temperature in the greenhouse compartments was 22/11°C day/night, respectively. The five light-emitting diode (LED light treatments were Control (no blue addition, 1B 06-08 (Blue light at 45 µmol m-2 s-1 from 06:00 to 08:00, 1B 21-08 (Blue light at 45 µmol m-2 s-1 from 21:00 to 08:00, 2B 17-19 (Blue at 80 µmol m-2 s-1 from 17:00 to 19:00, and (1B 17-19 Blue at 45 µmol m-2 s-1from 17:00 to 19:00. Total fresh and dry weight was not affected with additional blue light; however, plants treated with additional blue light were more compact. The stomatal conductance in the green lettuce cultivar was higher for all treatments with blue light compared to the Control. Photosynthetic yields measured with chlorophyll fluorescence showed different response between the cultivars; in red lettuce, the quantum yield of PSII decreased and the yield of non-photochemical quenching increased with increasing blue light, whereas in green lettuce no difference was observed. Quantification of secondary metabolites showed that all four treatments with additional blue light had higher amount of pigments, phenolic acids, and flavonoids compared to the Control. The effect was more prominent in red lettuce, highlighting that the results vary among treatments and compounds. Our results indicate that not only high light level triggers photoprotective heat dissipation in the plant, but also the specific spectral composition of the light itself at low intensities. However, these plant responses to light are cultivar dependent.

  7. Predawn and high intensity application of supplemental blue light decreases the quantum yield of PSII and enhances the amount of phenolic acids, flavonoids, and pigments in Lactuca sativa (United States)

    Ouzounis, Theoharis; Razi Parjikolaei, Behnaz; Fretté, Xavier; Rosenqvist, Eva; Ottosen, Carl-Otto


    To evaluate the effect of blue light intensity and timing, two cultivars of lettuce [Lactuca sativa cv. “Batavia” (green) and cv. “Lollo Rossa” (red)] were grown in a greenhouse compartment in late winter under natural light and supplemental high pressure sodium (SON-T) lamps yielding 90 (±10) μmol m−2 s−1 for up to 20 h, but never between 17:00 and 21:00. The temperature in the greenhouse compartments was 22/11°C day/night, respectively. The five light-emitting diode (LED) light treatments were Control (no blue addition), 1B 06-08 (Blue light at 45 μmol m−2 s−1 from 06:00 to 08:00), 1B 21-08 (Blue light at 45 μmol m−2 s−1 from 21:00 to 08:00), 2B 17-19 (Blue at 80 μmol m−2 s−1 from 17:00 to 19:00), and 1B 17-19 (Blue at 45 μmol m−2 s−1 from 17:00 to 19:00). Total fresh and dry weight was not affected with additional blue light; however, plants treated with additional blue light were more compact. The stomatal conductance in the green lettuce cultivar was higher for all treatments with blue light compared to the Control. Photosynthetic yields measured with chlorophyll fluorescence showed different response between the cultivars; in red lettuce, the quantum yield of PSII decreased and the yield of non-photochemical quenching increased with increasing blue light, whereas in green lettuce no difference was observed. Quantification of secondary metabolites showed that all four treatments with additional blue light had higher amount of pigments, phenolic acids, and flavonoids compared to the Control. The effect was more prominent in red lettuce, highlighting that the results vary among treatments and compounds. Our results indicate that not only high light level triggers photoprotective heat dissipation in the plant, but also the specific spectral composition of the light itself at low intensities. However, these plant responses to light are cultivar dependent. PMID:25767473

  8. Role of arginase in vessel wall remodeling

    Directory of Open Access Journals (Sweden)

    William eDurante


    Full Text Available Arginase metabolizes the semi-essential amino acid L-arginine to L-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and L-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages towards an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide synthesis by competing with nitric oxide synthase for substrate, L-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease.

  9. Pregnancy-induced remodeling of heart valves. (United States)

    Pierlot, Caitlin M; Moeller, Andrew D; Lee, J Michael; Wells, Sarah M


    Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves. Copyright © 2015 the American Physiological Society.

  10. The matrix reorganized: extracellular matrix remodeling and integrin signaling. (United States)

    Larsen, Melinda; Artym, Vira V; Green, J Angelo; Yamada, Kenneth M


    Via integrins, cells can sense dimensionality and other physical and biochemical properties of the extracellular matrix (ECM). Cells respond differently to two-dimensional substrates and three-dimensional environments, activating distinct signaling pathways for each. Direct integrin signaling and indirect integrin modulation of growth factor and other intracellular signaling pathways regulate ECM remodeling and control subsequent cell behavior and tissue organization. ECM remodeling is critical for many developmental processes, and remodeled ECM contributes to tumorigenesis. These recent advances in the field provide new insights and raise new questions about the mechanisms of ECM synthesis and proteolytic degradation, as well as the roles of integrins and tension in ECM remodeling.

  11. Pitx2-mediated cardiac outflow tract remodeling. (United States)

    Ma, Hsiao-Yen; Xu, Jun; Eng, Diana; Gross, Michael K; Kioussi, Chrissa


    Heart morphogenesis involves sequential anatomical changes from a linear tube of a single channel peristaltic pump to a four-chamber structure with two channels controlled by one-way valves. The developing heart undergoes continuous remodeling, including septation. Pitx2-null mice are characterized by cardiac septational defects of the atria, ventricles, and outflow tract. Pitx2-null mice also exhibited a short outflow tract, including unseptated conus and deformed endocardial cushions. Cushions were characterized with a jelly-like structure, rather than the distinct membrane-looking leaflets, indicating that endothelial mesenchymal transition was impaired in Pitx2(-/-) embryos. Mesoderm cells from the branchial arches and neural crest cells from the otic region contribute to the development of the endocardial cushions, and both were reduced in number. Members of the Fgf and Bmp families exhibited altered expression levels in the mutants. We suggest that Pitx2 is involved in the cardiac outflow tract septation by promoting and/or maintaining the number and the remodeling process of the mesoderm progenitor cells. Pitx2 influences the expression of transcription factors and signaling molecules involved in the differentiation of the cushion mesenchyme during heart development. Copyright © 2013 Wiley Periodicals, Inc.

  12. Adipose Tissue Remodeling as Homeostatic Inflammation

    Directory of Open Access Journals (Sweden)

    Michiko Itoh


    Full Text Available Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation. Obese adipose tissue is characterized by dynamic changes in cellular composition and function, which may be referred to as “adipose tissue remodeling”. Among stromal cells in the adipose tissue, infiltrated macrophages play an important role in adipose tissue inflammation and systemic insulin resistance. We have demonstrated that a paracrine loop involving saturated fatty acids and tumor necrosis factor-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 complex, thereby activating macrophages. Such a sustained interaction between endogenous ligands derived from parenchymal cells and pathogen sensors expressed in stromal immune cells should lead to chronic inflammatory responses ranging from the basal homeostatic state to diseased tissue remodeling, which may be referred to as “homeostatic inflammation”. We, therefore, postulate that adipose tissue remodeling may represent a prototypic example of homeostatic inflammation. Understanding the molecular mechanism underlying homeostatic inflammation may lead to the identification of novel therapeutic strategies to prevent or treat obesity-related complications.

  13. [Semiology for gluteal remodeling by lipofilling]. (United States)

    Ho Quoc, C; Mojallal, A


    Gluteal augmentation is a consultation request for many patients. The most common surgical techniques performed for gluteal augmentation employ gluteal implants. However, the results can be frustrating. Liposuction is one of the most common surgical procedures in aesthetic surgery. This surgical procedure can provide some complications. Fat grafting is an effective and predictable way to remodel the buttocks. To get better results, it's important to understand gluteal compartments with a descriptive study. The aim of this study is to describe gluteal semiology for buttocks remodeling with fat grafting. We have described gluteal semiology with our review of literature. We have analyzed fat compartments of gluteal region: volume, links between every compartments, connections with major gluteal muscle and with the skin. We have also analyzed shape and volume of the buttocks. We have described 11 aesthetic subunits, the volume and the shape of the buttocks, and the skin laxity. We did an important literature review to understand the most important gluteal zones to improve for patients' satisfaction. Our gluteal semiology description is very useful to understand liposuction/lipoinjection of gluteal areas. Fat grafting may be a reliable technique, simple and safe procedure. Surgery for correction of the buttocks may involve more than projection and volume. However, these must be in a balanced proportion with the rest of the body. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  14. Effects of acute O3 stress on PSII and PSI photochemistry of sensitive and resistant snap bean genotypes (Phaseolus vulgaris L.), probed by prompt chlorophyll "a" fluorescence and 820 nm modulated reflectance. (United States)

    Salvatori, Elisabetta; Fusaro, Lina; Strasser, Reto J; Bussotti, Filippo; Manes, Fausto


    The response of PSII and PSI photochemistry to acute ozone (O3) stress was tested in a "model plant system", namely the O3 sensitive (S156) and O3 resistant (R123) genotype pairs of Phaseolus vulgaris L., during a phenological phase of higher O3 sensitivity (pod formation). The modulation of the photosynthetic activity during O3 stress was analysed by measuring gas exchanges, Prompt Fluorescence (PF, JIP-test) and 820 nm Modulated Reflectance (MR), a novel techniques which specifically detects the changes in the redox state of P700 and plastocyanin. The results showed that, coherently with genotypic-specific O3 sensitivity, the response of the two snap bean genotypes differed for the intensity and time of onset of the considered physiological changes. In fact, despite leaf injury and gas exchanges reduction appeared concurrently in both genotypes, S156 showed a PSII down regulation already after the first day of fumigation (DOF), and an enhancement of Cyclic Electron Flow of PSI after the second DOF, whereas R123 showed only slight adjustments until the third DOF, when the activity of both photosystems was down-regulated. Despite these differences, it is possible to distinguish in both genotypes an early O3 response of the photochemical apparatus, involving PSII only, and a following response, in which PSI activity and content are also modulated. The measurement of the MR signal, performed simultaneously with the PF measurements and the JIP-test analysis, has allowed a better understanding of the role that PSI plays in the O3 stress response of the S156/R123 model plant system. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. Cold-acclimation limits low temperature induced photoinhibition by promoting a higher photochemical quantum yield and a more effective PSII restoration in darkness in the Antarctic rather than the Andean ecotype of Colobanthus quitensis Kunt Bartl (Cariophyllaceae

    Directory of Open Access Journals (Sweden)

    Bascuñán-Godoy Luisa


    Full Text Available Abstract Background Ecotypes of Colobanthus quitensis Kunt Bartl (Cariophyllaceae from Andes Mountains and Maritime Antarctic grow under contrasting photoinhibitory conditions, reaching differential cold tolerance upon cold acclimation. Photoinhibition depends on the extent of photodamage and recovery capability. We propose that cold acclimation increases resistance to low-temperature-induced photoinhibition, limiting photodamage and promoting recovery under cold. Therefore, the Antarctic ecotype (cold hardiest should be less photoinhibited and have better recovery from low-temperature-induced photoinhibition than the Andean ecotype. Both ecotypes were exposed to cold induced photoinhibitory treatment (PhT. Photoinhibition and recovery of photosystem II (PSII was followed by fluorescence, CO2 exchange, and immunoblotting analyses. Results The same reduction (25% in maximum PSII efficiency (Fv/Fm was observed in both cold-acclimated (CA and non-acclimated (NA plants under PhT. A full recovery was observed in CA plants of both ecotypes under dark conditions, but CA Antarctic plants recover faster than the Andean ecotype. Under PhT, CA plants maintain their quantum yield of PSII, while NA plants reduced it strongly (50% and 73% for Andean and Antarctic plants respectively. Cold acclimation induced the maintenance of PsaA and Cyt b6/f and reduced a 41% the excitation pressure in Antarctic plants, exhibiting the lowest level under PhT. xCold acclimation decreased significantly NPQs in both ecotypes, and reduced chlorophylls and D1 degradation in Andean plants under PhT. NA and CA plants were able to fully restore their normal photosynthesis, while CA Antarctic plants reached 50% higher photosynthetic rates after recovery, which was associated to electron fluxes maintenance under photoinhibitory conditions. Conclusions Cold acclimation has a greater importance on the recovery process than on limiting photodamage. Cold acclimation determined the

  16. Reference: 427 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ctions that convert sunlight into chemical energy. Native PSII is a supercomplex co...o et al. 2006 Aug. Proc. Natl. Acad. Sci. U.S.A. 103(33):12631-6. Photosystem II (PSII) catalyzes the first of two photosynthetic rea

  17. Supermolecular organization of photosystem II and its associated light-harvesting antenna in Arabidopsis thaliana

    NARCIS (Netherlands)

    Yakushevska, AE; Jensen, PE; Keegstra, W; van Roon, H; Scheller, HV; Boekema, EJ; Dekker, JP; Yakushevska, Alevtyna E.; Jensen, Poul E.; Scheller, Henrik V.; Dekker, Jan P.


    The organization of Arabidopsis thaliana photosystem II (PSII) and its associated light-harvesting antenna (LHCII) was studied in isolated PSII-LHCII supercomplexes and native membrane-bound crystals by transmission electron microscopy and image analysis. Over 4000 single-particle projections of

  18. Genetic backgrounds determine brown remodeling of white fat in rodents. (United States)

    Ferrannini, Giulia; Namwanje, Maria; Fang, Bin; Damle, Manashree; Li, Dylan; Liu, Qiongming; Lazar, Mitchell A; Qiang, Li


    Genetic background largely contributes to the complexity of metabolic responses and dysfunctions. Induction of brown adipose features in white fat, known as brown remodeling, has been appreciated as a promising strategy to offset the positive energy balance in obesity and further to improve metabolism. Here we address the effects of genetic background on this process. We investigated browning remodeling in a depot-specific manner by comparing the response of C57BL/6J, 129/Sv and FVB/NJ mouse strains to cold. Surprisingly, 129/Sv and FVB/NJ mice showed distinct brown remodeling features despite their similar resistance to metabolic disorders in comparison to the obesity-prone C57BL/6J mice. FVB/NJ mice demonstrated a preference of brown remodeling in inguinal subcutaneous white adipose tissue (iWAT), whereas 129/Sv mice displayed robust brown remodeling in visceral epididymal fat (eWAT). We further compared gene expression in different depots by RNA-sequencing and identified Hoxc10 as a novel "brake" of brown remodeling in iWAT. Rodent genetic background determines the brown remodeling of different white fat depots. This study provides new insights into the role of genetic variation in fat remodeling in susceptibility to metabolic diseases.

  19. The behavior of adaptive bone-remodeling simulation models

    NARCIS (Netherlands)

    H.H. Weinans (Harrie); R. Huiskes (Rik); H.J. Grootenboer


    textabstractThe process of adaptive bone remodeling can be described mathematically and simulated in a computer model, integrated with the finite element method. In the model discussed here, cortical and trabecular bone are described as continuous materials with variable density. The remodeling rule

  20. Interactions between remodelling, architecture and tissue properties in cancellous bone

    NARCIS (Netherlands)

    J.C. van der Linden (Jacqueline)


    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in

  1. Experimental investigation of bone remodelling using composite femurs.

    NARCIS (Netherlands)

    Waide, V.; Cristofolini, L.; Stolk, J.; Verdonschot, N.J.J.; Toni, A.


    OBJECTIVE: To determine the load transfer patterns of femurs in the intact, immediate post-operative and long-term (remodelled) post-operative implanted conditions for Lubinus SPII and Muller-Curved cemented hip prostheses, and to examine to what extent remodelling may influence the long-term

  2. Remodelling Schools--Experiences from within "Change Teams" (United States)

    Hammersley-Fletcher, Linda; Lowe, Michelle


    This article reports early findings from research commissioned by Staffordshire Local Authority that examines workforce remodelling in schools. As Collarbone (2004) states, workforce remodelling is at the heart of the government's change agenda in maintained schools. It is presented as a tool that will enable schools to think both creatively and…

  3. Galectin-3 and post-myocardial infarction cardiac remodeling

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Pascual-Figal, Domingo A.; de Boer, Rudolf A.


    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in

  4. Molecular mechanisms of synaptic remodeling in alcoholism. (United States)

    Kyzar, Evan J; Pandey, Subhash C


    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. Published by Elsevier Ireland Ltd.

  5. [Structural studies of chromatin remodeling factors]. (United States)

    Volokh, O I; Derkacheva, N I; Studitsky, V M; Sokolova, O S


    Changes of chromatin structure require participation of chromatin remodeling factors (CRFs), which are ATP-dependent multisubunit complexes that change the structure of the nucleosome without covalently modifying its components. CRFs act together with other protein factors to regulate the extent of chromatin condensation. Four CRF families are currently distinguished based on their structural and biochemical characteristics: SWI/SNF, ISWI, Mi-2/CHD, and SWR/INO80. X-ray diffraction analysis and electron microscopy are the main methods to obtain structural information about macromolecules. CRFs are difficult to obtain in crystal because of their large sizes and structural heterogeneity, and transmission electron microscopy (TEM) is mostly employed in their structural studies. The review considers all structures obtained for CRFs by TEM and discusses several models of CRF-nucleosome interactions.

  6. The redox state of transglutaminase 2 controls arterial remodeling.

    Directory of Open Access Journals (Sweden)

    Jeroen van den Akker

    Full Text Available While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2, the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub cellular localization, substrates, and its specific mode of action during small artery inward remodeling. We found that inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required the presence of a reducing agent. The effect of TG2 depended on its cross-linking activity, as indicated by the lack of effect of mutant TG2. The cell-permeable reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced translocation of endogenous TG2 and high membrane-bound transglutaminase activity. This coincided with inward remodeling, characterized by a stiffening of the artery. The remodeling could be inhibited by a TG2 inhibitor and by the nitric oxide donor, SNAP. Using a pull-down assay and mass spectrometry, 21 proteins were identified as TG2 cross-linking substrates, including fibronectin, collagen and nidogen. Inward remodeling induced by low blood flow was associated with the upregulation of several anti-oxidant proteins, notably glutathione-S-transferase, and selenoprotein P. In conclusion, these results show that a reduced state induces smooth muscle membrane-bound TG2 activity. Inward remodeling results from the cross-linking of vicinal matrix proteins, causing a stiffening of the arterial wall.

  7. Atrial remodeling and atrial fibrillation: recent advances and translational perspectives. (United States)

    Nattel, Stanley; Harada, Masahide


    Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. AF and its complications are responsible for important population morbidity and mortality. Presently available therapeutic approaches have limited efficacy and nontrivial potential to cause adverse effects. Thus, new mechanistic knowledge is essential for therapeutic innovation. Atrial arrhythmogenic remodeling, defined as any change in atrial structure or function that promotes atrial arrhythmias, is central to AF. Remodeling can be due to underlying cardiac conditions, systemic processes and conditions such as aging, or AF itself. Recent work has underlined the importance of remodeling in AF, provided new insights into basic mechanisms, and identified new biomarker/imaging approaches to follow remodeling processes. The importance of intracellular Ca(2+) handling abnormalities has been highlighted, both for the induction of triggered ectopic activity and for the activation of Ca(2+)-related cell signaling that mediates profibrillatory remodeling. The importance of microRNAs, which are a new class of small noncoding sequences that regulate gene expression, has emerged in both electrical and structural remodeling. Remodeling related to aging, cardiac disease, and AF itself is believed to underlie the progressive nature of the arrhythmia, which contributes to the complexities of long-term management. New tools that are being developed to quantify remodeling processes and monitor their progression include novel biomarkers, imaging modalities to quantify/localize fibrosis, and noninvasive monitoring/mapping to better characterize the burden of AF and identify arrhythmic sources. This report reviews recent advances in the understanding of the basic pathophysiology of atrial remodeling and potential therapeutic implications. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Cellular Interplay between Cardiomyocytes and Nonmyocytes in Cardiac Remodeling

    Directory of Open Access Journals (Sweden)

    Norifumi Takeda


    Full Text Available Cardiac hypertrophy entails complex structural remodeling involving rearrangement of muscle fibers, interstitial fibrosis, accumulation of extracellular matrix, and angiogenesis. Many of the processes underlying cardiac remodeling have features in common with chronic inflammatory processes. During these processes, nonmyocytes, such as endothelial cells, fibroblasts, and immune cells, residing in or infiltrating into the myocardial interstitium play active roles. This paper mainly addresses the functional roles of nonmyocytes during cardiac remodeling. In particular, we focus on the communication between cardiomyocytes and nonmyocytes through direct cell-cell interactions and autocrine/paracrine-mediated pathways.

  9. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene B; Levin Andersen, Thomas; Marcussen, Niels


    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling...... is lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels...

  10. Cardiovascular remodeling and the peripheral serotonergic system. (United States)

    Ayme-Dietrich, Estelle; Aubertin-Kirch, Gaëlle; Maroteaux, Luc; Monassier, Laurent


    Plasma 5-hydroxytryptamine (5-HT; serotonin), released from blood platelets, plays a major role in the human cardiovascular system. Besides the effect of endogenous serotonin, many drugs targeting serotonergic receptors are widely used in the general population (antiobesity agents, antidepressants, antipsychotics, antimigraine agents), and may enhance the cardiovascular risk. Depending on the type of serotonin receptor activated and its location, the use of these compounds triggers acute and chronic effects. The acute cardiovascular response to 5-HT, named the Bezold-Jarish reflex, leads to intense bradycardia associated with atrioventricular block, and involves 5-HT3, 5-HT1B/1D, 5-HT7 and 5-HT2A/2B receptors. The chronic contribution of 5-HT and its receptors (5-HT4 and 5-HT2A/2B) in cardiovascular tissue remodeling, with a particular emphasis on cardiac hypertrophy, fibrosis and valve degeneration, will be explored in this review. Finally, through the analysis of the effects of sarpogrelate, some new aspects of 5-HT2A receptor pharmacology in vasomotor tone regulation and the interaction between endothelial and smooth muscle cells will also be discussed. The aim of this review is to emphasize the cardiac side effects caused by serotonin receptor activation, and to highlight their possible prevention by the development of new drugs targeting this system. Copyright © 2016. Published by Elsevier Masson SAS.


    Directory of Open Access Journals (Sweden)

    V. R. Veber


    Full Text Available Aim. To study morphologic changes in myocardium of Wistar rats caused by single and long term dopamine administration.Methods. In acute study dopamine 10 mkg/kg was administrated to 15 rats by a single intraperitoneal injection. The material was taken in 2, 6, 24 hours and in 1 month after drug administration. In chronic study dopamine 10 mkg/kg was administrated to 15 rats 3 times a day by intraperitoneal injections during 2 weeks. The material was taken just after the drug administration was stopped and in 1 month of animals keeping without stress and drug influences. Control group included 15 rats comparable with experimental animals in age and weight. They were keeped without stress and drug influences. Morphometric parameters of left and right ventricles were evaluated as well as density of cardiomyocytes, collagen, vessels and volume of extracellular space.Results. The enlargement of cardiac fibrosis is found both in acute, and in chronic study. In acute study cardiac fibrosis was located mainly in a right ventricle. In chronic study cardiac fibrosis was located in both ventricles, but also mainly in a right one.Conclusion. Significant morphological «asynchronism» of the left and right ventricles remodeling requires elaboration of methods of myocardium protection and cardiac function control during dopamine administration. 


    Directory of Open Access Journals (Sweden)

    V. R. Veber


    Full Text Available Aim. To study morphologic changes in myocardium of Wistar rats caused by single and long term dopamine administration.Methods. In acute study dopamine 10 mkg/kg was administrated to 15 rats by a single intraperitoneal injection. The material was taken in 2, 6, 24 hours and in 1 month after drug administration. In chronic study dopamine 10 mkg/kg was administrated to 15 rats 3 times a day by intraperitoneal injections during 2 weeks. The material was taken just after the drug administration was stopped and in 1 month of animals keeping without stress and drug influences. Control group included 15 rats comparable with experimental animals in age and weight. They were keeped without stress and drug influences. Morphometric parameters of left and right ventricles were evaluated as well as density of cardiomyocytes, collagen, vessels and volume of extracellular space.Results. The enlargement of cardiac fibrosis is found both in acute, and in chronic study. In acute study cardiac fibrosis was located mainly in a right ventricle. In chronic study cardiac fibrosis was located in both ventricles, but also mainly in a right one.Conclusion. Significant morphological «asynchronism» of the left and right ventricles remodeling requires elaboration of methods of myocardium protection and cardiac function control during dopamine administration. 

  13. Microcurrent stimulation promotes reverse remodelling in cardiomyocytes. (United States)

    Kapeller, Barbara; Mueller, Johannes; Losert, Udo; Podesser, Bruno K; Macfelda, Karin


    It has been shown that electrical stimulation can improve tissue repair in patients. Imbalances in the extracellular matrix composition induce manifestation of heart failure. Here we investigated the application of microcurrent (MC) to modulate the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in cardiomyocytes in vitro and in vivo to reverse remodelling in the heart in spontaneous hypertensive rats (SHR). Cardiomyocytes from young SHR (7 months) and old SHR (14 months) were stimulated in vitro and in vivo with MC. MMP and TIMP expression were analysed by qPCR and immunofluorescence to evaluate the modulation of MC treatment. Modulation of cardiomyocytes with MC enhances proliferation with no morphological changes in vitro. By electrical stimulation dual effects, increase and decrease, on MMP-2, MMP-9, TIMP-3, and TIMP-4 mRNA as well as protein expression were observed, depending on the age of the cardiomyocytes. In our in vivo study, MC down-regulated MMP-2, MMP-9, and TIMP-4 and increased TIMP-3 in young SHR. In old SHR MMP-2, MMP-9, and TIMP-4 were up-regulated, whereas TIMP-3 was unaffected. Our data indicate that treatment of MC can modulate the expression of MMPs and TIMPs in vitro and in vivo in SHR. Based on these results new treatments for heart failure could be developed.

  14. Book Review: Remodeling GT once again

    Directory of Open Access Journals (Sweden)

    Alvita Nathaniel


    Full Text Available Barry Gibson and Jan Hartman (2014: Rediscovering Grounded Theory London: Sage In their book entitled Rediscovering Grounded Theory, Barry Gibson and Jan Hartman (2014 aim to present grounded theory in a new way with the intention of “forward looking preservation” (p. 237. They claim that Rediscovery is an outcome of many conversations in a London pub over the last eight years. The authors tackle both method and methodology as they meticulously describe the context of The Discovery of Grounded Theory (Glaser & Strauss, 1967 and take an authoritative stand on many of the controversies surrounding remodeling of the method in recent years. Rediscovering also includes substantial how-to sections corresponding to chapters in Glaser’s Theoretical Sensitivity (1978. Rediscovery adds explanatory depth in its discussion of the context of grounded theory, but fails to keep many of its promises. Rediscovery is far reaching. Included in the first part are chapters entitled, What Kind of Theory is Grounded Theory, Constructivism in Grounded Theory, Disentangling Concepts and Categories in Grounded Theory, and Coding in Grounded Theory. These chapters describe the context of the method, discuss the controversies, and present Gibson and Hardman’s positions on contentious issues. The second part of the book consists of chapters that aim to help grounded theorists with procedures such as developing theoretical sensitivity, theoretical sampling, coding, memoing, and writing theory. To their credit, the authors continually acknowledge the originators of the method.

  15. Multiscale Bone Remodelling with Spatial P Systems

    Directory of Open Access Journals (Sweden)

    Diletta Cacciagrano


    Full Text Available Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as our shape-based one already resulted to be highly faithful.

  16. Statins, fracture risk, and bone remodeling. (United States)

    Luisetto, G; Camozzi, V


    Statins inhibit HMG-CoA reductase and reduce the intracellular formation of mevalonate. They are chemical compounds able to reduce total cholesterol by 15-40% and LDL cholesterol by 20-60%, and to increase HDL cholesterol by 5-15%. They also reduce triglycerides by 10- 30%. Statins, blocking the mevalonate pathway, inhibit the prenylation of proteins, which is essential to perform their biological function. A great deal of research has documented the positive effect of statins on bone formation and the importance of bone morphogenetic protein-2 (BMP-2) in mediating this effect. Statins are also able to decrease osteoblast apoptosis. The positive effect of statins on bone formation is accompanied by an inhibition of osteoclast activity, which gives statins the ability to uncouple the bone remodeling processes. Patients taking statins have a higher femoral bone density than those who do not. The lipophilic statins seem to be more effective than the hydrophilic statins in protecting bone. In several clinical trials, but not in all, the use of statins had been associated with a reduction in the fracture risk. In conclusion, statins have a positive effect on bone in vitro, but such an efficacy in humans has yet to be clearly demonstrated. Randomized, controlled trials are needed to provide a satisfactory answer on this issue.

  17. Membrane remodelling during vaccinia virus morphogenesis. (United States)

    Chichón, Francisco Javier; Rodríguez, María Josefa; Risco, Cristina; Fraile-Ramos, Alberto; Fernández, José Jesús; Esteban, Mariano; Carrascosa, José L


    VACV (vaccinia virus) is one of the most complex viruses, with a size exceeding 300 nm and more than 100 structural proteins. Its assembly involves sequential interactions and important rearrangements of its structural components. We have used electron tomography of sections of VACV-infected cells to follow, in three dimensions, the remodelling of the membrane components of the virus during envelope maturation. The tomograms obtained suggest that a number of independent 'crescents' interact with each other to enclose the volume of an incomplete ellipsoid in the viral factory area, attaining the overall shape and size characteristic of the first immature form of the virus [IV (immature virus)]. The incorporation of the DNA into these forms leads to particles with a nucleoid [IVN (IV with nucleoid)] that results in local disorganization of the envelope in regions near the condensed DNA. These particles suffer the progressive disappearance of the membrane outer spikes with a change in the shape of the membrane, becoming locally curled. The transformation of the IVN into the mature virus involves an extreme rearrangement of the particle envelope, which becomes fragmented and undulated. During this process, we also observed connections between the outer membranes with internal ones, suggesting that the latter originate from internalization of the IV envelope. The main features observed for VACV membrane maturation during morphogenesis resemble the breakdown and reassembly of cellular endomembranes.

  18. Neurotrophins in chronic allergic airway inflammation and remodeling. (United States)

    Renz, Harald; Kiliç, Ayşe


    Allergic asthma is a chronic inflammatory disease characterized by the production of allergen-specific IgE antibodies, TH2 inflammation, airway hyperresponsiveness and airway remodeling. Airway remodeling represents the disease-limiting stage during disease progression, and the underlying cellular molecular network resulting in airway remodeling are still poorly defined. In addition to the well-established TH2-dependent inflammatory response, several lines of investigation reveal that this regulation in the peripheral central nervous system contributes to disease development, exacerbation and progression. Several members of the neurotrophin family (e.g. nerve growth factor, brain-derived neurotrophic factor) are important transmitters of signals between the immune and the nervous system. Recent data indicate that NGF contributes to the development of airway remodeling in an inflammation and TGF-independent manner. These and other data open the opportunity to therapeutically interfere also on this level of regulation as a novel approach. Copyright © 2012 S. Karger AG, Basel.

  19. Maternal smoking during pregnancy induces airway remodelling in mice offspring

    NARCIS (Netherlands)

    Blacquiere, M. J.; Timens, W.; Melgert, B. N.; Geerlings, M.; Postma, D. S.; Hylkema, M. N.

    Children from smoking mothers have an increased risk of developing asthma for reasons largely unknown. The effects of maternal smoking during pregnancy on remodelling, allergic airway inflammation and hyperresponsiveness in offspring were investigated in an experimental asthma model. Mice were

  20. Aortic remodelling in aortic dissection after frozen elephant trunk†. (United States)

    Dohle, Daniel-Sebastian; Tsagakis, Konstantinos; Janosi, Rolf Alexander; Benedik, Jaroslav; Kühl, Hilmar; Penkova, Liuba; Stebner, Ferdinand; Wendt, Daniel; Jakob, Heinz


    Frozen elephant trunk (FET) can be used for continuous downstream aorta treatment in acute aortic dissection (AAD) and chronic aortic dissection (CAD). The study reports the changes in the lumen volumes along the downstream aorta towards remodelling. In 70 patients (22 CAD, 48 AAD), pre-, postoperative and at least the 1-year follow-up aortic imaging was available. Volume changes of aortic lumen (AL) and true lumen (TL) between examinations along the stent graft aortic segment (A), downstream to coeliac trunk (B) and distally to bifurcation (C) were used for quantification. TL increase >10% with stable AL or AL decrease >10% with stable TL were classified as positive, changes within a 10% threshold as stable, and all other changes as negative remodelling. In AAD, positive or stable remodelling occurred in A (90%), B (65%), C (58%) within 1 year, thereafter in 26 patients (follow-up: 47 ± 21 months) in A (92%), B (65%), C (62%). Negative remodelling in ≥2 segments was found in 5/26 (19%) patients. In CAD, positive or stable remodelling occurred in A (100%), B (86%), C (77%) within 1 year, thereafter in 16 patients (follow-up: 46 ± 20 months) in A (75%), B (44%), C (38%). Negative remodelling in ≥2 segments was found in 7/16 (43%) patients, 5 underwent reintervention, and stabilized thereafter. FET facilitates positive remodelling in AAD and CAD down to stent graft level. Distally, 20% AAD and 40% CAD patients remain at risk for secondary reintervention, and can be identified by negative remodelling in ≥2 segments in the follow-up examinations. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  1. Vascular remodeling of the mouse yolk sac requires hemodynamic force


    Lucitti, Jennifer L.; Jones, Elizabeth; Huang, Chengqun; Chen, Ju; Fraser, Scott E.; Dickinson, Mary E.


    The embryonic heart and vessels are dynamic and form and remodel while functional. Much has been learned about the genetic mechanisms underlying the development of the cardiovascular system, but we are just beginning to understand how changes in heart and vessel structure are influenced by hemodynamic forces such as shear stress. Recent work has shown that vessel remodeling in the mouse yolk sac is secondarily effected when cardiac function is reduced or absent. These findings indicate that p...

  2. Cardiac Remodelling and Fibrosis in Cardiomyopathy: Role of Galectin-3




    This thesis provides a comprehensive investigation on the contribution of heart scarring, known as cardiac fibrosis, to remodelling and impaired function of the heart. It highlights a relationship between the presence of cardiac fibrosis and severity of irregular heartbeats, and demonstrated the complex role of a molecule called ‘galectin-3’ in the pathogenesis of fibrosis and remodelling in cardiomyopathy. The thesis provides new mechanisms for elevation of galectin-3 blood levels that is in...

  3. Genetic backgrounds determine brown remodeling of white fat in rodents


    Ferrannini, Giulia; Namwanje, Maria; Fang, Bin; Damle, Manashree; Li, Dylan; Liu, Qiongming; Lazar, Mitchell A.; Qiang, Li


    Objective: Genetic background largely contributes to the complexity of metabolic responses and dysfunctions. Induction of brown adipose features in white fat, known as brown remodeling, has been appreciated as a promising strategy to offset the positive energy balance in obesity and further to improve metabolism. Here we address the effects of genetic background on this process. Methods: We investigated browning remodeling in a depot-specific manner by comparing the response of C57BL/6J, 1...

  4. Effect of Ovariectomy on Stimulating Intracortical Remodeling in Rats

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    Chun Lei Li


    Full Text Available Objective. Technically primates and dogs represent ideal models to investigate diseases characterized by abnormal intracortical remodeling. High expenses and ethical issues, however, restrict the use of those animals in research. Rodent models have been used as alternatives instead, but their value is limited, if none, because these animals lack intracortical bone remodeling. This study aimed at investigating the effect of ovariectomy onto the stimulation of intracortical remodeling in rat mandibles. Materials and Methods. Sixteen 12-week-old Spraque-Dawly (SD female rats were randomly assigned into two groups, receiving either ovariectomy or sham operation. All the rats were sacrificed 18 weeks postoperatively. The entire mandibles were harvested for microcomputed tomography (micro-CT and histomorphometric assessments. Results. Micro-CT examination showed significantly decreased bone mineral density (0.95 ± 0.01 versus 1.01 ± 0.02 g/cm3, P<0.001 and bone volume (65.78 ± 5.45 versus 87.41 ± 4.12%, P<0.001 in ovariectomy group. Histomorphometric assessment detected a sixfold increased intracortical bone remodeling as well as an increased bone modeling in mandibles of ovariectomized rats. Conclusion. For the first time, to the authors’ knowledge, it was detected that ovariectomy stimulates intracortical remodeling in rat mandibles. This animal model might be of use to study various bone diseases associated with an abnormal intracortical remodeling process.


    Directory of Open Access Journals (Sweden)

    V. V. Kalyuzhin


    Full Text Available The authors of the review have analyzed papers published on the problem of remodeling of the left ventricle (LV, which is in accordance with a consensus paper from an International Forum on Cardiac Remodeling may be defined as genome expression, molecular, cellular and interstitial changes that are manifested clinically as changes in size, shape and function of the LV after cardiac injury. Remodeling of the LV is often seen as a nonspecific process independent of the nature of the underlying disease (cluster of disease. This approach, contrary to the theory of multimodal response of the myocardium (myocytes and interstitium on the molecular-genetic, cellular, tissue, and organ levels, largely depending on the nature and duration of the triggering factor, as well as modern ideas about the types of LV remodeling and dividing the latter into serdechadaptive and non-adaptive forms, was the subject of legitimate criticism. Analyzed scenarios the molecular and cellular events, as well as deals with diagnosis of left ventricular remodeling. Discusses the classification of LV remodeling.

  6. Cardiac remodeling indicators in adolescent athletes

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    Joaquim Castanheira

    Full Text Available Summary Objective: The idea that different sports and physical training type results in different cardiac adaptations has been widely accepted. However, this remodelling process among different sport modalities is still not fully understood. Thus, the current study aims to investigate the heart morphology variation associated with a set of different modalities characterized by distinct models of preparation and different methods and demands of training and completion. Method: The sample comprises 42 basketball players, 73 roller hockey players, 28 judo athletes and 21 swimmers. Anthropometry was assessed by a single and experienced anthropometrist and the same technician performed the echocardiographic exams. Analysis of variance was used to study age, body size and echocardiograph parameters as well as different sport athlete's comparison. Results: Basketball players are taller (F=23.448; p<0.001; ES-r=0.553, heavier (F=6.702; p<0.001; ES-r=0.334 and have a greater body surface area (F=11.896; p<0.001; ES-r=0.427. Basketball and hockey players have larger left auricle diameters compared with judo athletes (F=3.865; p=0.011; ES-r=0.316. Interventricular end-diastolic septal thickness (F=7.287; p<0.001; ES-r=0.347 and left ventricular posterior wall thickness (F=8.038; p<0.001; ES-r=0.362 of the judokas are smaller compared to the mean values of other sports participants. In addition, relative left parietal ventricular wall thickness is lower among swimmers compared with judokas (F=4.127; p=0.008; ES-r=0.268. Conclusion: The major contributors to changes in heart morphology are for the most part associated with sport-specific training and competition and the specific dynamics and adaptive mechanisms imposed by each sport.

  7. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Gulshan B., E-mail: [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States); University of Calgary, Schulich School of Engineering, Department of Mechanical and Manufacturing Engineering, Calgary, Alberta T2N 1N4 (Canada); Robertson, Douglas D., E-mail: [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States)


    Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula’s material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element’s remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than

  8. Subtype-specific neuronal remodeling during Drosophila metamorphosis. (United States)

    Veverytsa, Lyubov; Allan, Douglas W


    During metamorphosis in holometabolous insects, the nervous system undergoes dramatic remodeling as it transitions from its larval to its adult form. Many neurons are generated through post-embryonic neurogenesis to have adult-specific roles, but perhaps more striking is the dramatic remodeling that occurs to transition neurons from functioning in the larval to the adult nervous system. These neurons exhibit a remarkable degree of plasticity during this transition; many subsets undergo programmed cell death, others remodel their axonal and dendritic arbors extensively, whereas others undergo trans-differentiation to alter their terminal differentiation gene expression profiles. Yet other neurons appear to be developmentally frozen in an immature state throughout larval life, to be awakened at metamorphosis by a process we term temporally-tuned differentiation. These multiple forms of remodeling arise from subtype-specific responses to a single metamorphic trigger, ecdysone. Here, we discuss recent progress in Drosophila melanogaster that is shedding light on how subtype-specific programs of neuronal remodeling are generated during metamorphosis.

  9. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

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    Alberto J Lopez


    Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  10. Mast cells promote lung vascular remodelling in pulmonary hypertension. (United States)

    Hoffmann, J; Yin, J; Kukucka, M; Yin, N; Saarikko, I; Sterner-Kock, A; Fujii, H; Leong-Poi, H; Kuppe, H; Schermuly, R T; Kuebler, W M


    Left heart disease (LHD) frequently causes lung vascular remodelling and pulmonary hypertension (PH). Yet pharmacological treatment for PH in LHD is lacking and its pathophysiological basis remains obscure. We aimed to identify candidate mechanisms of PH in LHD and to test their relevance and therapeutic potential. In rats, LHD was induced by supracoronary aortic banding. Whole genome microarray analyses were performed, candidate genes were confirmed by RT-PCR and Western blots and functional relevance was tested in vivo by genetic and pharmacological strategies. In lungs of LHD rats, mast cell activation was the most prominently upregulated gene ontology cluster. Mast cell gene upregulation was confirmed at RNA and protein levels and remodelled vessels showed perivascular mast cell accumulations. In LHD rats treated with the mast cell stabiliser ketotifen, or in mast cell deficient Ws/Ws rats, PH and vascular remodelling were largely attenuated. Both strategies also reduced PH and vascular remodelling in monocrotaline-induced pulmonary arterial hypertension, suggesting that the role of mast cells extends to non-cardiogenic PH. In PH of different aetiologies, mast cells accumulate around pulmonary blood vessels and contribute to vascular remodelling and PH. Mast cells and mast cell-derived mediators may present promising targets for the treatment of PH.

  11. Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context. (United States)

    Ajijola, Olujimi A; Yagishita, Daigo; Patel, Krishan J; Vaseghi, Marmar; Zhou, Wei; Yamakawa, Kentaro; So, Eileen; Lux, Robert L; Mahajan, Aman; Shivkumar, Kalyanam


    Myocardial infarction (MI) induces neural and electrical remodeling at scar border zones. The impact of focal MI on global functional neural remodeling is not well understood. Sympathetic stimulation was performed in swine with anteroapical infarcts (MI; n = 9) and control swine (n = 9). A 56-electrode sock was placed over both ventricles to record electrograms at baseline and during left, right, and bilateral stellate ganglion stimulation. Activation recovery intervals (ARIs) were measured from electrograms. Global and regional ARI shortening, dispersion of repolarization, and activation propagation were assessed before and during sympathetic stimulation. At baseline, mean ARI was shorter in MI hearts than control hearts (365 ± 8 vs. 436 ± 9 ms, P < 0.0001), dispersion of repolarization was greater in MI versus control hearts (734 ± 123 vs. 362 ± 32 ms(2), P = 0.02), and the infarcted region in MI hearts showed longer ARIs than noninfarcted regions (406 ± 14 vs. 365 ± 8 ms, P = 0.027). In control animals, percent ARI shortening was greater on anterior than posterior walls during right stellate ganglion stimulation (P = 0.0001), whereas left stellate ganglion stimulation showed the reverse (P = 0.0003). In infarcted animals, this pattern was completely lost. In 50% of the animals studied, sympathetic stimulation, compared with baseline, significantly altered the direction of activation propagation emanating from the intramyocardial scar during pacing. In conclusion, focal distal anterior MI alters regional and global pattern of sympathetic innervation, resulting in shorter ARIs in infarcted hearts, greater repolarization dispersion, and altered activation propagation. These conditions may underlie the mechanisms by which arrhythmias are initiated when sympathetic tone is enhanced.

  12. TEF30 Interacts with Photosystem II Monomers and Is Involved in the Repair of Photodamaged Photosystem II in Chlamydomonas reinhardtii. (United States)

    Muranaka, Ligia Segatto; Rütgers, Mark; Bujaldon, Sandrine; Heublein, Anja; Geimer, Stefan; Wollman, Francis-André; Schroda, Michael


    The remarkable capability of photosystem II (PSII) to oxidize water comes along with its vulnerability to oxidative damage. Accordingly, organisms harboring PSII have developed strategies to protect PSII from oxidative damage and to repair damaged PSII. Here, we report on the characterization of the THYLAKOID ENRICHED FRACTION30 (TEF30) protein in Chlamydomonas reinhardtii, which is conserved in the green lineage and induced by high light. Fractionation studies revealed that TEF30 is associated with the stromal side of thylakoid membranes. By using blue native/Deriphat-polyacrylamide gel electrophoresis, sucrose density gradients, and isolated PSII particles, we found TEF30 to quantitatively interact with monomeric PSII complexes. Electron microscopy images revealed significantly reduced thylakoid membrane stacking in TEF30-underexpressing cells when compared with control cells. Biophysical and immunological data point to an impaired PSII repair cycle in TEF30-underexpressing cells and a reduced ability to form PSII supercomplexes after high-light exposure. Taken together, our data suggest potential roles for TEF30 in facilitating the incorporation of a new D1 protein and/or the reintegration of CP43 into repaired PSII monomers, protecting repaired PSII monomers from undergoing repeated repair cycles or facilitating the migration of repaired PSII monomers back to stacked regions for supercomplex reassembly. © 2016 American Society of Plant Biologists. All Rights Reserved.

  13. Mechanisms of tissue remodeling in inflammatory bowel disease. (United States)

    Rieder, Florian; Fiocchi, Claudio


    The clinical course of inflammatory bowel disease (IBD) is highly heterogeneous and often unpredictable, with multiple and serious complications that range from stricture formation to bowel obstruction or perforation, fistula formation and the need for surgery. All these problems are manifestations of tissue remodeling, a secondary but universal response to the insults of chronic inflammation. The factors involved in tissue remodeling are several, including the site and duration of inflammation, soluble molecules, the gut microbiota, and the type of mesenchymal cell response. The prototypical and most common type of tissue remodeling in IBD, and Crohn's disease (CD) in particular, is a fibrotic response, and this review will focus on the factors and mechanisms involved in fibrogenesis, and speculate on what is needed for the development of a rational treatment of intestinal fibrosis. © 2013 S. Karger AG, Basel.

  14. Remodeling of legacy systems in health care using UML. (United States)

    Garde, Sebastian; Knaup, Petra; Herold, Ralf


    Research projects in the field of Medical Informatics often involve the development of application systems. Usually they are developed over a longer period of time, so that at a certain point of time a systematically planned reimplementation is necessary. The first step of reimplementation should be a systematic and comprehensive remodeling. When using UML for this task a systematic approach for remodeling activities is missing. Therefore, we developed a method for remodeling of legacy systems (Qumquad) and applied it to DOSPO, a documentation and therapy planning system for pediatric oncology. Qumquad helps to systematically carry out three steps: the modeling of the current actual state of the application system, the systematic identification of weak points and the development of a target concept for reimplementation considering the identified weak points. Results show that this approach is valuable and feasible and could be applied to various application systems in health care.

  15. Neural circuit rewiring: insights from DD synapse remodeling. (United States)

    Kurup, Naina; Jin, Yishi


    Nervous systems exhibit many forms of neuronal plasticity during growth, learning and memory consolidation, as well as in response to injury. Such plasticity can occur across entire nervous systems as with the case of insect metamorphosis, in individual classes of neurons, or even at the level of a single neuron. A striking example of neuronal plasticity in C. elegans is the synaptic rewiring of the GABAergic Dorsal D-type motor neurons during larval development, termed DD remodeling. DD remodeling entails multi-step coordination to concurrently eliminate pre-existing synapses and form new synapses on different neurites, without changing the overall morphology of the neuron. This mini-review focuses on recent advances in understanding the cellular and molecular mechanisms driving DD remodeling.

  16. Passive ventricular remodeling in cardiac disease: Focus on heterogeneity

    Directory of Open Access Journals (Sweden)

    Elise L Kessler


    Full Text Available Passive ventricular remodeling is defined by the process of molecular ventricular adaptation to different forms of cardiac pathophysiology. It includes changes in tissue architecture, such as hypertrophy, fiber disarray, alterations in cell size and fibrosis. Besides that, it also includes molecular remodeling of gap junctions, especially those composed by Connexin43 proteins (Cx43 in the ventricles that affect cell-to-cell propagation of the electrical impulse, and changes in the sodium channels that modify excitability. All those alterations appear mainly in a heterogeneous manner, creating irregular and inhomogeneous electrical and mechanical coupling throughout the heart. This can predispose to reentry arrhythmias and adds to a further deterioration into heart failure. In this review, passive ventricular remodeling is described in Hypertrophic Cardiomyopathy (HCM, Dilated Cardiomyopathy (DCM, Ischemic Cardiomyopathy (ICM, and Arrhythmogenic Cardiomyopathy (ACM, with a main focus on the heterogeneity of those alterations mentioned above.

  17. Nasomaxillary remodeling and facial form in robust Australopithecus: a reassessment. (United States)

    McCollum, Melanie A


    In a previous study of the patterns of facial growth remodeling characteristic of early hominid taxa, Bromage (1989) demonstrated that the nasoalveolar clivus of A. robustus was resorptive throughout ontogeny. Based upon the remodeling information provided by small samples (n=6 each) of chimpanzees and modern humans, he concluded that the clival resorption pattern characteristic of robust Australopithecus differed significantly from that of chimpanzees and was instead somewhat convergent upon that of modern humans, in that it served to emphasize a downward facial growth vector. The present study used the SEM/replica technique to assess nasomaxillary remodeling in larger, more age-varied samples of chimpanzee (n=33) and modern human crania (n=22). Results indicate far more intraspecific variability in nasomaxillary remodeling than suggested by Bromage's earlier study. In particular, results from an expanded sample demonstrate that the nasoalveolar clivus of chimpanzees is frequently resorptive, especially at later stages of ontogeny. However, the pattern of clival remodeling observed in chimpanzees is unlike that typical of robust Australopithecus, in which clival resorption occurs throughout ontogeny and in expansive fields that cover the entire clival surface. Although Bromage (1989) considered the pattern of nasomaxillary remodeling observed in robust Australopithecus to have been a byproduct of an extreme maxillary growth rotation, the failure of A. africanus to display a similar pattern suggests that some other factor(s) may have been involved. Regardless, it is unlikely that clival resorption in robust Australopithecus would have significantly impacted the overall vector of facial growth. Instead, the primary morphogenetic effect of this pattern of clival resorption would have been one of local surface sculpting.

  18. Airway remodeling and its reversibility in equine asthma

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    Jean-Pierre Lavoie


    Full Text Available Despite effective therapies for controlling its clinical manifestations, human asthma remains an incurable disease. It is now recognized that inflammation induced structural changes (remodeling of the airways are responsible for the progressive loss of lung function in asthmatic patients. However, the peripheral airways, where most of the remodeling occurs in severe asthmatic patients, cannot be safely sampled in humans, and therefore, little is known of the effects of current therapies at reversing the established asthmatic remodeling, especially those occurring in the peripheral airways. Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, experiments in which the disease is artificially induced have been shown to have limited translational potential for humans. To the contrary, horses naturally suffer from an asthma-like condition which shares marked similarities with human asthma making this model unique to investigate the kinetics, reversibility, as well as the physiological consequences of tissue remodeling (Bullone and Lavoie 2015. We reported an increased deposition of smooth muscle, collagen and elastic fibers in the peripheral airways of affected horses, which was correlated with the lung function (Herszberg et al., 2006; Setlakwe et al., 2014. The airway subepithelial collagen depositions were almost completely reversed with 6 to 12 months of treatment with either antigen avoidance or inhaled corticosteroids (ICS administration, and there was a modest (30% on average decrease in airway smooth muscle (Leclere et al., 2011. A recent study also found that ICS combined with long-acting ß2-agonists drugs (LABA and ICS monotherapy similarly induced a 30% decrease of the airway smooth muscle mass at 3 months (Buollone, 2017. However, only ICS/LABA and antigen avoidance decreased airway luminal neutrophilia. The findings indicate the enhance therapeutic effect of ICS

  19. [Experimental therapy of cardiac remodeling with quercetin-containing drugs]. (United States)

    Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A


    It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

  20. Arterial Remodeling After Bioresorbable Scaffolds and Metallic Stents. (United States)

    Serruys, Patrick W; Katagiri, Yuki; Sotomi, Yohei; Zeng, Yaping; Chevalier, Bernard; van der Schaaf, René J; Baumbach, Andreas; Smits, Pieter; van Mieghem, Nicolas M; Bartorelli, Antonio; Barragan, Paul; Gershlick, Anthony; Kornowski, Ran; Macaya, Carlos; Ormiston, John; Hill, Jonathan; Lang, Irene M; Egred, Mohaned; Fajadet, Jean; Lesiak, Maciej; Windecker, Stephan; Byrne, Robert A; Räber, Lorenz; van Geuns, Robert-Jan; Mintz, Gary S; Onuma, Yoshinobu


    Although previous observational studies have documented late luminal enlargement and expansive remodeling following implantation of a bioresorbable vascular scaffold (BVS), no comparison with metallic stents has been conducted in a randomized fashion. This study sought to compare vessel remodeling patterns after either Absorb BVS or Xience metallic drug-eluting stent (DES) implantation (Abbott Vascular, Santa Clara, California) and determine the independent predictors of remodeling. In the ABSORB II randomized trial, 383 lesions (n = 359) were investigated by intravenous ultrasound both post-procedure and at 3-year follow-up. According to vessel and lumen area changes over 3 years, we categorized 9 patterns of vessel remodeling that were beyond the reproducibility of lumen and vessel area measurements. The relative change in mean vessel area was significantly greater with the BVS compared to the DES (6.7 ± 12.6% vs. 2.9 ± 11.5%; p = 0.003); the relative change in mean lumen area was significantly different between the 2 arms (1.4 ± 19.1% vs. -1.9 ± 10.5%, respectively; p = 0.031). Multivariate analysis indicated that use of the BVS, female sex, balloon-artery ratio >1.25, expansion index ≥0.8, previous percutaneous coronary intervention, and higher level of low-density lipoprotein cholesterol were independent predictors of expansive remodeling. Furthermore, in the BVS arm, necrotic core pre-procedure was an independent determinant of expansive remodeling. Expansive vessel wall remodeling was more frequent and intense with the BVS than the metallic DES and could be determined by patient baseline characteristics and periprocedural factors. The clinical effect of the observed lumen and vessel remodeling must be investigated in further large clinical studies to optimize the clinical outcome of patients and lesions treated by bioresorbable scaffolds. (ABSORB II Randomized Controlled Trial; NCT01425281). Copyright © 2017 American College of Cardiology

  1. Integrated Mechanisms of CaMKII-dependent ventricular remodeling

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    Michael M Kreusser


    Full Text Available CaMKII has been shown to be activated during different cardiac pathological processes, and CaMKII-dependent mechanisms contribute to pathological cardiac remodeling, cardiac arrhythmias and contractile dysfunction during heart failure. Activation of CaMKII during cardiac stress results in a broad number of biological effects such as, on the one hand, acute effects due to phosphorylation of distinct cellular proteins as ion channels and calcium handling proteins and, on the other hand, integrative mechanisms by changing gene expression. This review focuses on transcriptional and epigenetic effects of CaMKII activation during chronic cardiac remodeling. Multiple mechanisms have been described how CaMKII mediates changes in cardiac gene expression. CaMKII has been shown to directly phosphorylate components of the cardiac gene regulation machinery. CaMKII phosphorylates several transcription factors such as CREB that induces the activation of specific gene programs. CaMKII activates transcriptional regulators also indirectly by phosphorylating histone deacetylases, especially HDAC4, which in turn inhibits transcription factors that drive cardiac hypertrophy, fibrosis and dysfunction. Recent studies demonstrate that CaMKII also phosphorylate directly histones, which may contribute to changes in gene expression. These findings of CaMKII-dependent gene regulation during cardiac remodeling processes suggest novel strategies for CaMKII-dependent transcriptional or epigenetic therapies to control cardiac gene expression and function. Manipulation of CaMKII-dependent signaling pathways in the settings of pathological cardiac growth, remodeling, and heart failure represents an auspicious therapeutic approach.

  2. Regulator of calcineurin 1 mediates pathological vascular wall remodeling (United States)

    Esteban, Vanesa; Méndez-Barbero, Nerea; Jesús Jiménez-Borreguero, Luis; Roqué, Mercè; Novensá, Laura; Belén García-Redondo, Ana; Salaices, Mercedes; Vila, Luis; Arbonés, María L.


    Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved treatments for these pathologies. Angiotensin II (AngII) is a key effector of aortic wall remodeling that contributes to aneurysm formation and restenosis through incompletely defined signaling pathways. We show that AngII induces vascular smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin (CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed >1,500 AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration. Remarkably, Rcan1−/− mice were resistant to AngII-induced aneurysm and restenosis. Our results indicate that aneurysm formation and restenosis share mechanistic elements and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and restenosis progression. PMID:21930771

  3. Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis

    NARCIS (Netherlands)

    Tjin, Gavin; White, Eric S; Faiz, Alen; Sicard, Delphine; Tschumperlin, Daniel J; Mahar, Annabelle; Kable, Eleanor P W; Burgess, Janette K


    Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with feweffective therapeutic options. Structural remodelling of the extracellular matrix [i.e. collagen cross-linkingmediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4)] might contribute to disease

  4. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

    NARCIS (Netherlands)

    Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.

    Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an

  5. The redox state of transglutaminase 2 controls arterial remodeling

    DEFF Research Database (Denmark)

    van den Akker, Jeroen; VanBavel, Ed; van Geel, Remon


    While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates, ...

  6. The WNT receptor Frizzled-8 in pulmonary remodelling and inflammation

    NARCIS (Netherlands)

    Spanjer, Anita Indra Radha


    Lung diseases as chronic obstructive pulmonary disease (COPD), asthma and pulmonary fibrosis are characterised by similar aberrant inflammatory and repair processes, leading to tissue remodelling. Recent studies have indicated an important role for WNT signalling in the development of these lung

  7. Chromatin remodelers in the DNA double strand break response

    NARCIS (Netherlands)

    Smeenk, Godelieve


    During my PhD project, I studied the role of several chromatin remodelers in the DNA double strand break (DSB) response. We discovered that both CHD4 and SMARCA5 are required for ubiquitin signaling through the E3 ubiquitin ligases RNF8 and RNF168, which is a central signaling event in the response

  8. Airway structural components drive airway smooth muscle remodeling in asthma

    NARCIS (Netherlands)

    Dekkers, Bart G J; Maarsingh, Harm; Meurs, Herman; Gosens, Reinoud


    Chronic asthma is an inflammatory airways disease characterized by pathological changes in the airway smooth muscle (ASM) bundle that contribute to airway obstruction and hyperresponsiveness. Remodeling of the ASM is associated with an increased smooth muscle mass, involving components of cellular

  9. Frequent involvement of chromatin remodeler alterations in gastric field cancerization. (United States)

    Takeshima, Hideyuki; Niwa, Tohru; Takahashi, Takamasa; Wakabayashi, Mika; Yamashita, Satoshi; Ando, Takayuki; Inagawa, Yuki; Taniguchi, Hirokazu; Katai, Hitoshi; Sugiyama, Toshiro; Kiyono, Tohru; Ushijima, Toshikazu


    A field for cancerization, or a field defect, is formed by the accumulation of genetic and epigenetic alterations in normal-appearing tissues, and is involved in various cancers, especially multiple cancers. Epigenetic alterations are frequently present in chronic inflammation-exposed tissues, but information on individual genes involved in the formation of a field defect is still fragmental. Here, using non-cancerous gastric tissues of cancer patients, we isolated 16 aberrantly methylated genes, and identified chromatin remodelers ACTL6B and SMARCA1 as novel genes frequently methylated in non-cancerous tissues. SMARCA1 was expressed at high levels in normal gastric tissues, but was frequently silenced by aberrant methylation in gastric cancer cells. Moreover, somatic mutations of additional chromatin remodelers, such as ARID1A, SMARCA2, and SMARCA4, were found in 30% of gastric cancers. Mutant allele frequency suggested that the majority of cancer cells harbored a mutation when present. Depletion of a chromatin remodeler, SMARCA1 or SMARCA2, in cancer cell lines promoted their growth. These results showed that epigenetic and genetic alterations of chromatin remodelers are induced at an early stage of carcinogenesis and are frequently involved in the formation of a field defect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. The redox state of transglutaminase 2 controls arterial remodeling

    NARCIS (Netherlands)

    van den Akker, Jeroen; VanBavel, Ed; van Geel, Remon; Matlung, Hanke L.; Guvenc Tuna, Bilge; Janssen, George M. C.; van Veelen, Peter A.; Boelens, Wilbert C.; de Mey, Jo G. R.; Bakker, Erik N. T. P.


    While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates, and

  11. Lung tissue remodeling in the acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Souza Alba Barros de


    Full Text Available Acute respiratory distress syndrome (ARDS is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibropro­liferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient?s prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

  12. Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Minicucci, Marcos; Oliveira, Fernando; Santos, Priscila; Polegato, Bertha; Roscani, Meliza; Fernandes, Ana Angelica; Lustosa, Beatriz; Paiva, Sergio; Zornoff, Leonardo; Azevedo, Paula, E-mail: [Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, São Paulo, SP (Brazil)


    Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

  13. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension. (United States)

    Ghobadi, G; Bartelds, B; van der Veen, S J; Dickinson, M G; Brandenburg, S; Berger, R M F; Langendijk, J A; Coppes, R P; van Luijk, P


    Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an important role in the development of radiation-induced pulmonary toxicity. Therefore, the authors investigated whether irradiation of the lung also induces pulmonary hypertension. Different sub-volumes of the rat lung were irradiated with protons known to induce different levels of pulmonary vascular damage. Early loss of endothelial cells and vascular oedema were observed in the irradiation field and in shielded parts of the lung, even before the onset of clinical symptoms. 8 weeks after irradiation, irradiated volume-dependent vascular remodelling was observed, correlating perfectly with pulmonary artery pressure, right ventricle hypertrophy and pulmonary dysfunction. The findings indicate that partial lung irradiation induces pulmonary vascular remodelling resulting from acute pulmonary endothelial cell loss and consequential pulmonary hypertension. Moreover, the close resemblance of the observed vascular remodelling with vascular lesions in PAH makes partial lung irradiation a promising new model for studying PAH.

  14. Remodeling of inhibitory synaptic connections in developing ferret visual cortex

    Directory of Open Access Journals (Sweden)

    Dalva Matthew B


    Full Text Available Abstract Background In the visual cortex, as in many other regions of the developing brain, excitatory synaptic connections undergo substantial remodeling during development. While evidence suggests that local inhibitory synapses may behave similarly, the extent and mechanisms that mediate remodeling of inhibitory connections are not well understood. Results Using scanning laser photostimulation in slices of developing ferret visual cortex, we assessed the overall patterns of developing inhibitory and excitatory synaptic connections converging onto individual neurons. Inhibitory synaptic inputs onto pyramidal neurons in cortical layers 2 and 3 were already present as early as postnatal day 20, well before eye opening, and originated from regions close to the recorded neurons. During the ensuing 2 weeks, the numbers of synaptic inputs increased, with the numbers of inhibitory (and excitatory synaptic inputs peaking near the time of eye opening. The pattern of inhibitory inputs refined rapidly prior to the refinement of excitatory inputs. By uncaging the neurotransmtter GABA in brain slices from animals of different ages, we find that this rapid refinement correlated with a loss of excitatory activity by GABA. Conclusion Inhibitory synapses, like excitatory synapses, undergo significant postnatal remodeling. The time course of the remodeling of inhibitory connections correlates with the emergence of orientation tuning in the visual cortex, implicating these rearrangements in the genesis of adult cortical response properties.

  15. "New Professionalism," Workforce Remodeling and the Restructuring of Teachers' Work (United States)

    Stevenson, Howard; Carter, Bob; Passy, Rowena


    Since its election in 1997 the Labour government's policy has sought to promote a "new professionalism" amongst teachers. First mooted at the time when new performance management arrangements were introduced, the discourse of new professionalism has now become closely associated with the "workforce remodeling" agenda in which…

  16. Energy Efficiency Measures to Incorporate into Remodeling Projects

    Energy Technology Data Exchange (ETDEWEB)

    Liaukus, C. [Building America Research Alliance, Kent, WA (United States)


    Energy improvements in a home are often approached as one concerted effort, beginning with a simple walk-through assessment or more in-depth energy audit and followed by the installation of recommended energy measures. While this approach allows for systems thinking to guide the efforts, comprehensive energy improvements of this nature are undertaken by a relatively small number of U.S. households compared to piecemeal remodeling efforts. In this report, the U.S Department of Energy Building America Retrofit Alliance research team examines the improvement of a home’s energy performance in an opportunistic way by examining what can be done to incorporate energy efficiency measures into general remodeling work and home repair projects. This allows for energy efficiency upgrades to occur at the same time as remodeling proejcts. There are challenges to this approach, not the least of which being that the work will take place over time in potentially many separate projects. The opportunity to improve a home’s energy efficiency at one time expands or contracts with the scope of the remodel. As such, guidance on how to do each piece thoughtfully and with consideration for potential future projects, is critical.

  17. Animal experiment of periodontal tissue remodeling in application of ...

    African Journals Online (AJOL)

    The aim of the present study is to observe the remodeling of periodontal tissue in application of miniimplant anchorage for incisor intrusion in dogs. Six adult male beagle dogs were used for the experiment. On the buccal site, a mini-implant was placed at the interalveolar septum between the maxillary second incisor and ...

  18. Electrophysiological Remodeling in Heart Failure Dyssynchrony vs. Resynchronization

    Directory of Open Access Journals (Sweden)

    Takeshi Aiba, MD PhD


    In conclusion, CRT partially restores DHF-induced ion channel remodeling, abnormal Ca homeostasis, blunted β-adrenergic response and regional heterogeneity of APD, thus may suppress ventricular arrhythmias and contribute to the mortality benefit of CRT as well as improve mechanical performance of the heart.

  19. Characterizing matrix remodeling in collagen gels using optical coherence tomography (United States)

    Levitz, David; Hinds, Monica T.; Hanson, Stephen R.; Jacques, Steven L.


    Optical coherence tomography (OCT) has shown promise at non-destructively characterizing engineered tissues such as collagen gels. However, as the collagen gels develop, the OCT images lose contrast of structures as the gels develop, making visual assessment difficult. Our group proposed quantitatively characterizing these gels by fitting the optical properties from the OCT signals. In this paper, we imaged collagen gels seeded with smooth muscle cells (SMCs) over a 5-day period and used the data to measure their optical properties. Our results showed that over time, the reflectivity of the samples increased 10-fold, corresponding to a decrease in anisotropy factor g, without much change in the scattering coefficient μs. Overall, the optical properties appeared to be dominated by scattering from the collagen matrix, not the cells. However, SMCs remodeled the collagen matrix, and this collagen remodeling by the cells is what causes the observed changes in optical properties. Moreover, the data showed that the optical properties were sensitive to the activity of matrix metalloproteinases (MMPs), enzymes that break down local collagen fibrils into smaller fragments. Blocking MMPs in the SMC gels greatly impeded both the remodeling process and change in optical properties at day 5. Treating day 1 acellular gels with MMP-8 for 3 hr managed to partially reproduce the remodeling observed in SMC gels at day 5. Altogether, we conclude that matrix remodeling in general, and MMPs specifically, greatly affect the local optical properties of the sample, and OCT is a unique tool that can assess MMP activity in collagen gels both non-destructively and label free.

  20. Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis (United States)

    White, Eric S.


    ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with few effective therapeutic options. Structural remodelling of the extracellular matrix [i.e. collagen cross-linking mediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4)] might contribute to disease pathogenesis and represent a therapeutic target. This study aimed to further our understanding of the mechanisms by which LO inhibitors might improve lung fibrosis. Lung tissues from IPF and non-IPF subjects were examined for collagen structure (second harmonic generation imaging) and LO gene (microarray analysis) and protein (immunohistochemistry and western blotting) levels. Functional effects (collagen structure and tissue stiffness using atomic force microscopy) of LO inhibitors on collagen remodelling were examined in two models, collagen hydrogels and decellularized human lung matrices. LOXL1/LOXL2 gene expression and protein levels were increased in IPF versus non-IPF. Increased collagen fibril thickness in IPF versus non-IPF lung tissues correlated with increased LOXL1/LOXL2, and decreased LOX, protein expression. β-Aminoproprionitrile (β-APN; pan-LO inhibitor) but not Compound A (LOXL2-specific inhibitor) interfered with transforming growth factor-β-induced collagen remodelling in both models. The β-APN treatment group was tested further, and β-APN was found to interfere with stiffening in the decellularized matrix model. LOXL1 activity might drive collagen remodelling in IPF lungs. The interrelationship between collagen structural remodelling and LOs is disrupted in IPF lungs. Inhibition of LO activity alleviates fibrosis by limiting fibrillar collagen cross-linking, thereby potentially impeding the formation of a pathological microenvironment in IPF. PMID:29125826

  1. Physiological remodelling of the maternal uterine circulation during pregnancy. (United States)

    Mandala, Maurizio; Osol, George


    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodelling of the entire maternal uterine vasculature. The main focus of this MiniReview is to provide information on upstream (pre-placental) maternal uterine vascular remodelling that facilitates gestational increases in uterine blood flow. Consideration of the three-dimensional pattern of remodelling (circumferential enlargement versus axial elongation), changes in vessel biomechanical properties, and underlying mechanisms [shear stress, nitric oxide, vascular endothelial growth factor (VEGF)/placental growth factor (PlGF), the renin-angiotensin system] and pathways (local versus systemic; venoarterial exchange) are provided using the rat as the principal animal model, although findings from other species are incorporated wherever possible to provide a comparative perspective. The process of maternal gestational uterine vascular remodelling involves a number of cellular processes and mechanisms, including trophoblast invasion, hyperplasia and hypertrophy, and changes in extracellular matrix composition. In addition, changes in cellular function, e.g. the secretory and contractile properties of smooth muscle and an up-regulation of endothelial vasodilatory influences may contribute to uteroplacental blood flow increases through changes in tone as well as in structure. Future studies aimed at better understanding the inter-relationship between changes in vessel structure (remodelling) and function (reactivity) would likely generate new mechanistic insights into the fascinating process of maternal gestational uterine vascular adaptation and provide a more physiological perspective of the underlying cellular processes involved in its regulation. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  2. Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis. (United States)

    Tjin, Gavin; White, Eric S; Faiz, Alen; Sicard, Delphine; Tschumperlin, Daniel J; Mahar, Annabelle; Kable, Eleanor P W; Burgess, Janette K


    Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with few effective therapeutic options. Structural remodelling of the extracellular matrix [i.e. collagen cross-linking mediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4)] might contribute to disease pathogenesis and represent a therapeutic target. This study aimed to further our understanding of the mechanisms by which LO inhibitors might improve lung fibrosis. Lung tissues from IPF and non-IPF subjects were examined for collagen structure (second harmonic generation imaging) and LO gene (microarray analysis) and protein (immunohistochemistry and western blotting) levels. Functional effects (collagen structure and tissue stiffness using atomic force microscopy) of LO inhibitors on collagen remodelling were examined in two models, collagen hydrogels and decellularized human lung matrices. LOXL1/LOXL2 gene expression and protein levels were increased in IPF versus non-IPF. Increased collagen fibril thickness in IPF versus non-IPF lung tissues correlated with increased LOXL1/LOXL2, and decreased LOX, protein expression. β-Aminoproprionitrile (β-APN; pan-LO inhibitor) but not Compound A (LOXL2-specific inhibitor) interfered with transforming growth factor-β-induced collagen remodelling in both models. The β-APN treatment group was tested further, and β-APN was found to interfere with stiffening in the decellularized matrix model. LOXL1 activity might drive collagen remodelling in IPF lungs. The interrelationship between collagen structural remodelling and LOs is disrupted in IPF lungs. Inhibition of LO activity alleviates fibrosis by limiting fibrillar collagen cross-linking, thereby potentially impeding the formation of a pathological microenvironment in IPF. © 2017. Published by The Company of Biologists Ltd.

  3. The transcriptional coactivator SAYP is a trithorax group signature subunit of the PBAP chromatin remodeling complex

    NARCIS (Netherlands)

    G.E. Chalkley (Gillian); Y.M. Moshkin (Yuri); K. Langenberg (Karin); K. Bezstarosti (Karel); A. Blastyak (Andras); H. Gyurkovics (Henrik); J.A.A. Demmers (Jeroen); C.P. Verrijzer (Peter)


    textabstractSWI/SNF ATP-dependent chromatin remodeling complexes (remodelers) perform critical functions in eukaryotic gene expression control. BAP and PBAP are the fly representatives of the two evolutionarily conserved major subclasses of SWI/SNF remodelers. Both complexes share seven core

  4. Natural reversal of pulmonary vascular remodeling and right ventricular remodeling in SU5416/hypoxia-treated Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Makhosazane Zungu-Edmondson

    Full Text Available Pulmonary arterial hypertension (PAH is a lethal disease and improved therapeutic strategies are needed. Increased pulmonary arterial pressure, due to vasoconstriction and vascular remodeling, causes right ventricle (RV failure and death in patients. The treatment of Sprague-Dawley rats with SU5416 injection and exposure to chronic hypoxia for three weeks followed by maintenance in normoxia promote progressive and severe PAH with pathologic features that resemble human PAH. At 5-17 weeks after the SU5416 injection, PAH is developed with pulmonary vascular remodeling as well as RV hypertrophy and fibrosis. The present study investigated subsequent events that occur in these PAH animals.At 35 weeks after the SU5416 injection, rats still maintained high RV pressure, but pulmonary vascular remodeling was significantly reduced. Metabolomics analysis revealed that lungs of normal rats and rats from the 35-week time point had different metabolomics profiles. Despite the maintenance of high RV pressure, fibrosis was resolved at 35-weeks. Masson's trichrome stain and Western blotting monitoring collagen 1 determined 12% fibrosis in the RV at 17-weeks, and this was decreased to 5% at 35-weeks. The level of myofibroblasts was elevated at 17-weeks and normalized at 35-weeks.These results suggest that biological systems possess natural ways to resolve pulmonary and RV remodeling. The resolution of RV fibrosis appears to involve the reduction of myofibroblast-dependent collagen synthesis. Understanding these endogenous mechanisms should help improve therapeutic strategies to treat PAH and RV failure.

  5. Mutation of Neuron-Specific Chromatin Remodeling Subunit BAF53b: Rescue of Plasticity and Memory by Manipulating Actin Remodeling (United States)

    Ciernia, Annie Vogel; Kramár, Enikö A.; Matheos, Dina P.; Havekes, Robbert; Hemstedt, Thekla J.; Magnan, Christophe N.; Sakata, Keith; Tran, Ashley; Azzawi, Soraya; Lopez, Alberto; Dang, Richard; Wang, Weisheng; Trieu, Brian; Tong, Joyce; Barrett, Ruth M.; Post, Rebecca J.; Baldi, Pierre; Abel, Ted; Lynch, Gary; Wood, Marcelo A.


    Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic…

  6. Age-Related Changes in Bone Remodelling and Structure in Men: Histomorphometric Studies

    Directory of Open Access Journals (Sweden)

    Juliet Compston


    Full Text Available Histomorphometric studies of the age-related changes in bone remodelling and structure in men are relatively sparse and mainly limited to the iliac crest. The available data indicate that loss of trabecular bone is predominantly due to decreased formation at the level of individual bone remodelling units and that an increase in remodelling rate does not play a major role. The main structural consequence of the changes in bone remodelling is trabecular thinning. In cortical bone, an age-related reduction in cortical width and increase in porosity have been demonstrated at several skeletal sites. However, the alterations in bone remodelling responsible for these changes remain to be established.

  7. Left ventricular remodeling and torsion dynamics in hypertensive patients. (United States)

    Cameli, Matteo; Lisi, Matteo; Righini, Francesca Maria; Massoni, Alberto; Mondillo, Sergio


    Left ventricular (LV) torsion is a fundamental component of wall motion and plays an important role to optimize ventricular ejection fraction. The aim of our study was to calculate by speckle tracking echocardiography LV twist angle in patients with hypertension and LV remodeling, analyzing torsional indices in all patterns of hypertrophy, in comparison to torsional dynamics of age-matched healthy subjects. Hypertensive patients (n = 202) were divided in three groups, patients with concentric remodeling (n = 70), concentric hypertrophy (n = 68) and eccentric hypertrophy (n = 64), in relation to the echocardiographic measurements of relative wall thickness and LV mass, analyzing their torsional patterns by speckle tracking in comparison to age-matched control group. Compared to healthy controls, LV twist angle was increased in patients with hypertension and concentric remodeling (15.2° ± 1.9° vs. 11.0° ± 1.6°; p < 0.001), reaching the highest value in patients with concentric hypertrophy (19.4° ± 2.6°); instead LV twist angle presented depressed in the group of patients that presented eccentric hypertrophy (5.0° ± 1.1°). Regarding LV untwisting rate, it was higher in the concentric remodeling and concentric hypertrophy groups (-123.1°/s ± 12.1°/s and -145.1°/s ± 15.5°/s, respectively) in comparison with the controls (-90.0°/s ± 10.1°/s; p < 0.0001 for both). Instead, lower values of LV untwisting rate were observed in the eccentric remodeling group (-81.6°/s ± 8.1°/s), not significantly different to controls' values (p = 0.09). Enhanced LV twist angle appears to be a compensatory mechanism in hypertensive patients during the earlier stages of concentric remodeling and concentric hypertrophy; this hyper-torsion is inevitably loss in the more advanced stage of eccentric hypertrophy.

  8. Remodeling myelination: implications for mechanisms of neural plasticity. (United States)

    Chang, Kae-Jiun; Redmond, Stephanie A; Chan, Jonah R


    One of the most significant paradigm shifts in membrane remodeling is the emerging view that membrane transformation is not exclusively controlled by cytoskeletal rearrangement, but also by biophysical constraints, adhesive forces, membrane curvature and compaction. One of the most exquisite examples of membrane remodeling is myelination. The advent of myelin was instrumental in advancing the nervous system during vertebrate evolution. With more rapid and efficient communication between neurons, faster and more complex computations could be performed in a given time and space. Our knowledge of how myelin-forming oligodendrocytes select and wrap axons has been limited by insufficient spatial and temporal resolution. By virtue of recent technological advances, progress has clarified longstanding controversies in the field. Here we review insights into myelination, from target selection to axon wrapping and membrane compaction, and discuss how understanding these processes has unexpectedly opened new avenues of insight into myelination-centered mechanisms of neural plasticity.

  9. Role of Cannabinoids in the Regulation of Bone Remodelling

    Directory of Open Access Journals (Sweden)

    Aymen I Idris


    Full Text Available The endocannabinoid system plays a key role in regulating a variety of physiological processes such as appetite control and energy balance, pain perception, and immune responses. Recent studies have implicated the endocannabinoid system in the regulation of bone cell activity and bone remodelling. These studies showed that endogenous cannabinoid ligands, cannabinoid receptors and the enzymes responsible for ligand synthesis and breakdown all play important roles in bone mass and in the regulation of bone disease. These findings suggest that the endocannabinoid pathway could be of value as a therapeutic target for the prevention and treatment of bone diseases. Here, we review the role of the skeletal endocannabinoid system in the regulation of bone remodelling in health and disease.

  10. p53 regulates cytoskeleton remodeling to suppress tumor progression. (United States)

    Araki, Keigo; Ebata, Takahiro; Guo, Alvin Kunyao; Tobiume, Kei; Wolf, Steven John; Kawauchi, Keiko


    Cancer cells possess unique characteristics such as invasiveness, the ability to undergo epithelial-mesenchymal transition, and an inherent stemness. Cell morphology is altered during these processes and this is highly dependent on actin cytoskeleton remodeling. Regulation of the actin cytoskeleton is, therefore, important for determination of cell fate. Mutations within the TP53 (tumor suppressor p53) gene leading to loss or gain of function (GOF) of the protein are often observed in aggressive cancer cells. Here, we highlight the roles of p53 and its GOF mutants in cancer cell invasion from the perspective of the actin cytoskeleton; in particular its reorganization and regulation by cell adhesion molecules such as integrins and cadherins. We emphasize the multiple functions of p53 in the regulation of actin cytoskeleton remodeling in response to the extracellular microenvironment, and oncogene activation. Such an approach provides a new perspective in the consideration of novel targets for anti-cancer therapy.

  11. Nucleosome breathing and remodeling constrain CRISPR-Cas9 function. (United States)

    Isaac, R Stefan; Jiang, Fuguo; Doudna, Jennifer A; Lim, Wendell A; Narlikar, Geeta J; Almeida, Ricardo


    The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo.

  12. The reversal phase of the bone-remodeling cycle

    DEFF Research Database (Denmark)

    Delaisse, Jean-Marie


    The reversal phase couples bone resorption to bone formation by generating an osteogenic environment at remodeling sites. The coupling mechanism remains poorly understood, despite the identification of a number of 'coupling' osteogenic molecules. A possible reason is the poor attention for the ce......The reversal phase couples bone resorption to bone formation by generating an osteogenic environment at remodeling sites. The coupling mechanism remains poorly understood, despite the identification of a number of 'coupling' osteogenic molecules. A possible reason is the poor attention...... for the cells leading to osteogenesis during the reversal phase. This review aims at creating awareness of these cells and their activities in adult cancellous bone. It relates cell events (i) on the bone surface, (ii) in the mesenchymal envelope surrounding the bone marrow and appearing as a canopy above...

  13. Intradialytic Hypotension and Cardiac Remodeling: A Vicious Cycle

    Directory of Open Access Journals (Sweden)

    Chia-Ter Chao


    Full Text Available Hemodynamic instability during hemodialysis is a common but often underestimated issue in the nephrologist practice. Intradialytic hypotension, namely, a decrease of systolic or mean blood pressure to a certain level, prohibits the safe and smooth achievement of ultrafiltration and solute removal goal in chronic dialysis patients. Studies have elucidated the potential mechanisms involved in the development of Intradialytic hypotension, including excessive ultrafiltration and loss of compensatory mechanisms for blood pressure maintenance. Cardiac remodeling could also be one important piece of the puzzle. In this review, we intend to discuss the role of cardiac remodeling, including left ventricular hypertrophy, in the development of Intradialytic hypotension. In addition, we will also provide evidence that a bidirectional relationship might exist between Intradialytic hypotension and left ventricular hypertrophy in chronic dialysis patients. A more complete understanding of the complex interactions in between could assist the readers in formulating potential solutions for the reduction of both phenomena.

  14. Dynamics of Lung Defense in Pneumonia: Resistance, Resilience, and Remodeling (United States)

    Quinton, Lee J.; Mizgerd, Joseph P.


    Pneumonia is initiated by microbes in the lung, but physiological processes integrating responses across diverse cell types and organ systems dictate the outcome of respiratory infection. Resistance, or actions of the host to eradicate living microbes, in the lungs involves a combination of innate and adaptive immune responses triggered by air-space infection. Resilience, or the ability of the host tissues to withstand the physiologically damaging effects of microbial and immune activities, is equally complex, precisely regulated, and determinative. Both immune resistance and tissue resilience are dynamic and change throughout the lifetime, but we are only beginning to understand such remodeling and how it contributes to the incidence of severe pneumonias, which diminishes as childhood progresses and then increases again among the elderly. Here, we review the concepts of resistance, resilience, and remodeling as they apply to pneumonia, highlighting recent advances and current significant knowledge gaps. PMID:25148693

  15. The extracellular matrix in myocardial injury, repair, and remodeling. (United States)

    Frangogiannis, Nikolaos G


    The cardiac extracellular matrix (ECM) not only provides mechanical support, but also transduces essential molecular signals in health and disease. Following myocardial infarction, dynamic ECM changes drive inflammation and repair. Early generation of bioactive matrix fragments activates proinflammatory signaling. The formation of a highly plastic provisional matrix facilitates leukocyte infiltration and activates infarct myofibroblasts. Deposition of matricellular proteins modulates growth factor signaling and contributes to the spatial and temporal regulation of the reparative response. Mechanical stress due to pressure and volume overload and metabolic dysfunction also induce profound changes in ECM composition that contribute to the pathogenesis of heart failure. This manuscript reviews the role of the ECM in cardiac repair and remodeling and discusses matrix-based therapies that may attenuate remodeling while promoting repair and regeneration.

  16. Perspectives on biomechanical growth and remodeling mechanisms in glaucoma(). (United States)

    Grytz, Rafael; Girkin, Christopher A; Libertiaux, Vincent; Downs, J Crawford


    Glaucoma is a blinding diseases in which damage to the axons results in loss of retinal ganglion cells. Experimental evidence indicates that chronic intraocular pressure elevation initiates axonal insult at the level of the lamina cribrosa. The lamina cribrosa is a porous collagen structure through which the axons pass on their path from the retina to the brain. Recent experimental studies revealed the extensive structural changes of the lamina cribrosa and its surrounding tissues during the development and progression of glaucoma. In this perspective paper we review the experimental evidence for growth and remodeling mechanisms in glaucoma including adaptation of tissue anisotropy, tissue thickening/thinning, tissue elongation/shortening and tissue migration. We discuss the existing predictive computational approaches that try to elucidate the potential biomechanical basis of theses growth and remodeling mechanisms and highlight open questions, challenges, and avenues for further development.

  17. Structured near-infrared Magnetic Circular Dichroism spectra of the Mn4CaO5 cluster of PSII in T. vulcanus are dominated by Mn(IV) d-d 'spin-flip' transitions. (United States)

    Morton, Jennifer; Chrysina, Maria; Craig, Vincent S J; Akita, Fusamichi; Nakajima, Yoshiki; Lubitz, Wolfgang; Cox, Nicholas; Shen, Jian-Ren; Krausz, Elmars


    Photosystem II passes through four metastable S-states in catalysing light-driven water oxidation. Variable temperature variable field (VTVH) Magnetic Circular Dichroism (MCD) spectra in PSII of Thermosynochococcus (T.) vulcanus for each S-state are reported. These spectra, along with assignments, provide a new window into the electronic and magnetic structure of Mn4CaO5. VTVH MCD spectra taken in the S2 state provide a clear g=2, S=1/2 paramagnetic characteristic, which is entirely consistent with that known by EPR. The three features, seen as positive (+) at 749nm, negative (-) at 773nm and (+) at 808nm are assigned as 4A→2E spin-flips within the d3 configuration of the Mn(IV) centres present. This assignment is supported by comparison(s) to spin-flips seen in a range of Mn(IV) materials. S3 exhibits a more intense (-) MCD peak at 764nm and has a stronger MCD saturation characteristic. This S3 MCD saturation behaviour can be accurately modelled using parameters taken directly from analyses of EPR spectra. We see no evidence for Mn(III) d-d absorption in the near-IR of any S-state. We suggest that Mn(IV)-based absorption may be responsible for the well-known near-IR induced changes induced in S2 EPR spectra of T. vulcanus and not Mn(III)-based, as has been commonly assumed. Through an analysis of the nephelauxetic effect, the excitation energy of S-state dependent spin-flips seen may help identify coordination characteristics and changes at each Mn(IV). A prospectus as to what more detailed S-state dependent MCD studies promise to achieve is outlined. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Modification of infarct material properties limits adverse ventricular remodeling. (United States)

    Morita, Masato; Eckert, Chad E; Matsuzaki, Kanji; Noma, Mio; Ryan, Liam P; Burdick, Jason A; Jackson, Benjamin M; Gorman, Joseph H; Sacks, Michael S; Gorman, Robert C


    Infarct expansion after myocardial infarction (MI) is an important phenomenon that initiates and sustains adverse left ventricular (LV) remodeling. We tested the hypothesis that infarct modification by material-induced infarct stiffening and thickening limits infarct expansion and LV remodeling. Anteroapical infarction was induced in 21 sheep. Sheep were randomized to injection of saline (2.6 mL) or tissue filler material (2.6 mL) into the infarct within 3 hours of MI. Animals were monitored for 8 weeks with echocardiography to assess infarct expansion and global LV remodeling. Morphometric measurements were performed of excised hearts to quantify infarct thickness. Regional blood flow was assessed with colored microspheres. Infarct material properties were measured using biaxial tensile testing. Compared with controls at 8 weeks, treatment animals had less infarct expansion, reduced LV dilatation (LV systolic volumes: 60.8±4.3 vs 80.3±6.9 mL; p<0.05), greater ejection fraction (0.310±0.026 vs 0.276±0.013; p<0.05), thicker infarcts (5.5±0.2 vs 2.2±0.3 mm; p<0.05), and greater infarct blood flow (0.22±0.04 vs 0.11±0.03 mL/min/g; p<0.05). The longitudinal peak strain in the treatment group was less (0.05014±0.0141) than the control group (0.1024±0.0101), indicating increased stiffness of the treated infarcts. Durable infarct thickening and stiffening can be achieved by infarct biomaterial injection, resulting in the amelioration of infarct expansion and global LV remodeling. Further material optimization will allow for clinical translation of this novel treatment paradigm. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Cell Wall Composition, Biosynthesis and Remodeling during Pollen Tube Growth


    Jean-Claude Mollet; Christelle Leroux; Flavien Dardelle; Arnaud Lehner


    The pollen tube is a fast tip-growing cell carrying the two sperm cells to the ovule allowing the double fertilization process and seed setting. To succeed in this process, the spatial and temporal controls of pollen tube growth within the female organ are critical. It requires a massive cell wall deposition to promote fast pollen tube elongation and a tight control of the cell wall remodeling to modify the mechanical properties. In addition, during its journey, the pollen tube interacts with...



    Langevin, HM; Fujita, T.; Bouffard, NA; Takano, T; Koptiuch, C; Badger, GJ; Nedergaard, M


    Fibroblasts in whole areolar connective tissue respond to static stretching of the tissue by expanding and remodeling their cytoskeleton within minutes both ex vivo and in vivo. This study tested the hypothesis that the mechanism of fibroblast expansion in response to tissue stretch involves extracellular ATP signaling. In response to tissue stretch ex vivo, ATP levels in the bath solution increased significantly, and this increase was sustained for 20 minutes, returning to baseline at 60 min...

  1. Modeling Effects of Axial Extension on Arterial Growth and Remodeling


    Valentín, A.; Humphrey, J. D.


    Diverse mechanical perturbations elicit arterial growth and remodeling responses that appear to optimize structure and function so as to achieve mechanical homeostasis. For example, it is well known that functional adaptations to sustained changes in transmural pressure and blood flow primarily affect wall thickness and caliber to restore circumferential and wall shear stresses toward normal. More recently, however, it has been shown that changes in axial extension similarly prompt dramatic c...

  2. Energy Efficiency Measures to Incorporate into Remodeling Projects

    Energy Technology Data Exchange (ETDEWEB)

    Liaukus, C.


    Energy improvements in a home are often approached as one concerted effort, beginning with a simple walk-through assessment or more in-depth energy audit and followed by the installation of recommended energy measures. While this approach allows for systems thinking to guide the efforts, comprehensive energy improvements of this nature are undertaken by a relatively small number of the households in our nation compared to more piecemeal remodeling efforts. Even when programs like the Weatherization Assistance Program and Home Performance with ENERGY STAR are considered, homes that have had a comprehensive energy makeover still represent a small fraction of the 111.1 million households. In this report, the U.S Department of Energy Building America Retrofit Alliance research team looks at the improvement of a home's energy performance in an opportunistic way: it examines what can be done to incorporate energy efficiency measures into general remodeling work and home repair projects. This allows for the possibility for people who would not normally pursue energy efficiency but will remodel their kitchen or re-side their home to improve their home's performance at the same time. There are challenges to this approach, not the least of which being that the work will take place over time in potentially many separate projects. The opportunity to improve a home's energy efficiency at one time expands or contracts with the scope of the remodel. As such, guidance on how to do each piece thoughtfully and with consideration for potential future projects, is critical.

  3. Remodeling Intestinal Flora with Sleeve Gastrectomy in Diabetic Rats


    Xiaofei Huang; Pan Weng; Huixin Zhang; Yingli Lu


    Objective. As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. Methods. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them und...

  4. Does maxillary arch remodeling exist in nasal polyposis? (United States)

    Gunhan, Kivanc; Can, Fatma; Uz, Uzdan; Serter, Selim; Unlu, Halis


    The potential transformation in the maxillary complex morphology is mostly complete during childhood. Recent studies suggest a nasal tissue remodeling both in the overlying mucosa and in the underlying sinus bone in nasal polyposis (NP). Our evaluation of computed tomography (CT) revealed that the maxillary arch is more flat and shallow in patients with chronic rhinosinusitis with NP. The purpose of this study was to determine the possible effects of NP to the maxillary arch morphology in adulthood and to investigate a possible remodeling of the maxillary bone during the course of NP. A prospective study was performed on 25 patients. Grading of the polyps, acoustic rhinometry and rhinomanometry assessments, and CT scans were documented initially, 1 year after diagnosis, and 2 years postoperatively. Twenty-five subjects' CT scans randomly selected from our CT database formed the comparison group. The plane angle between the maxillary alveolar processes (MAP) and the palatine process of the maxillary bone (MPP), and the depth of the maxillary arch of both groups were compared. The results pointed out that the maxillary arch was shallower and the bilateral angles between MAP and MPP were significantly greater than those of the comparison group in all evaluation periods. This difference was less at the end of the postoperative follow-up period. Although it is a common belief that maxillofacial formation expires in childhood, this may not be the case under some special conditions such as NP in adulthood. NP might cause maxillary arch remodeling in adults.

  5. Molecular mechanism of obesity-induced "metabolic" tissue remodeling. (United States)

    Tanaka, Miyako; Itoh, Michiko; Ogawa, Yoshihiro; Suganami, Takayoshi


    Chronic inflammation is a common molecular basis underlying a variety of chronic diseases. Accumulating evidence has also suggested that chronic inflammation contributes to the pathogenesis of obesity and diabetes, which have been considered as a metabolic disease. For the last several decades, there was a dramatic progress in the underlying mechanism of adipose tissue dysfunction induced by obesity. Tissue remodeling is one of the histological features of chronic inflammation, in which stromal cells dramatically change in number and cell type. Indeed, adipose tissue remodeling is induced by various stromal cells and results in the impairment of adipose tissue function such as adipocytokine production and lipid storage, which leads to systemic metabolic disorder. In addition to adipose tissue, liver is another example of obesity-induced tissue remodeling. In this review, we will discuss how obesity induces interstitial fibrosis in adipose tissue and liver, particularly focusing on the role of macrophages. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Circadian Rhythms and Memory Formation: Regulation by Chromatin Remodeling

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    Saurabh eSahar


    Full Text Available Epigenetic changes, such as DNA methylation or histone modification, can remodel the chromatin and regulate gene expression. Remodeling of chromatin provides an efficient mechanism of transducing signals, such as light or nutrient availability, to regulate gene expression. CLOCK:BMAL1 mediated activation of clock-controlled genes (CCGs is coupled to circadian changes in histone modification at their promoters. Several chromatin modifiers, such as the deacetylases SIRT1 and HDAC3 or methyltransferase MLL1, have been shown to be recruited to the promoters of the CCGs in a circadian manner. Interestingly, the central element of the core clock machinery, the transcription factor CLOCK, also possesses histone acetyltransferase activity. Rhythmic expression of the CCGs is abolished in the absence of these chromatin modifiers. Recent research has demonstrated that chromatin remodeling is at the cross-roads of circadian rhythms and regulation of metabolism and aging. It would be of interest to identify if similar pathways exist in the epigenetic regulation of memory formation.

  7. Thyroid hormone promotes remodeling of coronary resistance vessels.

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    Olga V Savinova

    Full Text Available Low thyroid hormone (TH function has been linked to impaired coronary blood flow, reduced density of small arterioles, and heart failure. Nonetheless, little is known about the mechanisms by which THs regulate coronary microvascular remodeling. The current study examined the initial cellular events associated with coronary remodeling induced by triiodothyronine (T3 in hypothyroid rats. Rats with established hypothyroidism, eight weeks after surgical thyroidectomy (TX, were treated with T3 for 36 or 72 hours. The early effects of T3 treatment on coronary microvasculature were examined morphometrically. Gene expression changes in the heart were assessed by quantitative PCR Array. Hypothyroidism resulted in arteriolar atrophy in the left ventricle. T3 treatment rapidly induced small arteriolar muscularization and, within 72 hours, restored arteriolar density to control levels. Total length of the capillary network was not affected by TX or T3 treatment. T3 treatment resulted in the coordinate regulation of Angiopoietin 1 and 2 expression. The response of Angiopoietins was consistent with vessel enlargement. In addition to the well known effects of THs on vasoreactivity, these results suggest that THs may affect function of small resistance arteries by phenotypic remodeling of vascular smooth muscle cells (VSMC.


    Bieszczad, Kasia M.; Miasnikov, Alexandre A.; Weinberger, Norman M.


    Neural mechanisms underlying the capacity of memory to be rich with sensory detail are largely unknown. A candidate mechanism is learning-induced plasticity that remodels adult sensory cortex. Here, expansion in the primary auditory cortical (A1) tonotopic map of rats was induced by pairing a 3.66 kHz tone with activation of the nucleus basalis, mimicking the effects of natural associative learning. Remodeling of A1 produced de novo specific behavioral memory, but neither memory nor plasticity were consistently at the frequency of the paired tone, which typically decreased in A1 representation. Rather, there was a specific match between individual subjects’ area of expansion and the tone that was strongest in each animal’s memory, as determined by post-training frequency generalization gradients. These findings provide the first demonstration of a match between the artificial induction of specific neural representational plasticity and artificial induction of behavioral memory. As such, together with prior and present findings for detection, correlation and mimicry of plasticity with the acquisition of memory, they satisfy a key criterion for neural substrates of memory. This demonstrates that directly remodeling sensory cortical maps is sufficient for the specificity of memory formation. PMID:23639876

  9. A Computational Model for Simulating Spaceflight Induced Bone Remodeling (United States)

    Pennline, James A.; Mulugeta, Lealem


    An overview of an initial development of a model of bone loss due to skeletal unloading in weight bearing sites is presented. The skeletal site chosen for the initial application of the model is the femoral neck region because hip fractures can be debilitating to the overall performance health of astronauts. The paper begins with the motivation for developing such a model of the time course of change in bone in order to understand the mechanism of bone demineralization experienced by astronauts in microgravity, to quantify the health risk, and to establish countermeasures. Following this, a general description of a mathematical formulation of the process of bone remodeling is discussed. Equations governing the rate of change of mineralized bone volume fraction and active osteoclast and osteoblast are illustrated. Some of the physiology of bone remodeling, the theory of how imbalance in remodeling can cause bone loss, and how the model attempts to capture this is discussed. The results of a preliminary validation analysis that was carried out are presented. The analysis compares a set of simulation results against bone loss data from control subjects who participated in two different bed rest studies. Finally, the paper concludes with outlining the current limitations and caveats of the model, and planned future work to enhance the state of the model.

  10. Fibrous tissues growth and remodeling: Evolutionary micro-mechanical theory (United States)

    Lanir, Yoram


    Living fibrous tissues are composite materials having the unique ability to adapt their size, shape, structure and mechanical properties in response to external loading. This adaptation, termed growth and remodeling (G&R), occurs throughout life and is achieved via cell-induced turnover of tissue constituents where some are degraded and new ones are produced. Realistic mathematical modeling of G&R provides insight into the basic processes, allows for hypotheses testing, and constitutes an essential tool for establishing clinical thresholds of pathological remodeling and for the production of tissue substitutes aimed to achieve target structure and properties. In this study, a general 3D micro-mechanical multi-scale theory of G&R in fibrous tissue was developed which connects between the evolution of the tissue structure and properties, and the underlying mechano-biological turnover events of its constituents. This structural approach circumvents a fundamental obstacle in modeling growth mechanics since the growth motion is not bijective. The model was realized for a flat tissue under two biaxial external loadings using data-based parameter values. The predictions show close similarity to characteristics of remodeled adult tissue including its structure, anisotropic and non-linear mechanical properties, and the onset of in situ pre-strain and pre-stress. The results suggest that these important features of living fibrous tissues evolve as they grow.

  11. Mechanisms of arterial remodeling: lessons from genetic diseases

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    Bernard eVan Varik


    Full Text Available Vascular disease is still the leading cause of morbidity and mortality in the Western world, and the primary cause of myocardial infarction, stroke, and ischemia. The biology of vascular disease is complex and still poorly understood in terms of causes and consequences. Vascular function is determined by structural and functional properties of the arterial vascular wall. Arterial stiffness, that is a pathological alteration of the vascular wall, ultimately results in target-organ damage and increased mortality. Arterial remodeling is accelerated under conditions that adversely affect the balance between arterial function and structure such as hypertension, atherosclerosis, diabetes mellitus, chronic kidney disease, inflammatory disease, lifestyle aspects (smoking, drugs (vitamin K antagonists and genetic abnormalities (e.g. pseudoxanthoma elasticum, Marfan’s disease. The aim of this review is to provide an overview of the complex mechanisms and different factors that underlie arterial remodeling, learning from single gene defect diseases like PXE, and PXE-like, Marfan’s disease and Keutel syndrome in vascular remodeling.

  12. Vascular remodeling of the circle of Willis in moyamoya disease. (United States)

    Mikami, Takeshi; Noshiro, Shouhei; Komatsu, Katsuya; Miyata, Kei; Akiyama, Yukinori; Wanibuchi, Masahiko; Mikuni, Nobuhiro


    A positive (outward) remodelling pattern in patients with typical atherosclerotic disease was recognised using magnetic resonance imaging (MRI). In this report, the outer diameter of the circle of Willis was evaluated in patients with moyamoya disease, and its remodelling pattern was verified. A total of 18 consecutive patients with moyamoya disease were included in this analysis. The diameter of the terminal portion of the internal carotid artery (ICA) (C1), proximal portion of the middle cerebral artery (MCA) (M1) and proximal portion of the anterior cerebral artery (A1) was evaluated using fast imaging employing steady-state acquisition (FIESTA) imaging. The outer diameter was estimated using these images, and compared with the control group, and the correlation with magnetic resonance angiography (MRA) scores was calculated for patients with moyamoya disease. The mean diameter of the moyamoya patient group on FIESTA was significantly lower than that of the control group in the C1, M1 and A1 (P moyamoya disease MRA score (y = (0.53x+2.31; R = 0.72), whereas the C1 diameter on the FIESTA image showed only a weak correlation (y = (0.16x+2.47; R = 0.21). We found that the outer diameter of all the vessels around the C1 was generally reduced in patients with moyamoya disease. Diameter of the MCA especially decreases as the disease progresses, similar to the negative (constrictive) remodelling pattern.

  13. Remodeling of Kalri Baghar (K.B Feeder

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    Full Text Available The shortage of irrigation water supplies and reduced water carrying capacity of Kalri Baghar (K.B feeder require remodeling of the canal (an off-taking canal from right bank of Indus River at Kotri Barrage. The designed normal supply level (NSL capacity of K.B feeder was 257 cumecs (9100 cusecs, but it has now maximum flow rate of 241 cumecs (8500 cusecs due to damaged cross-section and silted normal flow area. In present condition only culturable command area (C.C.A needs 277 cumecs, and the requirement of water supply is additional. The hydraulic parameters are revised up to its potential and remodeled the canal using C++ simulation model based on Lacey?s Method and FlowMaster Model. Using these models present discharge is enhanced 5, 10, and 20%, which revealed changes in hydraulic parameters of the canal. The total length of the canal is 5761 m (18,900 ft in which there is 4% of stone pitching and concrete lining and rest of the channel is passing through sandy loam soil, rocks and coarse sand areas. The regime (stable earthen channel cross-section is remodeled using Lacey?s method. The stone and concrete lined section is redesigned by Manning?s procedure using FlowMaster simulation model. It is required and feasible to modify water carrying capacity of the NSL of the channel by 20% as compared to current conditions.

  14. Retinal redox stress and remodeling in cardiometabolic syndrome and diabetes. (United States)

    Yang, Ying; Hayden, Melvin R; Sowers, Susan; Bagree, Sarika V; Sowers, James R


    Diabetic retinopathy (DR) is a significant cause of global blindness; a major cause of blindness in the United States in people aged between 20-74. There is emerging evidence that retinopathy is initiated and propagated by multiple metabolic toxicities associated with excess production of reactive oxygen species (ROS). The four traditional metabolic pathways involved in the development of DR include: increased polyol pathway flux, advanced glycation end-product formation, activation of protein kinase C isoforms, and hexosamine pathway flux. These pathways individually and synergistically contribute to redox stress with excess ROS resulting in retinal tissue injury resulting in significant microvascular blood retinal barrier remodeling. The toxicity of hyperinsulinemia, hyperglycemia, hypertension, dyslipidemia, increased cytokines and growth factors, in conjunction with redox stress, contribute to the development and progression of DR. Redox stress contributes to the development and progression of abnormalities of endothelial cells and pericytes in DR. This review focuses on the ultrastructural observations of the blood retinal barrier including the relationship between the endothelial cell and pericyte remodeling in young nine week old Zucker obese (fa/fa) rat model of obesity; cardiometabolic syndrome, and the 20 week old alloxan induced diabetic porcine model. Preventing or delaying the blindness associated with these intersecting abnormal metabolic pathways may be approached through strategies targeted to reduction of tissue inflammation and oxidative - redox stress. Understanding these abnormal metabolic pathways and the accompanying redox stress and remodeling may provide both the clinician and researcher a new concept of approaching this complicated disease process.

  15. Retinal Redox Stress and Remodeling in Cardiometabolic Syndrome and Diabetes

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    Ying Yang


    Full Text Available Diabetic retinopathy (DR is a significant cause of global blindness; a major cause of blindness in the United States in people aged between 20–74. There is emerging evidence that retinopathy is initiated and propagated by multiple metabolic toxicities associated with excess production of reactive oxygen species (ROS. The four traditional metabolic pathways involved in the development of DR include: increased polyol pathway flux, advanced glycation end-product formation, activation of protein kinase Cisoforms and hexosamine pathway flux. These pathways individually and synergisticallycontribute to redox stress with excess ROS resulting in retinal tissue injury resulting in significant microvascular blood retinal barrier remodeling. The toxicity of hyperinsulinemia, hyperglycemia, hypertension, dyslipidemia, increased cytokines and growth factors, in conjunction with redox stress, contribute to the development and progression of DR. Redox stress contributes to the development and progression of abnormalities of endothelial cells and pericytes in DR. This review focuses on the ultrastructural observations of the blood retinal barrier including the relationship between the endothelial cell and pericyte remodeling in young nine week old Zucker obese (fa/ fa rat model of obesity; cardiometabolic syndrome, and the 20 week old alloxan induced diabetic porcine model. Preventing or delaying the blindness associated with these intersecting abnormal metabolic pathways may be approached through strategies targeted to reduction of tissue inflammation and oxidative—redox stress. Understanding these abnormal metabolic pathways and the accompanying redox stress and remodeling mayprovide both the clinician and researcher a new concept of approaching this complicated disease process

  16. Inflammatory and Bone Remodeling Responses to the Cytolethal Distending Toxins

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    Georgios N. Belibasakis


    Full Text Available The cytolethal distending toxins (CDTs are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved, such as Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Campylobacter jejuni and Helicobacter hepaticus. One special example is the induction of pathological bone destruction in periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, with the potential involvement of its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases.

  17. Remodeling of the methylation landscape in breast cancer metastasis.

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    Marsha Reyngold

    Full Text Available The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process.

  18. The Chd1 Chromatin Remodeler Shifts Nucleosomal DNA Bidirectionally as a Monomer

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    Qiu, Yupeng; Levendosky, Robert F.; Chakravarthy, Srinivas; Patel, Ashok; Bowman, Gregory D.; Myong, Sua


    Chromatin remodelers catalyze dynamic packaging of the genome by carrying out nucleosome assembly/disassembly, histone exchange, and nucleosome repositioning. Remodeling results in evenly spaced nucleosomes, which requires probing both sides of the nucleosome, yet the way remodelers organize sliding activity to achieve this task is not understood. Here, we show that the monomeric Chd1 remodeler shifts DNA back and forth by dynamically alternating between different segments of the nucleosome. During sliding, Chd1 generates unstable remodeling intermediates that spontaneously relax to a pre-remodeled position. We demonstrate that nucleosome sliding is tightly controlled by two regulatory domains: the DNA-binding domain, which interferes with sliding when its range is limited by a truncated linking segment, and the chromodomains, which play a key role in substrate discrimination. We propose that active interplay of the ATPase motor with the regulatory domains may promote dynamic nucleosome structures uniquely suited for histone exchange and chromatin reorganization during transcription.

  19. Soft skills turned into hard facts: nucleosome remodelling at developmental switches. (United States)

    Chioda, M; Becker, P B


    Nucleosome remodelling factors are regulators of DNA accessibility in chromatin and lubricators of all major functions of eukaryotic genomes. Their action is transient and reversible, yet can be decisive for irreversible cell-fate decisions during development. In addition to the well-known local actions of nucleosome remodelling factors during transcription initiation, more global and fundamental roles for remodelling complexes in shaping the epigenome during development are emerging.

  20. Pattern and degree of left ventricular remodeling following a tailored surgical approach for hypertrophic obstructive cardiomyopathy

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    Ismail El-Hamamsy


    Full Text Available Background The role of a tailored surgical approach for hypertrophic cardiomyopathy (HCM on regional ventricular remodelling remains unknown. The aims of this study were to evaluate the pattern, extent and functional impact of regional ventricular remodelling after a tailored surgical approach. Conclusion Following a tailored surgical relief of outflow obstruction for HCM, there is a marked regional reverse LV remodelling. These changes could have a significant impact on overall ventricular dynamics and function.

  1. Remodeling of the postsynaptic plasma membrane during neural development. (United States)

    Tulodziecka, Karolina; Diaz-Rohrer, Barbara B; Farley, Madeline M; Chan, Robin B; Di Paolo, Gilbert; Levental, Kandice R; Waxham, M Neal; Levental, Ilya


    Neuronal synapses are the fundamental units of neural signal transduction and must maintain exquisite signal fidelity while also accommodating the plasticity that underlies learning and development. To achieve these goals, the molecular composition and spatial organization of synaptic terminals must be tightly regulated; however, little is known about the regulation of lipid composition and organization in synaptic membranes. Here we quantify the comprehensive lipidome of rat synaptic membranes during postnatal development and observe dramatic developmental lipidomic remodeling during the first 60 postnatal days, including progressive accumulation of cholesterol, plasmalogens, and sphingolipids. Further analysis of membranes associated with isolated postsynaptic densities (PSDs) suggests the PSD-associated postsynaptic plasma membrane (PSD-PM) as one specific location of synaptic remodeling. We analyze the biophysical consequences of developmental remodeling in reconstituted synaptic membranes and observe remarkably stable microdomains, with the stability of domains increasing with developmental age. We rationalize the developmental accumulation of microdomain-forming lipids in synapses by proposing a mechanism by which palmitoylation of the immobilized scaffold protein PSD-95 nucleates domains at the postsynaptic plasma membrane. These results reveal developmental changes in lipid composition and palmitoylation that facilitate the formation of postsynaptic membrane microdomains, which may serve key roles in the function of the neuronal synapse. © 2016 Tulodziecka et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (

  2. Hypothyroidism and its rapid correction alter cardiac remodeling.

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    Georges Hajje

    Full Text Available The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10 group and a group treated with 6-propyl-2-thiouracil (PTU (n = 20 to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP, tumor necrosis factor alpha (TNF-α, interleukin 6 (IL6 and pro-fibrotic transforming growth factor beta 1 (TGF-β1, were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP and cardiac troponin T (cTnT were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

  3. Hypothyroidism and its rapid correction alter cardiac remodeling. (United States)

    Hajje, Georges; Saliba, Youakim; Itani, Tarek; Moubarak, Majed; Aftimos, Georges; Farès, Nassim


    The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

  4. Sclerostin Promotes Bone Remodeling in the Process of Tooth Movement.

    Directory of Open Access Journals (Sweden)

    Rui Shu

    Full Text Available Tooth movement is a biological process of bone remodeling induced by mechanical force. Sclerostin secreted by osteocytes is mechanosensory and important in bone remodeling. However, little is known regarding the role of sclerostin in tooth movement. In this study, models of experimental tooth movement were established in rats and mice. Sclerostin expression was investigated with immunohistochemistry staining, and osteoclastic activity was analyzed with tartrate-resistant acid phosphatase (TRAP staining. MLO-Y4 osteocyte-like cells underwent uniaxial compression and tension stress or were cultured in hypoxia conditions. Expression of sclerostin was assessed by RT-qPCR and ELISA. MLO-Y4 cells were cultured with recombinant human sclerostin (rhSCL interference and then co-cultured with RAW264.7 osteoclast precursor cells. Expressions of RANKL and OPG were analyzed by RT-qPCR, and osteoclastic activity was assessed by TRAP staining. During tooth movement, sclerostin was expressed differently in compression and tension sites. In SOST knock-out mice, there were significantly fewer TRAP-positive cells than in WT mice during tooth movement in compression sites. In-vitro studies showed that the expression of sclerostin in MLO-Y4 osteocyte-like cells was not different under a uniaxial compression and tension force, whereas hypoxia conditions significantly increased sclerostin expression in MLO-Y4 cells. rhSCL interference increased the expression of RANKL and the RANKL/OPG ratio in MLO-Y4 cells and the osteoclastic induction ability of MLO-Y4 cells in experimental osteocyte-osteoclast co-culture. These data suggest that sclerostin plays an important role in the bone remodeling of tooth movement.

  5. Myocardial infarction: A critical role of macrophages in cardiac remodeling

    Directory of Open Access Journals (Sweden)

    Tobias eWeinberger


    Full Text Available Ischemic heart disease is a common condition and a leading cause of mortality and morbidity. Macrophages, besides their role in host defense and tissue homeostasis, are critical players in the pathophysiological processes induced by myocardial infarction. In this article we will summarize the current understanding of the role of monocytes and macrophages in myocardial damage and cardiac remodeling in relation to their origin and developmental paths. Furthermore, we describe their potential implications in therapeutic strategies to modulate myocardial healing and regeneration.

  6. Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis (United States)

    Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem


    Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

  7. REMOD: a computational tool for remodeling neuronal dendrites

    Directory of Open Access Journals (Sweden)

    Panagiotis Bozelos


    Full Text Available In recent years, several modeling studies have indicated that dendritic morphology is a key determinant of how individual neurons acquire a unique signal processing profile. The highly branched dendritic structure that originates from the cell body, explores the surrounding 3D space in a fractal-like manner, until it reaches a certain amount of complexity. Its shape undergoes significant alterations not only in various neuropathological conditions, but in physiological, too. Yet, despite the profound effect that these alterations can have on neuronal function, the causal relationship between structure and function remains largely elusive. The lack of a systematic approach for remodeling neuronal cells and their dendritic trees is a key limitation that contributes to this problem. In this context, we developed a computational tool that allows the remodeling of any type of neurons, given a set of exemplar morphologies. The tool is written in Python and provides a simple GUI that guides the user through various options to manipulate selected neuronal morphologies. It provides the ability to load one or more morphology files (.swc or .hoc and choose specific dendrites to operate one of the following actions: shrink, remove, extend or branch (as shown in Figure 1. The user retains complete control over the extent of each alteration and if a chosen action is not possible due to pre-existing structural constraints, appropriate warnings are produced. Importantly, the tool can also be used to extract morphology statistics for one or multiple morphologies, including features such as the total dendritic length, path length to the root, branch order, diameter tapering, etc. Finally, an experimental utility enables the user to remodel entire dendritic trees based on preloaded statistics from a database of cell-type specific neuronal morphologies. To our knowledge, this is the first tool that allows (a the remodeling of existing –as opposed to the de novo

  8. Thermally induced osteocyte damage initiates a remodelling signaling cascade.

    Directory of Open Access Journals (Sweden)

    Eimear B Dolan

    Full Text Available Thermal elevations experienced by bone during orthopaedic procedures, such as cutting and drilling, exothermal reactions from bone cement, and thermal therapies such as tumor ablation, can result in thermal damage leading to death of native bone cells (osteocytes, osteoblasts, osteoclasts and mesenchymal stem cells. Osteocytes are believed to be the orchestrators of bone remodeling, which recruit nearby osteoclast and osteoblasts to control resorption and bone growth in response to mechanical stimuli and physical damage. However, whether heat-induced osteocyte damage can directly elicit bone remodelling has yet to be determined. This study establishes the link between osteocyte thermal damage and the remodeling cascade. We show that osteocytes directly exposed to thermal elevations (47°C for 1 minute become significantly apoptotic and alter the expression of osteogenic genes (Opg and Cox2. The Rankl/Opg ratio is consistently down-regulated, at days 1, 3 and 7 in MLO-Y4s heat-treated to 47°C for 1 minute. Additionally, the pro-osteoblastogenic signaling marker Cox2 is significantly up-regulated in heat-treated MLO-Y4s by day 7. Furthermore, secreted factors from heat-treated MLO-Y4s administered to MSCs using a novel co-culture system are shown to activate pre-osteoblastic MSCs to increase production of the pro-osteoblastic differentiation marker, alkaline phosphatase (day 7, 14, and calcium deposition (day 21. Most interestingly, an initial pro-osteoclastogenic signaling response (increase Rankl and Rankl/Opg ratio at day 1 followed by later stage pro-osteoblastogenic signaling (down-regulation in Rankl and the Rankl/Opg ratio and an up-regulation in Opg and Cox2 by day 7 was observed in non-heat-treated MLO-Y4s in co-culture when these were exposed to the biochemicals produced by heat-treated MLO-Y4s. Taken together, these results elucidate the vital role of osteocytes in detecting and responding to thermal damage by means of thermally

  9. Expression of RANKL/OPG during bone remodeling in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, H., E-mail: [Department of Orthopedic Surgery, Yamaguchi Grand Medical Center, 77 Ohsaki, Hofu, Yamaguchi 747-8511 (Japan); Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); Mine, T. [Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Ogasa, H. [Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Taguchi, T. [Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Liang, C.T. [Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); National Health Research Institutes, Taipei 115, Taiwan (China)


    Highlights: {yields} This is the first study to determine the relationship between osteogenic differentiation and RANKL/OPG expression during bone remodeling in vivo. {yields} The OPG expression peak occurred during the bone formation phase, whereas the marked elevation of RANKL expression was observed during the bone resorption phase. {yields} Histological analysis showed that RANKL/OPG immunoreactivity was predominantly associated with bone marrow cells in the marrow cavity. {yields} The present study confirmed that RANKL/OPG are key factors linking bone formation to resorption during the bone remodeling process. -- Abstract: The interaction between receptor activator of nuclear factor {kappa}B ligand (RANKL) and osteoprotegerin (OPG) plays a dominant role in osteoclastogenesis. As both proteins are produced by osteoblast lineage cells, they are considered to represent a key link between bone formation and resorption. In this study, we investigated the expression of RANKL and OPG during bone remodeling in vivo to determine the relationship between osteoclastogenic stimulation and osteoblastic differentiation. Total RNA was prepared from rat femurs after marrow ablation on days 0, 3, 6, and 9. The temporal activation patterns of osteoblast-related genes (procollagen {alpha}1 (I), alkaline phosphatase, osteopontin, and osteocalcin) were examined by Northern blot analysis. An appreciable increase in the expression of these osteoblast markers was observed on day 3. The peak increase in gene expression was observed on day 6 followed by a slight reduction by day 9. Real-time PCR analysis showed that the OPG mRNA expression was markedly upregulated on day 6 and slightly decreased on day 9. In contrast, RANKL mRNA expression was increased by more than 20-fold on day 9. The RANKL/OPG ratio, an index of osteoclastogenic stimulation, peaked on day 9. Histological analysis showed that RANKL and OPG immunoreactivity were predominantly associated with bone marrow cells. The

  10. ATP-Dependent Chromatin Remodeling Factors and Their Roles in Affecting Nucleosome Fiber Composition

    Directory of Open Access Journals (Sweden)

    Alexandra Lusser


    Full Text Available ATP-dependent chromatin remodeling factors of the SNF2 family are key components of the cellular machineries that shape and regulate chromatin structure and function. Members of this group of proteins have broad and heterogeneous functions ranging from controlling gene activity, facilitating DNA damage repair, promoting homologous recombination to maintaining genomic stability. Several chromatin remodeling factors are critical components of nucleosome assembly processes, and recent reports have identified specific functions of distinct chromatin remodeling factors in the assembly of variant histones into chromatin. In this review we will discuss the specific roles of ATP-dependent chromatin remodeling factors in determining nucleosome composition and, thus, chromatin fiber properties.

  11. RosettaRemodel: a generalized framework for flexible backbone protein design.

    Directory of Open Access Journals (Sweden)

    Po-Ssu Huang

    Full Text Available We describe RosettaRemodel, a generalized framework for flexible protein design that provides a versatile and convenient interface to the Rosetta modeling suite. RosettaRemodel employs a unified interface, called a blueprint, which allows detailed control over many aspects of flexible backbone protein design calculations. RosettaRemodel allows the construction and elaboration of customized protocols for a wide range of design problems ranging from loop insertion and deletion, disulfide engineering, domain assembly, loop remodeling, motif grafting, symmetrical units, to de novo structure modeling.

  12. Prevalence and predictors of ventricular remodeling after anterior myocardial infarction in the era of modern medical therapy. (United States)

    Farah, Elaine; Cogni, Ana Lucia; Minicucci, Marcos F; Azevedo, Paula S; Okoshi, Katashi; Matsubara, Beatriz B; Zanati, Silméia G; Haggeman, Rodrigo; Paiva, Sergio A R; Zornoff, Leonardo A M


    The consequences of aggressive therapy following a myocardial infarction (MI) on ventricular remodeling are not well established. Thus, the objective of this study was to analyze the prevalence, clinical characteristics, and predictors of left ventricular remodeling in the era of modern medical therapy. Clinical characteristics and echocardiographic data were analyzed in 66 consecutive patients with anterior infarction at admission and at 6-month follow-up. Ventricular remodeling was defined as an increase of 10% in ventricular end-systolic or end-diastolic diameter. In our study, 58% of patients presented with ventricular remodeling. Patients with remodeling possessed higher total plasma creatine kinase (CPK), MB-fraction (CPK-MB), heart rate, heart failure, shortness of breath, and reperfusion therapy than patients without remodeling. In contrast, patients with remodeling had a smaller ejection fraction, E-Wave deceleration time (EDT), and early (E' Wave) and late (A' Wave) diastolic mitral annulus velocity (average of septal and lateral walls), but a higher E/E' than patients without remodeling. Patients with remodeling used more diuretics, digoxin, oral anticoagulants and aldosterone antagonists than patients without remodeling. In the multivariate analyses, only E' Wave was an independent predictor of ventricular remodeling. Each 1 unit increase in the E' Wave was associated with a 59% increased odds of ventricular remodeling. In patients with anterior MI, despite contemporary treatment, ventricular remodeling is still a common event. In addition, diastolic function can have an important role as a predictor of remodeling in this scenario.

  13. Multiple modes of chromatin remodeling by Forkhead box proteins. (United States)

    Lalmansingh, Avin S; Karmakar, Sudipan; Jin, Yetao; Nagaich, Akhilesh K


    Forkhead box (FOX) proteins represent a large family of transcriptional regulators unified by their DNA binding domain (DBD) known as a 'forkhead' or 'winged helix' domain. Over 40 FOX genes have been identified in the mammalian genome. FOX proteins share significant sequence similarities in the DBD which allow them to bind to a consensus DNA response element. However, their modes of action are quite diverse as they regulate gene expression by acting as pioneer factors, transcription factors, or both. This review focuses on the mechanisms of chromatin remodeling with an emphasis on three sub-classes-FOXA, FOXO, and FOXP members. FOXA proteins serve as pioneer factors to open up local chromatin structure and thereby increase accessibility of chromatin to factors regulating transcription. FOXP proteins, in contrast, function as classic transcription factors to recruit a variety of chromatin modifying enzymes to regulate gene expression. FOXO proteins represent a hybrid subclass having dual roles as pioneering factors and transcription factors. A subset of FOX proteins interacts with condensed mitotic chromatin and may function as 'bookmarking' agents to maintain transcriptional competence at specific genomic sites. The overall diversity in chromatin remodeling function by FOX proteins is related to unique structural motifs present within the DBD flanking regions that govern selective interactions with core histones and/or chromatin coregulatory proteins. This article is part of a Special Issue entitled: Chromatin in time and space. Published by Elsevier B.V.

  14. Biochemical markers of myocardial remodelling in hypertensive heart disease. (United States)

    González, Arantxa; López, Begoña; Ravassa, Susana; Beaumont, Javier; Arias, Teresa; Hermida, Nerea; Zudaire, Amaia; Díez, Javier


    The intricate mechanisms responsible for the structural remodelling of the myocardium that facilitates the evolution to heart failure in hypertensive patients, namely in those with left ventricular hypertrophy, requires from clinicians the utilization of a multibiomarker approach for short-term and long-term stratification as well as prognostication of patients. Biochemical markers may also help to identify patients with no clinical evidence of hypertensive heart disease, and provide information about the need for more aggressive therapy during different stages of the disease, and potentially provide valuable biochemical data for the specialist. Although there is a continuous and complex interplay between biochemical and imaging markers, perhaps their use will also have the potential to modify the medical management of patients with hypertensive heart disease and therapeutic decision-making by tailoring a targeted therapy according to the predominant mechanism of myocardial remodelling. This article will review in brief the most relevant information on a panel of circulating molecules that may accomplish the criteria required to be considered as biochemical markers of the cardiomyocyte and non-cardiomyocyte structural changes that occur in the hypertensive myocardium.

  15. Azithromycin ameliorates airway remodeling via inhibiting airway epithelium apoptosis. (United States)

    Liu, Yuanqi; Pu, Yue; Li, Diandian; Zhou, Liming; Wan, Lihong


    Azithromycin can benefit treating allergic airway inflammation and remodeling. In the present study, we hypothesized that azithromycin alleviated airway epithelium injury through inhibiting airway epithelium apoptosis via down regulation of caspase-3 and Bax/Bcl2 ratio in vivo and in vitro. Ovalbumin induced rat asthma model and TGF-β1-induced BEAS-2B cell apoptosis model were established, respectively. In vivo experiments, airway epithelium was stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to histologically evaluate the airway inflammation and remodeling. Airway epithelium apoptotic index (AI) was further analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), while expression of apoptosis related gene (Bax, Bcl2, Caspase-3) in lungs were measured by qRT-PCR and western blotting, respectively. In vitro experiments, apoptosis were evaluated by Flow cytometry (FCM) and TUNEL. Above apoptosis related gene were also measured by qRT-PCR and western blotting. Compared with the OVA group, azithromycin significantly reduced the inflammation score, peribronchial smooth muscle layer thickness, epithelial thickening and goblet cell metaplasia (Pazithromycin-treated rats (Pazithromycin significantly suppressed TGF-β1-induced BEAS-2B cells apoptosis (PAzithromycin is an attractive treatment option for reducing airway epithelial cell apoptosis by improving the imbalance of Bax/Bcl-2 ratio and inhibiting Caspase-3 level in airway epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Adipose extracellular matrix remodelling in obesity and insulin resistance☆ (United States)

    Lin, De; Chun, Tae-Hwa; Kang, Li


    The extracellular matrix (ECM) of adipose tissues undergoes constant remodelling to allow adipocytes and their precursor cells to change cell shape and function in adaptation to nutritional cues. Abnormal accumulation of ECM components and their modifiers in adipose tissues has been recently demonstrated to cause obesity-associated insulin resistance, a hallmark of type 2 diabetes. Integrins and other ECM receptors (e.g. CD44) that are expressed in adipose tissues have been shown to regulate insulin sensitivity. It is well understood that a hypoxic response is observed in adipose tissue expansion during obesity progression and that hypoxic response accelerates fibrosis and inflammation in white adipose tissues. The expansion of adipose tissues should require angiogenesis; however, the excess deposition of ECM limits the angiogenic response of white adipose tissues in obesity. While recent studies have focused on the metabolic consequences and the mechanisms of adipose tissue expansion and remodelling, little attention has been paid to the role played by the interaction between peri-adipocyte ECM and their cognate cell surface receptors. This review will address what is currently known about the roles played by adipose ECM, their modifiers, and ECM receptors in obesity and insulin resistance. Understanding how excess ECM deposition in the adipose tissue deteriorates insulin sensitivity would provide us hints to develop a new therapeutic strategy for the treatment of insulin resistance and type 2 diabetes. PMID:27179976

  17. Embryonic multipotent progenitors remodel the Drosophila airways during metamorphosis. (United States)

    Pitsouli, Chrysoula; Perrimon, Norbert


    Adult structures in holometabolous insects such as Drosophila are generated by groups of imaginal cells dedicated to the formation of different organs. Imaginal cells are specified in the embryo and remain quiescent until the larval stages, when they proliferate and differentiate to form organs. The Drosophila tracheal system is extensively remodeled during metamorphosis by a small number of airway progenitors. Among these, the spiracular branch tracheoblasts are responsible for the generation of the pupal and adult abdominal airways. To understand the coordination of proliferation and differentiation during organogenesis of tubular organs, we analyzed the remodeling of Drosophila airways during metamorphosis. We show that the embryonic spiracular branch tracheoblasts are multipotent cells that express the homeobox transcription factor Cut, which is necessary for their survival and normal development. They give rise to three distinct cell populations at the end of larval development, which generate the adult tracheal tubes, the spiracle and the epidermis surrounding the spiracle. Our study establishes the series of events that lead to the formation of an adult tubular structure in Drosophila.


    Klisch, Stephen M.; Asanbaeva, Anna; Oungoulian, Sevan R.; Masuda, Koichi; Thonar, Eugene J-MA; Davol, Andrew; Sah, Robert L.


    A cartilage growth mixture (CGM) model is proposed to address limitations of a model used in a previous study. New stress constitutive equations for the solid matrix are derived and collagen (COL) remodeling is incorporated into the CGM model by allowing the intrinsic COL material constants to evolve during growth. An analytical validation protocol based on experimental data from a recent in vitro growth study is developed. Available data included measurements of tissue volume, biochemical composition, and tensile modulus for bovine calf articular cartilage (AC) explants harvested at three depths and incubated for 13 days in 20% FBS and 20% FBS+β-aminopropionitrile. The proposed CGM model can match tissue biochemical content and volume exactly while predicting theoretical values of tensile moduli that do not significantly differ from experimental values. Also, theoretical values of a scalar COL remodeling factor are positively correlated with COL crosslink content, and mass growth functions are positively correlated with cell density. The results suggest that the CGM model may help to guide in vitro growth protocols for AC tissue via the a priori prediction of geometric and biomechanical properties. PMID:18532855

  19. Cell Wall Composition, Biosynthesis and Remodeling during Pollen Tube Growth

    Directory of Open Access Journals (Sweden)

    Jean-Claude Mollet


    Full Text Available The pollen tube is a fast tip-growing cell carrying the two sperm cells to the ovule allowing the double fertilization process and seed setting. To succeed in this process, the spatial and temporal controls of pollen tube growth within the female organ are critical. It requires a massive cell wall deposition to promote fast pollen tube elongation and a tight control of the cell wall remodeling to modify the mechanical properties. In addition, during its journey, the pollen tube interacts with the pistil, which plays key roles in pollen tube nutrition, guidance and in the rejection of the self-incompatible pollen. This review focuses on our current knowledge in the biochemistry and localization of the main cell wall polymers including pectin, hemicellulose, cellulose and callose from several pollen tube species. Moreover, based on transcriptomic data and functional genomic studies, the possible enzymes involved in the cell wall remodeling during pollen tube growth and their impact on the cell wall mechanics are also described. Finally, mutant analyses have permitted to gain insight in the function of several genes involved in the pollen tube cell wall biosynthesis and their roles in pollen tube growth are further discussed.

  20. Cell-cell junctional mechanotransduction in endothelial remodeling. (United States)

    Dorland, Yvonne L; Huveneers, Stephan


    The vasculature is one of the most dynamic tissues that encounter numerous mechanical cues derived from pulsatile blood flow, blood pressure, activity of smooth muscle cells in the vessel wall, and transmigration of immune cells. The inner layer of blood and lymphatic vessels is covered by the endothelium, a monolayer of cells which separates blood from tissue, an important function that it fulfills even under the dynamic circumstances of the vascular microenvironment. In addition, remodeling of the endothelial barrier during angiogenesis and trafficking of immune cells is achieved by specific modulation of cell-cell adhesion structures between the endothelial cells. In recent years, there have been many new discoveries in the field of cellular mechanotransduction which controls the formation and destabilization of the vascular barrier. Force-induced adaptation at endothelial cell-cell adhesion structures is a crucial node in these processes that challenge the vascular barrier. One of the key examples of a force-induced molecular event is the recruitment of vinculin to the VE-cadherin complex upon pulling forces at cell-cell junctions. Here, we highlight recent advances in the current understanding of mechanotransduction responses at, and derived from, endothelial cell-cell junctions. We further discuss their importance for vascular barrier function and remodeling in development, inflammation, and vascular disease.

  1. Cell Wall Composition, Biosynthesis and Remodeling during Pollen Tube Growth. (United States)

    Mollet, Jean-Claude; Leroux, Christelle; Dardelle, Flavien; Lehner, Arnaud


    The pollen tube is a fast tip-growing cell carrying the two sperm cells to the ovule allowing the double fertilization process and seed setting. To succeed in this process, the spatial and temporal controls of pollen tube growth within the female organ are critical. It requires a massive cell wall deposition to promote fast pollen tube elongation and a tight control of the cell wall remodeling to modify the mechanical properties. In addition, during its journey, the pollen tube interacts with the pistil, which plays key roles in pollen tube nutrition, guidance and in the rejection of the self-incompatible pollen. This review focuses on our current knowledge in the biochemistry and localization of the main cell wall polymers including pectin, hemicellulose, cellulose and callose from several pollen tube species. Moreover, based on transcriptomic data and functional genomic studies, the possible enzymes involved in the cell wall remodeling during pollen tube growth and their impact on the cell wall mechanics are also described. Finally, mutant analyses have permitted to gain insight in the function of several genes involved in the pollen tube cell wall biosynthesis and their roles in pollen tube growth are further discussed.

  2. BRCA1 Reflects Myocardial Adverse Remodeling in Idiopathic Dilated Cardiomyopathy. (United States)

    Nozynski, J K; Konecka-Mrowka, D; Zakliczynski, M; Zembala-Nozynska, E; Lange, D; Zembala, M


    The role of BRCA1 in chronic ischemic episodes seems to be pivotal for adverse remodeling and development of ischemic cardiomyopathy, because of its role in DNA repair and apoptosis. The aim of this study was to investigate the role of BRCA-1 in idiopathic dilated cardiomyopathy (IDCM). The study group (IDCM) comprised myocardial samples from hearts explanted before transplantation owing to IDCM in 10 males (age 44 ± 5.3 years) without clinical symptoms of ischemic heart disease. The control group consisted myocardial fragments taken from 10 male heart valve and pulmonary artery donors with diagnosed cerebral death (age 40 ± 2.3 years). BRCA1 was detected immunohistochemically with rabbit anti-BRCA1 polyclonal antibody. The intensity of BRCA1 expression was semiquantitatively assessed for cardiocytes, small vessels including capillaries, and interstitial cells. The significances between groups were estimated using the Mann-Whitney U test. All IDCM cases were positive and presented nonuniform BRCA1 expression: hypertrophied cardiocytes showed very intense staining and typical cardiomyopathic cardiocytes were stained weakly forming mosaic. Control cases showed weak-to-moderate uniform staining. Intensity of staining was significantly higher in IDCM cardiocytes, whereas small vessels and interstitial were stained similarly in both groups. IDCM adverse remodeling results in more intense but nonuniform BRCA1 expression. This phenomenon seems to reflect IDCM biology: lower BRCA1 expression in myocytes with lower anti-apoptotic and DNA damage repair activity, with the opposite in hypertrophied myofibers. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Computer simulation of ECG manifestations of left ventricular electrical remodeling. (United States)

    Bacharova, Ljuba; Szathmary, Vavrinec; Potse, Mark; Mateasik, Anton


    An increased QRS voltage is considered to be specific for the electrocardiogram (ECG) diagnosis of left ventricular hypertrophy (LVH). However, the QRS-complex patterns in patients with LVH cover a broader spectrum: increased QRS voltage, prolonged QRS duration, left axis deviation, and left anterior fascicular block- and left bundle branch block-like patterns, as well as pseudo-normal QRS patterns. The classical interpretation of the QRS patterns in LVH relates these changes to increased left ventricular mass (LVM) per se, while tending to neglect the modified active and passive electrical properties of the myocardium. However, it has been well documented that both active and passive electrical properties in LVH are altered. Using computer simulations, we have shown that an increased LVM is not the only determinant of QRS complex changes in LVH, as these changes could also be produced without changing the left ventricular mass, implying that these QRS patterns can be present in patients before their LVM exceeds the arbitrary upper normal limits. Our results link the experimental evidence on electrical remodeling with clinical interpretation of ECG changes in patients with LVH and stress the necessity of a complex interpretation of the QRS patterns considering both spatial and nonspatial determinants in terms of the spatial angle theory. We assume that hypertrophic electrical remodeling in combination with changes in left ventricular size and shape explains the variety of ECG patterns as well as the discrepancies between ECG and left ventricular mass. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Extracellular matrix remodeling derangement in ex-obese patients. (United States)

    Prist, Iryna Hirata; Salles, Alessandra Grassi; de Lima, Thais Martins; Modolin, Miguel Luiz Antônio; Gemperli, Rolf; Souza, Heraldo Possolo


    A known consequence of the large weight loss after bariatric surgery is the appearance of large skinfolds, particularly in the abdomen region of the patients. The balance between the synthesis of extracellular matrix (ECM) components and their proteolysis, mainly by fibrinolytic systems and matrix metalloproteases (MMPs), may be disturbed in these patients. The causes underlying the deregulation of ECM remodeling that occurs in these patients are not, however, clear. We investigated molecular mechanisms responsible for this dysfunction of ECM remodeling process, comparing it to normal skin. Collagen types, MMP2 and MMP9 expression and activity, interleukins 1β (IL1β) and 6 (IL6), and transcription coactivator PGC-1β expression were analyzed in 16 patients. Ex-obese patients presented increased expression of collagen types III and IV mRNA, increased expression of MMP2, decreased expression and activity of MMP9, and increased expression of PGC-1β in the skin. Inflammation markers IL1β and IL6 mRNA were not different. We have demonstrated that obese patients with extensive weight loss after bariatric surgery have increased expression of PGC-1β in the skin, which can result in a decreased expression and activity of MMP9 and increased collagen types III and IV deposition. These molecular changes may contribute for the formation of saggy skinfolds observed in these patients and impair wound healing.

  5. Mitochondrial Remodeling in Chicken Induced Pluripotent Stem-Like Cells. (United States)

    Choi, Hyun Woo; Kim, Jong Soo; Choi, Sol; Ju Hong, Yean; Byun, Sung June; Seo, Han Geuk; Do, Jeong Tae


    Chicken pluripotent stem cells (PSCs), such as embryonic stem cells and blastoderm cells, have been used to study development and differentiation in chicken. However, chicken PSCs are not widely used because they are hard to maintain in long-term culture. Recent reports suggest that chicken somatic cells can be reprogrammed to pluripotent state by defined factors to form induced pluripotent stem cells (iPSCs). These chicken iPSCs showed pluripotent differentiation potential and could be maintained in long-term culture. However, intracytoplasmic remodeling during reprogramming of chicken cells remains largely unknown. In this study, we generated chicken iPS-like cells (ciPSLCs) from chicken embryonic fibroblasts using a retroviral expression system encoding human reprogramming factors. These ciPSLCs could be maintained for more than 10 passages and expressed the endogenous chicken pluripotency markers, cNonog and cSox2. Moreover, the ciPSLCs showed higher nucleus to cytoplasm ratio and contained globular mitochondria with immature cristae. This morphology was similar to that of mammalian PSCs, but different from that of avian somatic cells, which showed lower nucleus to cytoplasm ratio and mature mitochondria. These results suggest that intracytoplasmic organelles in differentiated somatic cells could be successfully remodeled into the pluripotent state during reprogramming in chicken.

  6. Remodeling in the ischemic heart: the stepwise progression for heart

    Directory of Open Access Journals (Sweden)

    J.G. Mill


    Full Text Available Abstract Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI has decreased in the last decades. However, the incidence of heart failure (HF in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

  7. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Pier Andrea Nicolosi


    Full Text Available Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc. The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment.

  8. NAP1L1 accelerates activation and decreases pausing to enhance nucleosome remodeling by CSB. (United States)

    Lee, Ju Yeon; Lake, Robert J; Kirk, Jaewon; Bohr, Vilhelm A; Fan, Hua-Ying; Hohng, Sungchul


    Cockayne syndrome protein B (CSB) belongs to the SWI2/SNF2 ATP-dependent chromatin remodeler family, and CSB is the only ATP-dependent chromatin remodeler essential for transcription-coupled nucleotide excision DNA repair. CSB alone remodels nucleosomes ∼10-fold slower than the ACF remodeling complex. Strikingly, NAP1-like histone chaperones interact with CSB and greatly enhance CSB-mediated chromatin remodeling. While chromatin remodeling by CSB and NAP1-like proteins is crucial for efficient transcription-coupled DNA repair, the mechanism by which NAP1-like proteins enhance chromatin remodeling by CSB remains unknown. Here we studied CSB's DNA-binding and nucleosome-remodeling activities at the single molecule level in real time. We also determined how the NAP1L1 chaperone modulates these activities. We found that CSB interacts with DNA in two principle ways: by simple binding and a more complex association that involves gross DNA distortion. Remarkably, NAP1L1 suppresses both these interactions. Additionally, we demonstrate that nucleosome remodeling by CSB consists of three distinct phases: activation, translocation and pausing, similar to ACF. Importantly, we found that NAP1L1 promotes CSB-mediated remodeling by accelerating both activation and translocation. Additionally, NAP1L1 increases CSB processivity by decreasing the pausing probability during translocation. Our study, therefore, uncovers the different steps of CSB-mediated chromatin remodeling that can be regulated by NAP1L1. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis. (United States)

    Langdahl, Bente; Ferrari, Serge; Dempster, David W


    The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that

  10. Supramolecular organization of thylakoid membrane proteins in green plants

    NARCIS (Netherlands)

    Dekker, Jan P.; Boekema, Egbert J.


    The light reactions of photosynthesis in green plants are mediated by four large protein complexes, embedded in the thylakoid membrane of the chloroplast. Photosystem I (PSI) and Photosystem II (PSII) are both organized into large supercomplexes with variable amounts of membrane-bound peripheral

  11. Relationship between self-reported residential indoor remodeling and semen quality: a case-control study

    Directory of Open Access Journals (Sweden)

    Mao-Hua Miao


    Full Text Available The present study examined the association between residential indoor remodeling and poor semen quality. Sperm donors aged 18-45 years old were recruited in Shanghai, China. Semen specimens were collected and analyzed. An in-person interview was conducted to obtain information on the history of indoor remodeling and potential confounders. A total of 70 participants with abnormal semen quality (case group and 68 controls were examined. A total of 20 subjects reported indoor remodeling in the recent 24 months, and among them 17 subjects reported indoor remodeling in the recent 12 months. Compared with participants with no history of indoor remodeling, participants with a history of indoor remodeling in the recent 24 months were more than three times as likely to have poor sperm quality (adjusted odds ratio = 3.8, 95% confidence interval: 1.3-12.0 after controlling for potential confounders. The association was strengthened when the analysis was restricted to those who had indoor remodeling in the recent 12 months. Our findings provide preliminary evidence that indoor remodeling has an adverse effect on semen quality.

  12. Downregulation of β-Adrenoceptors in Isoproterenol-Induced Cardiac Remodeling through HuR.

    Directory of Open Access Journals (Sweden)

    Qian Yin

    Full Text Available β-adrenergic receptors (β-ARs play an important role in cardiac remodeling, which is the key pathological process in various heart diseases and leads to heart failure. However, the regulation of β-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of β1- and β2-AR expression in cardiac remodeling. The rat model of cardiac remodeling was established by subcutaneous injection of isoproterenol(ISO at the dose of 0.25 mg·kg(-1·d(-1 for 7 days. We found that the expression of β1- and β2-ARs decreased in the remodeling heart. The mechanisms may include the inhibition of DNA transcription and the increase of mRNA degradation. cAMP-response element binding protein(CREB is a well-known transcription factor of β-AR. However, the expression and activation of CREB was not changed in the remodeling heart. Further, human Antigen-R (HuR, a RNA binding protein, which binds to the 3'-untranslated region of the β-AR mRNA and promotes RNA degradation, was increased in the remodeling model. And in vitro, HuR deficiency reversed the reduction of β-AR mRNA induced by ISO. Therefore, the present findings indicate that HuR, but not CREB, is responsible for the reduction of β-AR expression in ISO induced cardiac remodeling.

  13. Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c

    NARCIS (Netherlands)

    Liu, Gang; Cooley, Marion A; Nair, Prema M; Donovan, Chantal; Hsu, Alan C; Jarnicki, Andrew G; Haw, Tatt Jhong; Hansbro, Nicole G; Ge, Qi; Brown, Alexandra C; Tay, Hock; Foster, Paul S; Wark, Peter A; Horvat, Jay C; Bourke, Jane E; Grainge, Chris L; Argraves, W Scott; Oliver, Brian G; Knight, Darryl A; Burgess, Janette K; Hansbro, Philip M


    Asthma is a chronic inflammatory disease of the airways. It is characterized by allergic airway inflammation, airway remodelling, and airway hyperresponsiveness (AHR). Asthma patients, in particular those with chronic or severe asthma, have airway remodelling that is associated with the accumulation

  14. Increased presence of capillaries next to remodeling sites in adult human cancellous bone

    DEFF Research Database (Denmark)

    Kristensen, Helene Bjoerg; Andersen, Thomas Levin; Marcussen, Niels


    Vascularization is a prerequisite for osteogenesis in a number of situations, including bone development, fracture healing, and cortical bone remodeling. It is unknown whether a similar link exists between cancellous bone remodeling and vascularization. Here, we show an association between remode...

  15. Can experimental data in humans verify the finite element-based bone remodeling algorithm?

    DEFF Research Database (Denmark)

    Wong, Christian; Gehrchen, P Martin; Kiaer, Thomas


    A finite element analysis-based bone remodeling study in human was conducted in the lumbar spine operated on with pedicle screws. Bone remodeling results were compared to prospective experimental bone mineral content data of patients operated on with pedicle screws....

  16. Predictors and prognostic value of left atrial remodelling after acute myocardial infarction

    DEFF Research Database (Denmark)

    Kyhl, Kasper; Vejlstrup, Niels; Lønborg, Jacob


    PURPOSE: Left atrial (LA) volume is a strong prognostic predictor in patients following ST-segment elevation myocardial infarction (STEMI). However, the change in LA volume over time (LA remodelling) following STEMI has been scarcely studied. We sought to identify predictors for LA remodelling an...

  17. Intravascular ultrasound assessment of remodelling and reference segment plaque burden in type-2 diabetic patients

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Thayssen, Per; Mintz, Gary S


    AIMS: Intravascular ultrasound (IVUS) assesses arterial remodelling by comparing the lesion external elastic membrane (EEM) with the reference segments; however, reference segments are rarely disease-free. The aim was to assess lesion and reference segment remodelling and plaque burden in patients...

  18. Liposome-encapsulated berberine treatment reduces adverse ventricle remodeling after myocardial infarction

    NARCIS (Netherlands)

    Wang, J.W.|info:eu-repo/dai/nl/413575055; Allijn, I.E.|info:eu-repo/dai/nl/369493192; Czarny, B.M.S.; Wang, X.Y.|info:eu-repo/dai/nl/413575152; Chong, S.Y.; Pastorin, G.; De Kleijn, D.P.V.; Storm, G.|info:eu-repo/dai/nl/073356328; Schiffelers, R.M.|info:eu-repo/dai/nl/212909509


    Introduction: Adverse left ventricle remodeling can be measured as a reduction in ejection fraction after myocardial infarction. Left ventricle remodeling leads to congestive heart failure and is a main determinant of mortality and morbidity after myocardial infarction. Berberine is an isoquinoline

  19. Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma

    NARCIS (Netherlands)

    Januskevicius, Andrius; Gosens, Reinoud; Sakalauskas, Raimundas; Vaitkiene, Simona; Janulaityte, Ieva; Halayko, Andrew J; Hoppenot, Deimante; Malakauskas, Kestutis


    Background: Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact

  20. The zebrafish as a model for tissue regeneration and bone remodelling

    NARCIS (Netherlands)

    Sharif, Faiza


    The aim of this thesis was to investigate the expression, and function of genes associated with remodelling and regeneration in the zebrafish model species. Here, we studied the role of cell populations, defined by their expression of markers, in bone regeneration and remodelling in zebrafish

  1. Transcriptome Remodeling of Acinetobacter baumannii during Infection and Treatment. (United States)

    Wright, Meredith S; Jacobs, Michael R; Bonomo, Robert A; Adams, Mark D


    Acinetobacter baumannii is an increasingly common multidrug-resistant pathogen in health care settings. Although the genetic basis of antibiotic resistance mechanisms has been extensively studied, much less is known about how genetic variation contributes to other aspects of successful infections. Genetic changes that occur during host infection and treatment have the potential to remodel gene expression patterns related to resistance and pathogenesis. Longitudinal sets of multidrug-resistant A. baumannii isolates from eight patients were analyzed by RNA sequencing (RNA-seq) to identify differentially expressed genes and link them to genetic changes contributing to transcriptional variation at both within-patient and population levels. The number of differentially expressed genes among isolates from the same patient ranged from 26 (patient 588) to 145 (patient 475). Multiple patients had isolates with differential gene expression patterns related to mutations in the pmrAB and adeRS two-component regulatory system genes, as well as significant differences in genes related to antibiotic resistance, iron acquisition, amino acid metabolism, and surface-associated proteins. Population level analysis revealed 39 genetic regions with clade-specific differentially expressed genes, for which 19, 8, and 3 of these could be explained by insertion sequence mobilization, recombination-driven sequence variation, and intergenic mutations, respectively. Multiple types of mutations that arise during infection can significantly remodel the expression of genes that are known to be important in pathogenesis.IMPORTANCE Health care-associated multidrug-resistant Acinetobacter baumannii can cause persistent infections in patients, but bacterial cells must overcome host defenses and antibiotic therapies to do so. Genetic variation arises during host infection, and new mutations are often enriched in genes encoding transcriptional regulators, iron acquisition systems, and surface

  2. Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

    DEFF Research Database (Denmark)

    Østrup, Olga; Hyttel, Poul; Klærke, Dan Arne


    complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract......Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression....... This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling...

  3. Kinetic proofreading of chromatin remodeling: from gene activation to gene repression and back

    Directory of Open Access Journals (Sweden)

    Raghvendra P Singh


    Full Text Available ATP-dependent chromatin remodeling is the active displacement of nucleosomes along or off DNA induced by chromatin remodeling complexes. This key process of gene regulation in eukaryote organisms has recently been argued to be controlled by a kinetic proofreading mechanism. In this paper we present a discussion of the current understanding of this process. We review the case of gene repression via heterochromatin formation by remodelers from the ISWI family and then discuss the activation of the IFN-β gene, where the displacement of the nucleosome is initiated by histone tail acetylations by the enzyme GCN5 which are required for the recruitment of SWI-SNF remodelers. We quantify the speci city of the acetylation step in the remodeling process by peptide docking simulations.

  4. A Poly-ADP-Ribose Trigger Releases the Auto-Inhibition of a Chromatin Remodeling Oncogene

    DEFF Research Database (Denmark)

    Singh, Hari R; Nardozza, Aurelio P; Möller, Ingvar R


    DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain with the ATP......DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain...... cancer mutants disrupt ALC1's auto-inhibition and activate chromatin remodeling. Our data show that the NAD+-metabolite and nucleic acid PAR triggers ALC1 to drive chromatin relaxation. Modular allostery in this oncogene tightly controls its robust, DNA-damage-dependent activation....

  5. Enhanced expression of fibroblast growth factors and receptor FGFR-1 during vascular remodeling in chronic obstructive pulmonary disease.

    NARCIS (Netherlands)

    Kranenburg, A.R.; Boer, W.I.; Krieken, J.H.J.M. van; Mooi, W.J.; Walters, J.E.; Saxena, P.R.; Sterk, P.J.; Sharma, H.S.


    Important characteristics of chronic obstructive pulmonary disease (COPD) include airway and vascular remodeling, the molecular mechanisms of which are poorly understood. We assessed the role of fibroblast growth factors (FGF) in pulmonary vascular remodeling by examining the expression pattern of

  6. Correlation between absence of bone remodeling compartment canopies, reversal phase arrest, and deficient bone formation in post-menopausal osteoporosis

    DEFF Research Database (Denmark)

    Levin Andersen, Thomas; Hauge, Ellen M; Rolighed, Lars


    Bone remodeling compartments (BRCs) were recently recognized to be present in patients with primary hyperparathyroidism and critical for bone reconstruction in multiple myeloma and endogenous Cushing's syndrome. The BRCs are outlined by a cellular canopy separating the bone remodeling events...

  7. Electrical remodeling and atrial dilation during atrial tachycardia are influenced by ventricular rate : Role of developing tachycardiomyopathy

    NARCIS (Netherlands)

    Schoonderwoerd, BA; Van Gelder, IC; Van Veldhuisen, DJ; Tieleman, RG; Grandjean, JG; Bel, KJ; Allessie, MA; Crijns, HJGM


    Atrial Remodeling in Tachycardiomyopathy. Introduction: Atrial fibrillation (AF) and congestive heart failure (CHF) are two clinical entities that often coincide. Our aim was to establish the influence of concomitant high ventricular rate and consequent development of CHF on electrical remodeling

  8. Enhanced expression of fibroblast growth factors and receptor FGFR-1 during vascular remodeling in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    A.R. Kranenburg (Andor); W.I. de Boer (Pim); J.H.J.M. van Krieken (Han); W.J. Mooi (Wolter); J.E. Walters (Jane); P.R. Saxena (Pramod Ranjan); P.J. Sterk (Peter); H.S. Sharma (Hari)


    textabstractImportant characteristics of chronic obstructive pulmonary disease (COPD) include airway and vascular remodeling, the molecular mechanisms of which are poorly understood. We assessed the role of fibroblast growth factors (FGF) in pulmonary vascular remodeling by

  9. Protein receptor-independent plasma membrane remodeling by HAMLET

    DEFF Research Database (Denmark)

    Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L.


    A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This "protein-centric" view is increasingly challenged by evidence for the involvement of specialized membrane domains...... in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range...... of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a "receptor independent" transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET...

  10. Trabecular bone structure and strength - remodelling and repair

    DEFF Research Database (Denmark)

    Mosekilde, Lis; Ebbesen, Ebbe Nils; Erikstrup, Lise Tornvig


    The strength of the spinal trabecular bone declines by a factor of 4-5 from the age of 20 to 80 years. At the same time, the volumetric (apparent) density declines by a factor of only 2. This discrepancy can be explained by the known power relationship between density and strength; this power...... by the remodelling process. 5) Bone material quality will slightly change, leading to a decrease in collagen content and a relative increase in the degree of mineralisation. But, it is not known how these factors will influence the power relationship between density and strength. Nor is it known how different......; and the hydraulic effect of the bone marrow. In order to answer these questions, more in vitro and in vivo studies on human bone in relation to aging, to immobilisation, to exercise and in relation to different treatment regimens are needed....

  11. The Role of Adipocytokines in Pancreatic Remodeling in Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    L.V. Zhuravliova


    Full Text Available The article analysed the data about the role of adipocytokines in pancreatic remodeling in chronic pancreatitis. Data, obtained by generalizing the current literature, enable to identify the role of some adipocytokines (apelin, tumor necrosis factor α in the development and progression of the pathophysiological processes in the pancreas, especially in regard to the mechanism of chronic pancreatitis. Adipocytokines being studied play a role in carbohydrate and lipid metabolism disorders, promote the induction of inflammation, tissue maladaptive hypertrophy, the onset of steatosis, fibrosis of the pancreas and have an impact on the various stages of the pathogenesis of chronic pancreatitis. We should pay close attention to the diagnostic role of cytokines that can help to develop new algorithms for non-invasive diagnosis of chronic pancreatitis.

  12. Retinoid signaling in pathological remodeling related to cardiovascular disease. (United States)

    Kotake, Daisuke; Sato, Taiki; Hirasawa, Noriyasu


    Retinoids, the active derivatives of vitamin A, are critical signaling molecules in crucial biological processes such as embryonic development, the maintenance of immune function, and cellular differentiation and proliferation. Preclinical studies have shown that retinoids also regulate morphological changes during the progression of cardiovascular disease (CVD). CVD is complexly formed in a mutual chain reaction of various modern lifestyle-related risk factors such as dyslipidemia, hypertension, diabetes, and obesity. These factors induce the pathological remodeling of adipose tissue, the vasculature, and the ventricles, which are a potential target for retinoid signaling. This perspective highlights emerging topics and future prospectives on the relationship between CVD and retinoid signaling. © 2013 Elsevier B.V. All rights reserved.

  13. Brassinosteroid Mediated Cell Wall Remodeling in Grasses under Abiotic Stress

    Directory of Open Access Journals (Sweden)

    Xiaolan Rao


    Full Text Available Unlike animals, plants, being sessile, cannot escape from exposure to severe abiotic stresses such as extreme temperature and water deficit. The dynamic structure of plant cell wall enables them to undergo compensatory changes, as well as maintain physical strength, with changing environments. Plant hormones known as brassinosteroids (BRs play a key role in determining cell wall expansion during stress responses. Cell wall deposition differs between grasses (Poaceae and dicots. Grass species include many important food, fiber, and biofuel crops. In this article, we focus on recent advances in BR-regulated cell wall biosynthesis and remodeling in response to stresses, comparing our understanding of the mechanisms in grass species with those in the more studied dicots. A more comprehensive understanding of BR-mediated changes in cell wall integrity in grass species will benefit the development of genetic tools to improve crop productivity, fiber quality and plant biomass recalcitrance.

  14. Remodelling of choroidal blood flow in radiation choroidopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Hideo; Muraoka, Kanemitsu; Takahashi, Kyoichi; Sutoh, Noriko [Gunma Univ., Maebashi (Japan). School of Medicine


    Two males, aged 68 and 34 years each, presented with radiation retinopathy. One had received radiation therapy to the whole brain for intracranial metastasis of lung carcinoma 29 months before. The other underwent surgery and radiation for melanoma of the upper eyelid 15 years before. When examined by indocyanine green angiography. both cases showed vasoocclusive changes in the choroid involving the choriocapillaris and major vessels in the affected fundus area. In one eye with severe retinal vascular lesions in the superior temporal quadrant, the vortex vein in the quadrant had obliterated. The venous blood in this quadrant was drained into the inferior temporal vortex vein crossing the presumed watershed zone temporal to the macula. Collaterals had formed between choroidal arteries and between choroidal veins. These cases illustrate that choroidal vascular lesions may be present in radiation retinopathy, that the former may be more pronounced than the latter and that choroidal vessels may undergo extensive remodelling to compensate for the disturbed choroidal circulation. (author)

  15. Intestinal remodelling in mink fed with reduced protein content

    DEFF Research Database (Denmark)

    Chen, Pengmin; Zhao, Jingbo; Nielsen, Vivi Hunnicke


    Low protein intake occurs in humans in relation to diseases, starvation and post-operatively. Low-protein diets may affect the gastrointestinal structure and mechanical function. The aim was to study the passive biomechanical properties and tissue remodelling of the intestine in minks on reduced...... protein diets. Twenty-seven male minks were divided into three groups receiving different protein level in the diet for 6 weeks: High protein level (group H, 55% energy from protein), moderate protein level (group M, 30% energy from protein) and low protein level (group L, 15% energy from protein) (n=9...... groups. Feeding the low-protein diet shifted the stress-strain curves to the right for the circumferential direction, indicating the wall become softer in the circumferential direction. However, no significant difference was observed in the longitudinal direction for any of the intestinal segments...

  16. Sliding and peeling of histone during chromatin remodelling

    CERN Document Server

    Garai, Ashok; Chowdhury, Debashish


    ATP-dependent chromatin remodeling enzymes (CRE) are bio-molecular motors in eukaryotic cells. These are driven by a chemical fuel, namely, adenosine triphosphate (ATP). CREs actively participate in many cellular processes that require accessibility of specific stretches of DNA which are packaged as chromatin. The basic unit of chromatin is a nucleosome where 146 bp $\\sim$ 50 nm of a double stranded DNA (dsDNA) is wrapped around a spool formed by histone proteins. We investigate the mechanism of peeling of the histone spool, and its complete detachment, from the dsDNA by a CRE. Our two-state model of a CRE captures effectively two distinct chemical (or conformational) states in the mechano-chemical cycle of each ATP-dependent CRE. We calculate the mean times for histone detachment. Our predictions on the ATP-dependence of the measurable quantities can be tested by carrying out {\\it in-vitro} experiments.

  17. Neural plasticity and network remodeling: From concepts to pathology. (United States)

    Cohen, Erez James; Quarta, Eros; Bravi, Riccardo; Granato, Alberto; Minciacchi, Diego


    Neuroplasticity has been subject to a great deal of research in the last century. Recently, significant emphasis has been placed on the global effect of localized plastic changes throughout the central nervous system, and on how these changes integrate in a pathological context. Specifically, alterations of network functionality have been described in various pathological contexts to which corresponding structural alterations have been proposed. However, considering the amount of literature and the different pathological contexts, an integration of this information is still lacking. In this paper we will review the concepts of neural plasticity as well as their repercussions on network remodeling and provide a possible explanation to how these two concepts relate to each other. We will further examine how alterations in different pathological contexts may relate to each other and will discuss the concept of plasticity diseases, its models and implications. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Multiphysics of bone remodeling: A 2D mesoscale activation simulation. (United States)

    Spingarn, C; Wagner, D; Rémond, Y; George, D


    In this work, we present an evolutive trabecular model for bone remodeling based on a boundary detection algorithm accounting for both biology and applied mechanical forces, known to be an important factor in bone evolution. A finite element (FE) numerical model using the Abaqus/Standard® software was used with a UMAT subroutine to solve the governing coupled mechanical-biological non-linear differential equations of the bone evolution model. The simulations present cell activation on a simplified trabeculae configuration organization with trabecular thickness of 200µm. For this activation process, the results confirm that the trabeculae are mainly oriented in the active direction of the principal mechanical stresses and according to the principal applied mechanical load directions. The trabeculae surface activation is clearly identified and can provide understanding of the different bone cell activations in more complex geometries and load conditions.

  19. Molecular Simulations of Actomyosin Network Self-Assembly and Remodeling (United States)

    Komianos, James; Popov, Konstantin; Papoian, Garegin; Papoian Lab Team

    Actomyosin networks are an integral part of the cytoskeleton of eukaryotic cells and play an essential role in determining cellular shape and movement. Actomyosin network growth and remodeling in vivo is based on a large number of chemical and mechanical processes, which are mutually coupled and spatially and temporally resolved. To investigate the fundamental principles behind the self-organization of these networks, we have developed a detailed mechanochemical, stochastic model of actin filament growth dynamics, at a single-molecule resolution, where the nonlinear mechanical rigidity of filaments and their corresponding deformations under internally and externally generated forces are taken into account. Our work sheds light on the interplay between the chemical and mechanical processes governing the cytoskeletal dynamics, and also highlights the importance of diffusional and active transport phenomena. Our simulations reveal how different actomyosin micro-architectures emerge in response to varying the network composition. Support from NSF Grant CHE-1363081.

  20. Epigenetic effects of chromatin remodeling agents on organotypic cultures. (United States)

    Sirchia, Silvia M; Faversani, Alice; Rovina, Davide; Russo, Maria V; Paganini, Leda; Savi, Federica; Augello, Claudia; Rosso, Lorenzo; Del Gobbo, Alessandro; Tabano, Silvia; Bosari, Silvano; Miozzo, Monica


    Tumor epigenetic defects are of increasing relevance to clinical practice, because they are 'druggable' targets for cancer therapy using chromatin-remodeling agents (CRAs). New evidences highlight the importance of the microenvironment on the epigenome regulation and the need to use culture models able to preserve tissue morphology, to better understand the action of CRAs. Methods & methods: We studied the epigenetic response induced by culturing and CRAs in a preclinical model, preserving ex vivo the original tissue microenvironment and morphology, assessing different epigenetic signatures. Our overall findings suggest that culturing and CRAs cause heterogeneous effects on the genes methylation; CRAs affect the global DNA methylation and can trigger an active DNA demethylation; the culture induces alterations in the histone deacetylase expression. Despite the limited number of cases, these findings can be considered a proof of concept of the possibility to test CRAs epigenetic effects on ex vivo tissues maintained in their native tissue architecture.

  1. The insight of mixtures theory for growth and remodeling (United States)

    Ambrosi, D.; Preziosi, L.; Vitale, G.


    The emergence of residual stress as due to growth and remodeling of soft biological tissues is considered in the framework of the mixture theory. The focus is on mixtures composed by one elastic solid component and several fluid ones. It is shown that the standard theory is unable to predict residual stresses unless enriched by a suitable descriptor of growth. Both the introduction of a dependence of the free energy on the density of the solid component and the Kroner-Lee multiplicative decomposition of the gradient of deformation are effective in this respect, with different levels of generality. When adopting a multiplicative decomposition of the tensor gradient of deformation, thermodynamical arguments suggest constitutive laws for the evolution of the growth tensor that point out the role of the concentration of fluid species in driving the emergence of residual stress thanks to inhomogeneous growth.

  2. Arachidonoyl-Phospholipid Remodeling in Proliferating Murine T Cells

    Directory of Open Access Journals (Sweden)

    Ando Soichiro


    Full Text Available Abstract Backgound Previous studies have shown that the functional capacity of T cells may be modulated by the composition of fatty acids within, and the release of fatty acids from membrane phospholipids, particulary containing arachidonic acid (AA. The remodeling of AA within membrane phospholipids of resting and proliferating CD4+ and CD8+ T cells is examined in this study. Results Splenic T cells were cultured in the presence or absence of anti-CD3 mAb for 48 h then labeled with [3H]AA for 20 min. In unstimulated cells, labeled AA was preferentially incorporated into the phosphoglycerides, phosphatidylcholine (PC followed by phosphatidylinositol (PI and phosphatidylethanolamine (PE. During a subsequent chase in unlabeled medium unstimulated CD4+ and CD8+ T cells demonstrated a significant and highly selective transfer of free, labeled AA into the PC pool. In contrast, proliferating CD4+ and CD8+ T cells distributed labeled [3H]AA predominantly into PI followed by PC and PE. Following a chase in AA-free medium, a decline in the content of [3H]AA-PC was observed in association with a comparable increase in [3H]AA-PE. Subsequent studies revealed that the cold AA content of all PE species was increased in proliferating T cells compared with that in non-cycling cells, but that enrichment in AA was observed only in the ether lipid fractions. Finally, proliferating T cells preincubated with [3H]AA exhibited a significant loss of labeled arachidonate in the PC fraction and an equivalent gain in labeled AA in 1-alk-1'-enyl-2-arachidonoyl-PE during a chase in unlabeled medium. Conclusion This apparent unidirectional transfer of AA from PC to ether-containing PE suggests the existence of a CoA-independent transacylase system in T cells and supports the hypothesis that arachidonoyl phospholipid remodeling may play a role in the regulation of cellular proliferation.

  3. Quantitative Estimates of Bio-Remodeling on Coastal Rock Surfaces

    Directory of Open Access Journals (Sweden)

    Marta Pappalardo


    Full Text Available Remodeling of rocky coasts and erosion rates have been widely studied in past years, but not all the involved processes acting over rocks surface have been quantitatively evaluated yet. The first goal of this paper is to revise the different methodologies employed in the quantification of the effect of biotic agents on rocks exposed to coastal morphologic agents, comparing their efficiency. Secondly, we focus on geological methods to assess and quantify bio-remodeling, presenting some case studies in an area of the Mediterranean Sea in which different geological methods, inspired from the revised literature, have been tested in order to provide a quantitative assessment of the effects some biological covers exert over rocky platforms in tidal and supra-tidal environments. In particular, different experimental designs based on Schmidt hammer test results have been applied in order to estimate rock hardness related to different orders of littoral platforms and the bio-erosive/bio-protective role of Chthamalus ssp. and Verrucariaadriatica. All data collected have been analyzed using statistical tests to evaluate the significance of the measures and methodologies. The effectiveness of this approach is analyzed, and its limits are highlighted. In order to overcome the latter, a strategy combining geological and experimental–computational approaches is proposed, potentially capable of revealing novel clues on bio-erosion dynamics. An experimental-computational proposal, to assess the indirect effects of the biofilm coverage of rocky shores, is presented in this paper, focusing on the shear forces exerted during hydration-dehydration cycles. The results of computational modeling can be compared to experimental evidence, from nanoscopic to macroscopic scales.

  4. [Cardiac dyssynchrony correlates with left ventricular remodeling after myocardial Infarction]. (United States)

    McNab, Paul; Castro, Pablo; Gabrielli, Luigi; Verdejo, Hugo; Quintana, Juan Carlos; Rodríguez, José A; Corbalán, Ramón


    Cardiac dyssynchrony is common in advanced heart failure (HF), but the changes in cardiac synchrony after myocardial infarction (MI) have not been adequately descríbed. To study the relationship between cardiac synchrony and left ventricular remodeling after acute myocardial infarction. Forty nine patients aged 59+/-10 years (77% men) with a first episode of a ST segment elevation MI, were studied. Scintigraphic left ventricular function and synchrony analyses were performed at baseline and after a six months follow-up. Determinations were compared with 33 healthy subjects. At baseline, patients with MIhad a decreased left ventricular ejection fraction (LVEF) and significant dyssynchrony, when compared with controls. LVEF was 36.4%+/-10%, left ventricular end-diastolic volume (LVEDV) 127+/-38 mL, interventricular delay (IEV) 29+/-35 miliseconds (ms), and intraventricular delay (IAV), 234+/-89 ms. After 6 months, LVEF significantly improved (38%+/-10%, p =0.042) without significant changes in LVEDV (129+/-32 mL, p =0.97), IEV (24+/-17, p =0.96) or IAV (231+/-97, p =0.34). At baseline there were significant correlations between IAV and LVEF, and between IAV and LVEDV (r =0.48, p =0.001 and r =0.41, p =0.004, respectively). These correlations remained significant after 6 months. There was a positive correlation between IAV and LVEDV changes at six months (r =0.403, p =0.04). The development of cardiac dyssynchrony correlates with adverse left ventricular remodeling after MI .

  5. Remodeling of the thoracic aorta after bone marrow cell transplantation (United States)

    Felix, Alyne; Monteiro, Nemesis; Rocha, Vinícius Novaes; Oliveira, Genilza; Moraes, Alan Cesar; Andrade, Cherley; Nascimento, Ana Lucia; de Carvalho, Laís; Thole, Alessandra; Carvalho, Jorge


    Stem cells are characterized by their ability to differentiate into multiple cell lineages and display the paracrine effect. The aim of this work was to evaluate the effect of therapy with bone marrow cells (BMCs) on blood glucose, lipid metabolism and aortic wall remodeling in mice through the administration of a high fat diet and subsequent BMCs transplantation. C57BL/6 mice were fed a control diet (CO group) or an atherogenic diet (AT group). After 16 weeks, the AT group was divided into four groups: an AT 14 days group and AT 21 days group, that were given an injection of vehicle and sacrificed at 14 and 21 days after, respectively; AT-BMC 14 days group and AT-BMC 21 days group that was given an injection of BMCs and sacrificed at 14 and 21 days after. The CO group was sacrificed along with other groups. The BMCs transplant had reduced blood glucose, triglycerides and total cholesterol. The Qa (1/mm2) was quantitatively reduced in AT 14 days group, AT 21 days group and was high in AT-BMC 21 days group. The AT 21 days group exhibited increased tunica media and elastic system fibers. The immunolabeling for α-SMA and VEGF showed less immunolabeling in transplanted groups with BMCs. The immunostaining for PCNA seems to be more expressive in the group AT-BMC 21 days group. To conclude, our results support the concept that in mice, the injection of BMCs improve glucose levels, lipid metabolism and remodeling of the aortic wall in animals using atherogenic diet. PMID:25337194

  6. Electrical remodelling in patients with iatrogenic left bundle branch block. (United States)

    Engels, Elien B; Poels, Thomas T; Houthuizen, Patrick; de Jaegere, Peter P T; Maessen, Jos G; Vernooy, Kevin; Prinzen, Frits W


    Left bundle branch block (LBBB) is induced in approximately one-third of all transcatheter aortic valve implantation (TAVI) procedures. We investigated electrophysiological remodelling in patients with TAVI-induced LBBB. This retrospective study comprises 107 patients with initially narrow QRS complex of whom 40 did not and 67 did develop persistent LBBB after TAVI. 12-lead electrocardiograms (ECGs) taken before TAVI, within 24 hours ('acute'), and 1-12 months after TAVI ('chronic') were used to reconstruct vectorcardiograms. From these vectorcardiograms, QRS and T-wave area were calculated as comprehensive indices of depolarization and repolarization abnormalities, respectively. TAVI-induced LBBB resulted in significant acute depolarization and repolarization changes while further repolarization changes were observed with longer lasting LBBB. The amount of long-term repolarization changes (remodelling) was highly variable between patients. The change in T-wave area between acute and chronic LBBB ranged from +57% to - 77%. After dividing the LBBB cohort into tertiles based on the change in T-wave area, only baseline QRS area was larger in the tertile with no significant change in T-wave area. During longer lasting LBBB, the spatial vector gradient (SVG) changed orientation towards the direction of the QRS-vector, indicating that later-activated regions developed shorter action potential duration. This study in patients with TAVI-induced LBBB shows that repolarization changes develop within months after onset of LBBB, and that these changes are highly variable between individual patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email:

  7. Electrocardiographic evidence of ventricular repolarization remodelling during atrial fibrillation. (United States)

    Tan, Hanno L; Smits, Jeroen P P; Loef, Arjan; Tanck, Michael W T; Hardziyenka, Maxim; Campian, Maria E


    Some atrial fibrillation (AF) patients develop excessive QTc prolongation and torsade de pointes when they take QTc-prolonging antiarrhythmic drugs (class IA/III) immediately after termination of AF. We hypothesized that this is caused by changes in ventricular repolarization during AF. We aimed to establish whether such 'ventricular repolarization remodelling' occurs. We studied all patients who visited our cardiac emergency room with AF and converted to sinus rhythm (SR) in a 30 months' period. We defined four groups: (i) no antiarrhythmic drugs, electrical cardioversion (n = 30), (ii) no antiarrhythmic drugs, spontaneous AF termination (n = 19), (iii) antiarrhythmic drugs, electrical cardioversion (n = 29), and (iv) antiarrhythmic drugs, spontaneous AF termination (n = 9). We studied QTc duration at SR before AF (SR(baseline)), immediately after termination of AF (SR(postAF)), and at follow-up (SR(followup): > or =7 days after SR(postAF)). Moreover, we studied determinants of QTc prolongation at SR(postAF). We found that, in all groups, QTc at SR(postAF) was significantly and transiently prolonged compared with SR(baseline). Although of limited magnitude on average (approximately 5%), the increase was substantial (approximately 15%) in some individuals. The only independent predictor of the magnitude of QTc prolongation was QTc duration at SR(baseline); this relation had a negative correlation. AF causes ventricular repolarization remodelling, resulting in QTc prolongation. QTc prolongation is substantial in some patients and may render these patients vulnerable to pro-arrhythmia from class IA/III antiarrhythmic drugs immediately after termination of AF.

  8. Interspecific differences in hypoxia-induced gill remodeling in carp. (United States)

    Dhillon, Rashpal S; Yao, Lili; Matey, Victoria; Chen, Bo-Jian; Zhang, An-Jie; Cao, Zhen-Dong; Fu, Shi-Jian; Brauner, Colin J; Wang, Yuxiang S; Richards, Jeffrey G


    The gills of many fish, but in particular those of crucian carp (Carassius carassius) and goldfish (Carassius auratus), are capable of extensive remodeling in response to changes in oxygen (O2), temperature, and exercise. In this study, we investigated the interspecific variation in hypoxia-induced gill modeling and hypoxia tolerance in 10 closely related groups of cyprinids (nine species, with two strains of Cyprinus carpio). There was significant variation in hypoxia tolerance, measured as the O2 tension (P(O2)) at which fish lost equilibrium (LOEcrit), among the 10 groups of carp. In normoxia, there was a significant, phylogenetically independent relationship between mass-specific gill surface area and LOEcrit, with the more hypoxia-tolerant carp having smaller gills than their less hypoxia-tolerant relatives. All groups of carp, except the Chinese bream (Megalobrama pellegrini), increased mass-specific gill surface area in response to 48 h of exposure to hypoxia (0.7 kPa) through reductions in the interlamellar cell mass (ILCM) volume. The magnitude of the hypoxia-induced reduction in the ILCM was negatively correlated with LOEcrit (and thus positively correlated with hypoxia tolerance), independent of phylogeny. The hypoxia-induced changes in gill morphology resulted in reduced variation in mass-specific gill surface area among species and eliminated the relationship between LOEcrit and mass-specific gill surface area. While behavioral responses to hypoxia differed among the carp groups, there were no significant relationships between hypoxia tolerance and the Po2 at which aquatic surface respiration (ASR) was initiated or the total number of ASR events observed during progressive hypoxia. Our results are the first to show that the extent of gill remodeling in cyprinids is associated with hypoxia tolerance in a phylogenetically independent fashion.

  9. Vernal keratoconjunctivitis: a severe allergic eye disease with remodeling changes. (United States)

    Vichyanond, Pakit; Pacharn, Punchama; Pleyer, Uwe; Leonardi, Andrea


    Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Conventional therapy for allergic conjunctivitis is generally not adequate for VKC. Pediatricians and allergists are often not familiar with the severe clinical symptoms and signs of VKC. As untreated VKC can lead to permanent visual loss, pediatric allergists should be aware of the management and therapeutic options for this disease to allow patients to enter clinical remission with the least side effects and sequelae. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. On examination, giant papillae are frequently observed on the upper tarsal conjunctiva (cobblestoning appearance), with some developing gelatinous infiltrations around the limbus surrounding the cornea (Horner-Trantas dot). Conjunctival injections are mostly severe with thick mucus ropy discharge. Eosinophils are the predominant cells found in the tears and eye discharge. Common therapies include topical antihistamines and dual-acting agents, such as lodoxamide and olopatadine. These are infrequently sufficient and topical corticosteroids are often required for the treatment of flare ups. Ocular surface remodeling leads to severe suffering and complications, such as corneal ulcers/scars. Other complications include side effects from chronic topical steroids use, such as increased intraocular pressure, glaucoma, cataract and infections. Alternative therapies for VKC include immunomodulators, such as cyclosporine A and tacrolimus. Surgery is reserved for those with complications and should be handled by ophthalmologists with special expertise. Newer research on the pathogenesis of VKC is reviewed in this article. Vernal keratoconjunctivitis is a very important allergic eye disease in children. Complications and remodeling changes are unique and can lead to blindness

  10. Early remodeling of rat cardiac muscle induced by swimming training

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    Verzola R.M.M.


    Full Text Available The aim of the present investigation was to study the effect of acute swimming training with an anaerobic component on matrix metallopeptidase (MMP activity and myosin heavy chain gene expression in the rat myocardium. Animals (male Wistar rats, weighing approximately 180 g were trained for 6 h/day in 3 sessions of 2 h each for 1 to 5 consecutive days (N = 5 rats per group. Rats swam in basins 47 cm in diameter and 60 cm deep filled with water at 33 to 35ºC. After the training period a significant increase (P < 0.05 was observed in the heart weight normalized to body weight by about 22 and 35% in the groups that trained for 96 and 120 h, respectively. Blood lactate levels were significantly increased (P < 0.05 in all groups after all training sessions, confirming an anaerobic component. However, lactate levels decreased (P < 0.05 with days of training, suggesting that the animals became adapted to this protocol. Myosin heavy chain-ß gene expression, analyzed by real time PCR and normalized with GAPDH gene expression, showed a significant two-fold increase (P < 0.01 after 5 days of training. Zymography analysis of myocardium extracts indicated a single ~60-kDa activity band that was significantly increased (P < 0.05 after 72, 96, and 120 h, indicating an increased expression of MMP-2 and suggesting precocious remodeling. Furthermore, the presence of MMP-2 was confirmed by Western blot analysis, but not the presence of MMP-1 and MMP-3. Taken together, our results indicate that in these training conditions, the rat heart undergoes early biochemical and functional changes required for the adaptation to the new physiological condition by tissue remodeling.

  11. Right ventricular remodeling in restrictive ventricular septal defect (United States)

    Monreal, Gretel; Youtz, Dane J.; Phillips, Alistair B.; Eyman, Mahala E.; Gorr, Matthew W.; Velten, Christina; Lucchesi, Pamela A.; Wold, Loren E.; Gerhardt, Mark A.


    Restrictive ventricular septal defect (rVSD) presents with little/no hemodynamic aberrations despite a patent septal defect. Clinically, these patients are observed with the hope that the defect will functionally close over time without the need for surgical repair and development of heart failure. Without evidence supporting a definitive therapeutic strategy, rVSD patients may have increased risk of a poor outcome. We tested the hypothesis that rVSD results in subclinical RV diastolic dysfunction and molecular remodeling. Five pigs underwent surgical rVSD creation. Echocardiography, hemodynamics, myocyte contractility experiments, and proteomics/Western blot were performed 6-weeks post-rVSD and in controls. *p < 0.05. LV and RV hemodynamics in rVSD were comparable to controls. The tricuspid valve early/late diastolic inflow velocity ratio (TV E/A ratio) decreased from 1.6 ± 0.05 in controls to 1.0 ± 0.08* in rVSD, indicating RV diastolic dysfunction. rVSD RV myocytes showed abnormalities in contraction (departure velocity (Vd) − 51%*, Vd time +55%*) and relaxation (return velocity (Vr) −50%*, Vr time +62%*). Mitochondrial proteins (fatty acid, TCA cycle) increased 2-fold*, indicating heightened RV work. Desmin protein upregulated 285%* in rVSD RV myocardium, suggesting cytoskeletal remodeling. rVSD causes RV diastolic dysfunction, myocyte functional impairment, and mitochondrial/cytoskeletal protein upregulation in our model. Desmin upregulation may hinder sarcomeric organization/relaxation, representing a key subclinical early marker for future RV dysfunction. TV E/A measurements are a non-invasive modality to assess rVSD patients for diastolic dysfunction. Translational research applications may lead to fundamental changes in the clinical management of rVSD by providing evidence for early repair of the defect. PMID:20637777

  12. Cells involved in extracellular matrix remodeling after acute myocardial infarction

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    Garcia, Larissa Ferraz [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Mataveli, Fábio D’Aguiar [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva [Universidade Federal de São Paulo, São Paulo, SP (Brazil)


    Evaluate the effects of VEGF{sub 165} gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF{sub 165} treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF{sub 165}. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF{sub 165}, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF{sub 165} seems to provide a protective effect in the treatment of acute myocardial infarct.

  13. Muscle metabolic remodelling in response to endurance exercise in salmonids

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    Andrea J Morash


    Full Text Available Phenotypic plasticity of skeletal muscle is relevant to swimming performance and metabolism in fishes, especially those that undergo extreme locomotory feats, such as seasonal migration. However, the influence of endurance exercise and the molecular mechanisms coordinating this remodelling are not well understood. The present study examines muscle metabolic remodelling associated with endurance exercise in fed rainbow trout as compared to migrating salmon. Trout were swum for 4 weeks at 1.5BL/s, a speed similar to that of migrating salmon and red and white muscles were sampled after each week. We quantified changes in key enzymes in aerobic and carbohydrate metabolism (citrate synthase (CS, β-hydroxyacyl-CoA dehydrogenase (HOAD, hexokinase (HK and changes in mRNA expression of major regulators of metabolic phenotype (AMPK, PPARs and lipid (carnitine palmitoyltransferase, CPT I, protein (aspartate aminotransferase, AST and carbohydrate (HK oxidation pathways. After one week of swimming substantial increases were seen in AMPK and PPARα mRNA expression and of their downstream target genes, CPTI and HK in red muscle. However, significant changes in CS and HK activity occurred only after 4 weeks. In contrast, there were few changes in mRNA expression and enzyme activities in white muscle over the 4-weeks. Red muscle results mimic those found in migrating salmon suggesting a strong influence of exercise on red muscle phenotype. In white muscle, only changes in AMPK and PPAR expression were similar to that seen with migrating salmon. However, in contrast to exercise alone, in natural migration HK decreased while AST increased suggesting that white muscle plays a role in supplying fuel and intermediates possibly through tissue breakdown during prolonged fasting. Dissecting individual and potentially synergistic effects of multiple stressors will enable us to determine major drivers of the metabolic phenotype and their impacts on whole animal

  14. Cytoskeletal Expression and Remodeling in Pluripotent Stem Cells. (United States)

    Boraas, Liana C; Guidry, Julia B; Pineda, Emma T; Ahsan, Tabassum


    Many emerging cell-based therapies are based on pluripotent stem cells, though complete understanding of the properties of these cells is lacking. In these cells, much is still unknown about the cytoskeletal network, which governs the mechanoresponse. The objective of this study was to determine the cytoskeletal state in undifferentiated pluripotent stem cells and remodeling with differentiation. Mouse embryonic stem cells (ESCs) and reprogrammed induced pluripotent stem cells (iPSCs), as well as the original un-reprogrammed embryonic fibroblasts (MEFs), were evaluated for expression of cytoskeletal markers. We found that pluripotent stem cells overall have a less developed cytoskeleton compared to fibroblasts. Gene and protein expression of smooth muscle cell actin, vimentin, lamin A, and nestin were markedly lower for ESCs than MEFs. Whereas, iPSC samples were heterogeneous with most cells expressing patterns of cytoskeletal proteins similar to ESCs with a small subpopulation similar to MEFs. This indicates that dedifferentiation during reprogramming is associated with cytoskeletal remodeling to a less developed state. In differentiation studies, it was found that shear stress-mediated differentiation resulted in an increase in expression of cytoskeletal intermediate filaments in ESCs, but not in iPSC samples. In the embryoid body model of spontaneous differentiation of pluripotent stem cells, however, both ESCs and iPSCs had similar gene expression for cytoskeletal proteins during early differentiation. With further differentiation, however, gene levels were significantly higher for iPSCs compared to ESCs. These results indicate that reprogrammed iPSCs more readily reacquire cytoskeletal proteins compared to the ESCs that need to form the network de novo. The strategic selection of the parental phenotype is thus critical not only in the context of reprogramming but also the ultimate functionality of the iPSC-differentiated cell population. Overall, this


    Directory of Open Access Journals (Sweden)

    E. D. Golovanova


    Full Text Available Aim. To study the effect of the long-term antihypertensive monotherapy with indapamide (Arifon Retard, 1,5 mg/d, metoprolol tartrate (Egilok Retard, 50 mg/d and combined therapy with indapamide and perindopril (Noliprel Forte, 1 tab/d: perindopril 4 mg and indapamide 1,25 mg on pulse wave velocity (PWV, cardio-ankle vascular index (CAVI and the sympathetic system activity.Material and methods. 88 patients, aged 30-59 y.o. (32 normotensive patients, 56 with arterial hypertension [HT] of 1-2 grades were examined. Biological age (BA was determined by the linear regression and the vascular wall age (VWA was estimated with the use of volume sphygmography (“VaSera-1000”, “Fucuda Denshi”, Japan. 39 patients with HT were randomized into 3 parallel groups with studied therapies lasted for 6 months. PWV, CAVI of the vessels of elastic, muscular and mixed types, blood pressure, measured in upper and lower extremities and heart rate variability (HRV were determined before and at the end of the therapies.Results. BA and VWA were elevated in all of patients with HT as compared with normotensive patients. The reduction in PWV and CAVI of the vessels of elastic and mixed types, HRV increase were found in patients with Arifon Retard monotherapy. Monotherapy with metoprolol significantly improved HVR without any influence on the vascular remodeling. Noliprel Forte significantly decreased in blood pressure in the upper and lower extremities, PWV and CAVI of the vessels of all types, decreased in VWA and increased in parasympathetic drive.Conclusion. Long-term therapy with Arifon Retard and Noliprel Forte resulted in decrease in vascular remodeling and increase in HRV simultaneously with significant antihypertensive effect in patients with HT. Metoprolol low doses therapy resulted in normalization of autonomic drive independently on antihypertensive action.

  16. Erythrocyte Stiffness during Morphological Remodeling Induced by Carbon Ion Radiation (United States)

    Zhang, Baoping; Liu, Bin; Zhang, Hong; Wang, Jizeng


    The adverse effect induced by carbon ion radiation (CIR) is still an unavoidable hazard to the treatment object. Thus, evaluation of its adverse effects on the body is a critical problem with respect to radiation therapy. We aimed to investigate the change between the configuration and mechanical properties of erythrocytes induced by radiation and found differences in both the configuration and the mechanical properties with involving in morphological remodeling process. Syrian hamsters were subjected to whole-body irradiation with carbon ion beams (1, 2, 4, and 6 Gy) or X-rays (2, 4, 6, and 12 Gy) for 3, 14 and 28 days. Erythrocytes in peripheral blood and bone marrow were collected for cytomorphological analysis. The mechanical properties of the erythrocytes were determined using atomic force microscopy, and the expression of the cytoskeletal protein spectrin-α1 was analyzed via western blotting. The results showed that dynamic changes were evident in erythrocytes exposed to different doses of carbon ion beams compared with X-rays and the control (0 Gy). The magnitude of impairment of the cell number and cellular morphology manifested the subtle variation according to the irradiation dose. In particular, the differences in the size, shape and mechanical properties of the erythrocytes were well exhibited. Furthermore, immunoblot data showed that the expression of the cytoskeletal protein spectrin-α1 was changed after irradiation, and there was a common pattern among its substantive characteristics in the irradiated group. Based on these findings, the present study concluded that CIR could induce a change in mechanical properties during morphological remodeling of erythrocytes. According to the unique characteristics of the biomechanical categories, we deduce that changes in cytomorphology and mechanical properties can be measured to evaluate the adverse effects generated by tumor radiotherapy. Additionally, for the first time, the current study provides a new

  17. Structural basis for recognition and remodeling of the TBP:DNA:NC2 complex by Mot1

    NARCIS (Netherlands)

    Butryn, Agata; Schuller, Jan M; Stoehr, Gabriele; Runge-Wollmann, Petra; Förster, Friedrich; Auble, David T; Hopfner, Karl-Peter


    Swi2/Snf2 ATPases remodel substrates such as nucleosomes and transcription complexes to control a wide range of DNA-associated processes, but detailed structural information on the ATP-dependent remodeling reactions is largely absent. The single subunit remodeler Mot1 (modifier of transcription 1)

  18. Malunion of distal radius fractures in children Remodeling speed in 33 children with angular malunions of >= 15 degrees

    NARCIS (Netherlands)

    Jeroense, K.T.V.; America, T.; Witbreuk, M.M.E.H.; van der Sluijs, J.A.


    Background and purpose - Distal forearm fractures in children have excellent remodeling potential. The current literature states that 15° is the maximum acceptable angulation limit, though studies focusing on remodeling capacity above this value are lacking. We present data on the remodeling process

  19. L-carnitine attenuates cardiac remodelling rather than vascular remodelling in deoxycorticosterone acetate-salt hypertensive rats. (United States)

    O'Brien, Daniel; Chunduri, Prasad; Iyer, Abishek; Brown, Lindsay


    L-carnitine is an important co-factor in fatty acid metabolism by mitochondria. This study has determined whether oral administration of L-carnitine prevents remodelling and the development of impaired cardiovascular function in deoxycorticosterone acetate (DOCA)-salt hypertensive rats (n = 6-12; #p carnitine (1.2% in food; 0.9 mg/g/day in DOCA-salt rats) decreased blood pressure (DOCA-salt 169 +/- 2; + L-carnitine 148 +/- 6# mmHg), decreased left ventricular wet weights (DOCA-salt 3.02 +/- 0.07; + L-carnitine 2.72 +/- 0.06# mg/g body-wt), decreased inflammatory cells in the replacement fibrotic areas, reduced left ventricular interstitial collagen content (DOCA-salt 14.4 +/- 0.2; + L-carnitine 8.7 +/- 0.5# % area), reduced diastolic stiffness constant (DOCA-salt 26.9 +/- 0.5; + L-carnitine 23.8 +/- 0.5# dimensionless) and decreased plasma malondialdehyde concentrations (DOCA-salt 26.9 +/- 0.8; + L-carnitine 21.2 +/- 0.4# micromol/l) without preventing endothelial dysfunction. L-carnitine attenuated the cardiac remodelling and improved cardiac function in DOCA-salt hypertension but produced minimal changes in aortic wall thickness and vascular function. This study suggests that the mitochondrial respiratory chain is a significant source of reactive oxygen species in the heart but less so in the vasculature in DOCA-salt rats, underlying the relatively selective cardiac responses to L-carnitine treatment.

  20. Mutation of neuron-specific chromatin remodeling subunit BAF53b: rescue of plasticity and memory by manipulating actin remodeling. (United States)

    Vogel Ciernia, Annie; Kramár, Enikö A; Matheos, Dina P; Havekes, Robbert; Hemstedt, Thekla J; Magnan, Christophe N; Sakata, Keith; Tran, Ashley; Azzawi, Soraya; Lopez, Alberto; Dang, Richard; Wang, Weisheng; Trieu, Brian; Tong, Joyce; Barrett, Ruth M; Post, Rebecca J; Baldi, Pierre; Abel, Ted; Lynch, Gary; Wood, Marcelo A


    Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons. We generated transgenic mice lacking subdomain 2 of Baf53b (BAF53bΔSB2). Long-term synaptic potentiation (LTP) and long-term memory, both of which are associated with phosphorylation of the actin severing protein cofilin, were assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically delivered into the hippocampus of BAF53bΔSB2 mice in an effort to rescue LTP and memory. BAF53bΔSB2 mutant mice show impairments in phosphorylation of synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory deficits are rescued by overexpression of a phosphorylation mimetic of cofilin. Baseline physiology and behavior were not affected by the mutation or the experimental treatment. This study suggests a potential link between nBAF function, actin cytoskeletal remodeling at the dendritic spine, and memory formation. This work shows that a targeted manipulation of synaptic function can rescue adult plasticity and memory deficits caused by manipulations of nBAF, and thereby provides potential novel avenues for therapeutic development for multiple intellectual disability disorders. © 2017 Vogel Ciernia et al.; Published by Cold Spring Harbor Laboratory Press.

  1. Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices.

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    Tjitske A Oenema

    Full Text Available Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A or TGF-β receptor kinase (SB431542 prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.

  2. Early ventricular restraint after myocardial infarction: extent of the wrap determines the outcome of remodeling. (United States)

    Enomoto, Yoshiharu; Gorman, Joseph H; Moainie, Sina L; Jackson, Benjamin M; Parish, Landi M; Plappert, Theodore; Zeeshan, Ahmad; St John-Sutton, Martin G; Gorman, Robert C


    Early infarct expansion initiates adverse remodeling, leads to left ventricular dilatation and portends a poor long-term outcome. Early mechanical prevention of infarct expansion has been proposed as a method to improve remodeling, but the extent of ventricular restraint necessary to optimize the salutary effect is not known. We tested the hypothesis that left ventricular restraint (wrap) is superior to infarct stiffening (patch). Infarction of 20% to 25% of the left ventricle was induced by coronary ligation in 69 sheep. Infarcts were either anteroapical (n = 33) or posterobasal (n = 36). Animals with each infarct received either no treatment (anteroapical, n = 26; posterobasal, n = 17), infarct stiffening with a localized Marlex mesh patch (posterobasal, n = 9) or left ventricular wrapping with Merseline mesh (anteroapical, n = 7; posterobasal, n = 10). End-systolic volume, end-diastolic volume, end-systolic muscle to cavity area ratio, left ventricular sphericity, ejection fraction, and degree of mitral regurgitation as determined by quantitative echocardiography were assessed before infarction and at 2, 5, and 8 weeks after infarction to evaluate the extent of left ventricular remodeling. Control animals in both groups experienced adverse remodeling. Anteroapical infarct animals developed large left ventricular aneurysms and the posterobasal infarct animals developed severe mitral regurgitation. Early infarct stiffening did not significantly improve any aspect of remodeling due to the posterobasal infarct. Early left ventricular wrapping significantly improved remodeling after both types of infarctions. Early left ventricular wrapping attenuates infarct expansion and has a salutary effect on remodeling. Simple infarct stiffening alone is not effective.

  3. Integrated remodeling-to-fracture finite element model of human proximal femur behavior. (United States)

    Hambli, Ridha; Lespessailles, Eric; Benhamou, Claude-Laurent


    The purpose of this work was to develop an integrated remodeling-to-fracture finite element model allowing for the combined simulation of (i) simulation of a human proximal femur remodeling under a given boundary conditions, (ii) followed by the simulation of its fracture behavior (force-displacement curve and fracture pattern) under quasi-static load. The combination of remodeling and fracture simulation into one unified model consists in considering that the femur properties resulting from the remodeling simulation correspond to the initial state for the fracture prediction. The remodeling model is based on phenomenological one based on a coupled strain and fatigue damage stimulus. The fracture model is based on continuum damage mechanics in order to predict the progressive fracturing process which allows to predict the fracture pattern and the complete force-displacement curve under quasi-static load. To prevent mesh-dependence that generally affects the damage propagation rate, regularization technique was applied in the current work. To investigate the potential of the proposed unified remodeling-to-fracture model, we performed remodeling simulations on a 3D proximal femur model for a duration of 365 days under five different daily loading conditions followed by a side fall fracture simulation reproducing previously published experimental tests (de Bakker et al. (2009), case C, male, 72 years old). We show here that the implementation of an integrated remodeling-to-fracture model provides more realistic prediction strategy to assess the bone remodeling effects on the fracture risk of bone. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

    Energy Technology Data Exchange (ETDEWEB)

    Ostrup, Olga, E-mail: [Institute of Basic Animal and Veterinary Sciences, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C (Denmark); Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo (Norway); Norwegian Center for Stem Cell Research, Oslo (Norway); Hyttel, Poul; Klaerke, Dan A. [Institute of Basic Animal and Veterinary Sciences, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C (Denmark); Collas, Philippe, E-mail: [Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo (Norway); Norwegian Center for Stem Cell Research, Oslo (Norway)


    Highlights: {yields} Xenopus egg extract remodels nuclei and alter cell growth characteristics. {yields} Ribosomal genes are reprogrammed within 6 h after extract exposure. {yields} rDNA reprogramming involves promoter targeting of SNF2H remodeling complex. {yields} Xenopus egg extract does not initiate stress-related response in somatic cells. {yields} Aza-cytidine elicits a stress-induced response in reprogrammed cells. -- Abstract: Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression. This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract and elicits a stress-type nuclear response. Thus, an early event of Xenopus egg extract-mediated nuclear reprogramming is the remodeling of ribosomal genes involving nucleolar remodeling complex. Condition-specific and rapid silencing of ribosomal genes may serve as a sensitive marker for evaluation of various reprogramming methods.

  5. Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Fu [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Chambon, Pierre [Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS UMR7104, INSERM U596, ULP, Collége de France) and Institut Clinique de la Souris, ILLKIRCH, Strasbourg (France); Tellides, George [Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT (United States); Kong, Wei [Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing (China); Zhang, Xiaoming, E-mail: [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Li, Wei [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China)


    Highlights: • TGF-β signaling in SMC contributes to the flow-induced vascular remodeling. • Disruption of TGF-β signaling in SMC can prevent this process. • Targeting SM-specific Tgfbr2 could be a novel therapeutic strategy for vascular remodeling. - Abstract: Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2{sup f/f}) and their corresponding wild-type background mice (MyhCre.Tgfbr2{sup WT/WT}) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process.

  6. Investigating the effect of remodelling signal type on the finite element based predictions of bone remodelling around the thrust plate prosthesis: a patient-specific comparison. (United States)

    Schmitz, M J; Clift, S E; Taylor, W R; Hertig, D; Warner, M D; Ploeg, H L; Bereiter, H


    The resorption of bone in the human femur following total hip arthroplasty is recognized to be related to the loading in the bone surrounding the prosthesis. However, the precise nature of the mechanical signal that influences the biological remodelling activity of the bone is not completely understood. In this study, a validated finite element modelling methodology was combined with a numerical algorithm to simulate the biological changes over time. This was used to produce bone remodelling predictions for an implanted thrust plate prosthesis (Centerpulse Orthopedics Limited) in a patient specific bone model. The analysis was then repeated using different mechanical signals to drive the remodelling algorithm. The results of these simulations were then compared to the patient-specific clinical data, to distinguish which of the candidate signals produced predictions consistent with the clinical evidence. Good agreement was found for a range of strain energy based signals and also deviatoric remodelling signals. The results, however, did not support the use of compressive dilatational strain as a candidate remodelling signal.

  7. Can experimental data in humans verify the finite element-based bone remodeling algorithm?

    DEFF Research Database (Denmark)

    Wong, C.; Gehrchen, P.M.; Kiaer, T.


    : The validity of 2 bone remodeling algorithms was evaluated by comparing against prospective bone mineral content measurements. Also, the potential stress shielding effect was examined using the 2 bone remodeling algorithms and the experimental bone mineral data. SUMMARY OF BACKGROUND DATA: In previous studies...... operated on with pedicle screws between L4 and L5. The stress shielding effect was also examined. The bone remodeling results were compared with prospective bone mineral content measurements of 4 patients. They were measured after surgery, 3-, 6- and 12-months postoperatively. RESULTS: After 1 year...

  8. Dysregulation of chromatin remodelling complexes in amyotrophic lateral sclerosis. (United States)

    Tibshirani, Michael; Zhao, Beibei; Gentil, Benoit J; Minotti, Sandra; Marques, Christine; Keith, Julia; Rogaeva, Ekaterina; Zinman, Lorne; Rouaux, Caroline; Robertson, Janice; Durham, Heather D


    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with paralysis resulting from dysfunction and loss of motor neurons. A common neuropathological finding is attrition of motor neuron dendrites, which make central connections vital to motor control. The chromatin remodelling complex, neuronal Brahma-related gene 1 (Brg1)-associated factor complex (nBAF), is critical for neuronal differentiation, dendritic extension and synaptic function. We have identified loss of the crucial nBAF subunits Brg1, Brg1-associated factor 53b and calcium responsive transactivator in cultured motor neurons expressing FUS or TAR-DNA Binding Protein 43 (TDP-43) mutants linked to familial ALS. When plasmids encoding wild-type or mutant human FUS or TDP-43 were expressed in motor neurons of dissociated spinal cord cultures prepared from E13 mice, mutant proteins in particular accumulated in the cytoplasm. Immunolabelling of nBAF subunits was reduced in proportion to loss of nuclear FUS or TDP-43 and depletion of Brg1 was associated with nuclear retention of Brg1 mRNA. Dendritic attrition (loss of intermediate and terminal dendritic branches) occurred in motor neurons expressing mutant, but not wild-type, FUS or TDP-43. This attrition was delayed by ectopic over-expression of Brg1 and was reproduced by inhibiting Brg1 activity either through genetic manipulation or treatment with the chemical inhibitor, (E)-1-(2-Hydroxyphenyl)-3-((1R, 4R)-5-(pyridin-2-yl)-2, 5-diazabicyclo[2.2.1]heptan-2-yl)prop-2-en-1-one, demonstrating the importance of Brg1 to maintenance of dendritic architecture. Loss of nBAF subunits was also documented in spinal motor neurons in autopsy tissue from familial amyotrophic sclerosis (chromosome 9 open reading frame 72 with G4C2 nucleotide expansion) and from sporadic cases with no identified mutation, pointing to dysfunction of nBAF chromatin remodelling in multiple forms of ALS. © The Author 2017. Published by Oxford University Press. All rights reserved

  9. Remodeling of Tumor Stroma and Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Anna; Ganss, Ruth, E-mail: [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)


    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

  10. Insights into innate immune signalling in controlling cardiac remodelling. (United States)

    Zhang, Yaxing; Huang, Zan; Li, Hongliang


    Canonical innate immune signalling involves complex cascades: multiple germline-encoded pattern recognition receptors rapidly recognize pathogen-associated or damage-associated molecular patterns to induce the production of cytokines, which bind to their corresponding receptors to orchestrate subsequent host defense phases. Inflammation is a healthy response to pathogenic signals, which are typically rapid and specific, and they terminate once the threat has passed. However, excessive activation or suppression of innate immune or inflammatory responses can lead to considerable human suffering, such as cardiac remodelling. Interestingly, recent studies have revealed that innate immune molecules in the parenchymal cells of the heart influence cardiac homeostasis not only by directly regulating innate immune responses but also through reprogrammed signalling pathways, which are independent of conventional innate immune signalling. Elucidating 'innate immune signalling reprogramming' events will help us better understand the functions of innate immune molecules and, moreover, the pathogenesis of cardiac diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email:

  11. Remodeling Intestinal Flora with Sleeve Gastrectomy in Diabetic Rats (United States)

    Huang, Xiaofei; Weng, Pan; Zhang, Huixin; Lu, Yingli


    Objective. As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. Methods. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals' weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis. Results. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy. Conclusion. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism. PMID:25165722

  12. The Circadian NAD+ Metabolism: Impact on Chromatin Remodeling and Aging

    Directory of Open Access Journals (Sweden)

    Yasukazu Nakahata


    Full Text Available Gene expression is known to be a stochastic phenomenon. The stochastic gene expression rate is thought to be altered by topological change of chromosome and/or by chromatin modifications such as acetylation and methylation. Changes in mechanical properties of chromosome/chromatin by soluble factors, mechanical stresses from the environment, or metabolites determine cell fate, regulate cellular functions, or maintain cellular homeostasis. Circadian clock, which drives the expression of thousands of genes with 24-hour rhythmicity, has been known to be indispensable for maintaining cellular functions/homeostasis. During the last decade, it has been demonstrated that chromatin also undergoes modifications with 24-hour rhythmicity and facilitates the fine-tuning of circadian gene expression patterns. In this review, we cover data which suggests that chromatin structure changes in a circadian manner and that NAD+ is the key metabolite for circadian chromatin remodeling. Furthermore, we discuss the relationship among circadian clock, NAD+ metabolism, and aging/age-related diseases. In addition, the interventions of NAD+ metabolism for the prevention and treatment of aging and age-related diseases are also discussed.

  13. Tissue design: how Drosophila tumors remodel their neighborhood. (United States)

    Patel, Parthive H; Edgar, Bruce A


    Drosophila genetics has long been appreciated as a powerful approach for discovering the normal functions of genes that act as oncogenes and tumor suppressors in human cancer. Recent studies have also highlighted its advantages for deciphering how such genes function during tumorigenesis itself. Here we detail studies relating to how tumors, generated in developing organs and adult stem cell-based tissues, remodel the tissue landscape to their benefit. Like mammalian tumors, insect tumors can dissolve extracellular matrix, recruit blood cells, migrate and invade other tissues. While much is known about how mammalian fibroblasts, immune cells and vasculature promote late tumorigenesis, less is understood about the very earliest stages of tumor development in mammals. Because Drosophila has fewer mitotic cells and a simpler tissue architecture, it affords easy detection and analysis of early clonal tumor growth. Drosophila studies have revealed both cooperative and competitive interactions between tumor and normal cells during early tumor growth. During development, these interactions typically occur with other proliferative progenitor cells, but in adult stem cell-based tissues, the stem cell niche can fuel tumor growth. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. [Pulmonary vascular remodeling in congenital cardiovascular abnormalities: an eternal topic]. (United States)

    Liu, Han-Min


    Pulmonary arterial hypertension (PAH) is one of the most severe complications of congenital heart defects with left to right shunt. Pulmonary vascular remodeling (PVR) is extremely essential in PAH. Therefore, prevention and reversion of PVR is one of the most important factors for improving quality of life for children suffering from PAH. In this article we reviewed the emerging research views on PVR from the disciplines of oncology and anti-tumor pharmacy. Two main sections were included. On the one hand, we introduced the "ATM signal turning point hypothesis" from the DNA damage response (DDR) mechanism research in oncology. The hypothesis suggests that the tumor-like proliferation of vascular smooth muscle cells might be the pathological basis of obstructive PAH. On the other hand, a new lung-targeted drug delivery system based on the fact that low concentration of anti-tumor drugs can inhibit angiogenesis without cellular toxicity was introduced. These new research directions could extend current practice in PVR therapy.

  15. Cardiac remodeling and myocardial dysfunction in obese spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Linz Dominik


    Full Text Available Abstract Background The additive effects of obesity and metabolic syndrome on left ventricular (LV maladaptive remodeling and function in hypertension are not characterized. Methods We compared an obese spontaneously hypertensive rat model (SHR-ob with lean spontaneously hypertensive rats (SHR-lean and normotensive controls (Ctr. LV-function was investigated by cardiac magnetic resonance imaging and invasive LV-pressure measurements. LV-interstitial fibrosis was quantified and protein levels of phospholamban (PLB, Serca2a and glucose transporters (GLUT1 and GLUT4 were determined by immunohistochemistry. Results Systolic blood pressure was similar in SHR-lean and SHR-ob (252 ± 7 vs. 242 ± 7 mmHg, p = 0.398 but was higher when compared to Ctr (155 ± 2 mmHg, p  Conclusion In addition to hypertension alone, metabolic syndrome and obesity adds to the myocardial phenotype by aggravating diastolic dysfunction and a progression towards systolic dysfunction. SHR-ob may be a useful model to develop new interventional and pharmacological treatment strategies for hypertensive heart disease and metabolic disorders.

  16. Footprint traversal by adenosine-triphosphate-dependent chromatin remodeler motor (United States)

    Garai, Ashok; Mani, Jesrael; Chowdhury, Debashish


    Adenosine-triphosphate (ATP)-dependent chromatin remodeling enzymes (CREs) are biomolecular motors in eukaryotic cells. These are driven by a chemical fuel, namely, ATP. CREs actively participate in many cellular processes that require accessibility of specific segments of DNA which are packaged as chromatin. The basic unit of chromatin is a nucleosome where 146 bp ˜ 50 nm of a double-stranded DNA (dsDNA) is wrapped around a spool formed by histone proteins. The helical path of histone-DNA contact on a nucleosome is also called “footprint.” We investigate the mechanism of footprint traversal by a CRE that translocates along the dsDNA. Our two-state model of a CRE captures effectively two distinct chemical (or conformational) states in the mechanochemical cycle of each ATP-dependent CRE. We calculate the mean time of traversal. Our predictions on the ATP dependence of the mean traversal time can be tested by carrying out in vitro experiments on mononucleosomes.

  17. Circadian remodeling of neuronal circuits involved in rhythmic behavior.

    Directory of Open Access Journals (Sweden)

    María Paz Fernández


    Full Text Available Clock output pathways are central to convey timing information from the circadian clock to a diversity of physiological systems, ranging from cell-autonomous processes to behavior. While the molecular mechanisms that generate and sustain rhythmicity at the cellular level are well understood, it is unclear how this information is further structured to control specific behavioral outputs. Rhythmic release of pigment dispersing factor (PDF has been proposed to propagate the time of day information from core pacemaker cells to downstream targets underlying rhythmic locomotor activity. Indeed, such circadian changes in PDF intensity represent the only known mechanism through which the PDF circuit could communicate with its output. Here we describe a novel circadian phenomenon involving extensive remodeling in the axonal terminals of the PDF circuit, which display higher complexity during the day and significantly lower complexity at nighttime, both under daily cycles and constant conditions. In support to its circadian nature, cycling is lost in bona fide clockless mutants. We propose this clock-controlled structural plasticity as a candidate mechanism contributing to the transmission of the information downstream of pacemaker cells.

  18. TGF-β Signaling in Bone Remodeling and Osteosarcoma Progression

    Directory of Open Access Journals (Sweden)

    Audrey Lamora


    Full Text Available Osteosarcomas are the most prevalent malignant primary bone tumors in children. Despite intensive efforts to improve both chemotherapeutics and surgical management, 40% of all osteosarcoma patients succumb to the disease. Specifically, the clinical outcome for metastatic osteosarcoma remains poor; less than 30% of patients who present metastases will survive five years after initial diagnosis. Treating metastatic osteosarcoma thus remains a challenge. One of the main characteristics of osteosarcomas is their ability to deregulate bone remodelling. The invasion of bone tissue by tumor cells indeed affects the balance between bone resorption and bone formation. This deregulation induces the release of cytokines or growth factors initially trapped in the bone matrix, such as transforming growth factor-β (TGF-β, which in turn promote tumor progression. Over the past years, there has been considerable interest in the TGF-β pathway within the cancer research community. This review discusses the involvement of the TGF-β signalling pathway in osteosarcoma development and in their metastatic progression.

  19. Inflammation and atrial remodeling after a mountain marathon. (United States)

    Wilhelm, M; Zueger, T; De Marchi, S; Rimoldi, S F; Brugger, N; Steiner, R; Stettler, C; Nuoffer, J-M; Seiler, C; Ith, M


    Endurance athletes have an increased risk of atrial fibrillation. We performed a longitudinal study on elite runners of the 2010 Jungfrau Marathon, a Swiss mountain marathon, to determine acute effects of long-distance running on the atrial myocardium. Ten healthy male athletes were included and examined 9 to 1 week prior to the race, immediately after, and 1, 5, and 8 days after the race. Mean age was 34.9 ± 4.2 years, and maximum oxygen consumption was 66.8 ± 5.8 mL/kg*min. Mean race time was 243.9 ± 17.7 min. Electrocardiographic-determined signal-averaged P-wave duration (SAPWD) increased significantly after the race and returned to baseline levels during follow-up (128.7 ± 10.9 vs. 137.6 ± 9.8 vs. 131.5 ± 8.6 ms; P marathon running was associated with a transient conduction delay in the atria, acute inflammation and increased atrial wall tension. This may reflect exercise-induced atrial myocardial edema and may contribute to atrial remodeling over time, generating a substrate for atrial arrhythmias. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Splenectomy Is Modifying the Vascular Remodeling of Thrombosis (United States)

    Frey, Maria K.; Alias, Sherin; Winter, Max P.; Redwan, Bassam; Stübiger, Gerald; Panzenboeck, Adelheid; Alimohammadi, Arman; Bonderman, Diana; Jakowitsch, Johannes; Bergmeister, Helga; Bochkov, Valery; Preissner, Klaus T.; Lang, Irene M.


    Background Splenectomy is a clinical risk factor for complicated thrombosis. We hypothesized that the loss of the mechanical filtering function of the spleen may enrich for thrombogenic phospholipids in the circulation, thereby affecting the vascular remodeling of thrombosis. Methods and Results We investigated the effects of splenectomy both in chronic thromboembolic pulmonary hypertension (CTEPH), a human model disease for thrombus nonresolution, and in a mouse model of stagnant flow venous thrombosis mimicking deep vein thrombosis. Surgically excised thrombi from rare cases of CTEPH patients who had undergone previous splenectomy were enriched for anionic phospholipids like phosphatidylserine. Similar to human thrombi, phosphatidylserine accumulated in thrombi after splenectomy in the mouse model. A postsplenectomy state was associated with larger and more persistent thrombi. Higher counts of procoagulant platelet microparticles and increased leukocyte–platelet aggregates were observed in mice after splenectomy. Histological inspection revealed a decreased number of thrombus vessels. Phosphatidylserine‐enriched phospholipids specifically inhibited endothelial proliferation and sprouting. Conclusions After splenectomy, an increase in circulating microparticles and negatively charged phospholipids is enhanced by experimental thrombus induction. The initial increase in thrombus volume after splenectomy is due to platelet activation, and the subsequent delay of thrombus resolution is due to inhibition of thrombus angiogenesis. The data illustrate a potential mechanism of disease in CTEPH. PMID:24584745

  1. Aberrant Pulmonary Vascular Growth and Remodeling in Bronchopulmonary Dysplasia (United States)

    Alvira, Cristina M.


    In contrast to many other organs, a significant portion of lung development occurs after birth during alveolarization, thus rendering the lung highly susceptible to injuries that may disrupt this developmental process. Premature birth heightens this susceptibility, with many premature infants developing the chronic lung disease, bronchopulmonary dysplasia (BPD), a disease characterized by arrested alveolarization. Over the past decade, tremendous progress has been made in the elucidation of mechanisms that promote postnatal lung development, including extensive data suggesting that impaired pulmonary angiogenesis contributes to the pathogenesis of BPD. Moreover, in addition to impaired vascular growth, patients with BPD also frequently demonstrate alterations in pulmonary vascular remodeling and tone, increasing the risk for persistent hypoxemia and the development of pulmonary hypertension. In this review, an overview of normal lung development will be presented, and the pathologic features of arrested development observed in BPD will be described, with a specific emphasis on the pulmonary vascular abnormalities. Key pathways that promote normal pulmonary vascular development will be reviewed, and the experimental and clinical evidence demonstrating alterations of these essential pathways in BPD summarized. PMID:27243014

  2. Fibroblast cytoskeletal remodeling induced by tissue stretch involves ATP signaling. (United States)

    Langevin, Helene M; Fujita, Takumi; Bouffard, Nicole A; Takano, Takahiro; Koptiuch, Cathryn; Badger, Gary J; Nedergaard, Maiken


    Fibroblasts in whole areolar connective tissue respond to static stretching of the tissue by expanding and remodeling their cytoskeleton within minutes both ex vivo and in vivo. This study tested the hypothesis that the mechanism of fibroblast expansion in response to tissue stretch involves extracellular ATP signaling. In response to tissue stretch ex vivo, ATP levels in the bath solution increased significantly, and this increase was sustained for 20 min, returning to baseline at 60 min. No increase in ATP was observed in tissue incubated without stretch or tissue stretched in the presence of the Rho kinase inhibitor Y27632. The increase in fibroblast cross sectional area in response to tissue stretch was blocked by both suramin (a purinergic receptor blocker) and apyrase (an enzyme that selectively degrades extracellular ATP). Furthermore, connexin channel blockers (octanol and carbenoxolone), but not VRAC (fluoxetine) or pannexin (probenecid) channel blockers, inhibited fibroblast expansion. Together, these results support a mechanism in which extracellular ATP signaling via connexin hemichannels mediate the active change in fibroblast shape that occurs in response to a static increase in tissue length. Copyright © 2013 Wiley Periodicals, Inc.

  3. Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials (United States)

    Liu, Jialing; Wang, Yongting; Akamatsu, Yosuke; Lee, Chih Cheng; Stetler, R Anne; Lawton, Michael T.; Yang, Guo-Yuan


    The brain vasculature has been increasingly recognized as a key player that directs brain development, regulates homeostasis, and contributes to pathological processes. Following ischemic stroke, the reduction of blood flow elicits a cascade of changes and leads to vascular remodeling. However, the temporal profile of vascular changes after stroke is not well understood. Growing evidence suggests that the early phase of cerebral blood volume (CBV) increase is likely due to the improvement in collateral flow, also known as arteriogenesis, whereas the late phase of CBV increase is attributed to the surge of angiogenesis. Arteriogenesis is triggered by shear fluid stress followed by activation of endothelium and inflammatory processes, while angiogenesis induces a number of pro-angiogenic factors and circulating endothelial progenitor cells (EPCs). The status of collaterals in acute stroke has been shown to have several prognostic implications, while the causal relationship between angiogenesis and improved functional recovery has yet to be established in patients. A number of interventions aimed at enhancing cerebral blood flow including increasing collateral recruitment are under clinical investigation. Transplantation of EPCs to improve angiogenesis is also underway. Knowledge in the underlying physiological mechanisms for improved arteriogenesis and angiogenesis shall lead to more effective therapies for ischemic stroke. PMID:24291532

  4. Modeling effects of axial extension on arterial growth and remodeling. (United States)

    Valentín, Arturo; Humphrey, Jay D


    Diverse mechanical perturbations elicit arterial growth and remodeling responses that appear to optimize structure and function so as to promote mechanical homeostasis. For example, it is well known that functional adaptations to sustained changes in transmural pressure and blood flow primarily affect wall thickness and caliber to restore circumferential and wall shear stresses toward normal. More recently, however, it has been shown that changes in axial extension similarly prompt dramatic cell and matrix reorganization and turnover, resulting in marked changes in unloaded geometry and mechanical behavior that presumably restore axial stress toward normal. Because of the inability to infer axial stress from in vivo measurements, simulations are needed to examine this hypothesis and to guide the design of future experiments. In this paper, we show that a constrained mixture model predicts salient features of observed responses to step increases in axial extension, including marked increases in fibrous constituent production, leading to a compensatory lengthening that restores original mechanical behavior. Because axial extension can be modified via diverse surgical procedures, including bypass operations, and exploited in tissue regeneration research, there is a need for increased attention to this important aspect of arterial biomechanics and mechanobiology.

  5. Apoptosis during embryonic tissue remodeling is accompanied by cell senescence (United States)

    Lorda-Diez, Carlos I.; Garcia-Riart, Beatriz; Montero, Juan A.; Rodriguez-León, Joaquín; Garcia-Porrero, Juan A; Hurle, Juan M.


    This study re-examined the dying process in the interdigital tissue during the formation of free digits in the developing limbs. We demonstrated that the interdigital dying process was associated with cell senescence, as deduced by induction of β-gal activity, mitotic arrest, and transcriptional up-regulation of p21 together with many components of the senescence-associated secretory phenotype. We also found overlapping domains of expression of members of the Btg/Tob gene family of antiproliferative factors in the regressing interdigits. Notably, Btg2 was up-regulated during interdigit remodeling in species with free digits but not in the webbed foot of the duck. We also demonstrate that oxidative stress promoted the expression of Btg2, and that FGF2 and IGF1 which are survival signals for embryonic limb mesenchyme inhibited Btg2 expression. Btg2 overexpression in vivo and in vitro induced all the observed changes during interdigit regression, including oxidative stress, arrest of cell cycle progression, transcriptional regulation of senescence markers, and caspase-mediated apoptosis. Consistent with the central role of p21 on cell senescence, the transcriptional effects induced by overexpression of Btg2 are attenuated by silencing p21. Our findings indicate that cell senescence and apoptosis are complementary processes in the regression of embryonic tissues and share common regulatory signals. PMID:26568417

  6. Porosity Defect Remodeling and Tensile Analysis of Cast Steel

    Directory of Open Access Journals (Sweden)

    Linfeng Sun


    Full Text Available Tensile properties on ASTM A216 WCB cast steel with centerline porosity defect were studied with radiographic mapping and finite element remodeling technique. Non-linear elastic and plastic behaviors dependent on porosity were mathematically described by relevant equation sets. According to the ASTM E8 tensile test standard, matrix and defect specimens were machined into two categories by two types of height. After applying radiographic inspection, defect morphologies were mapped to the mid-sections of the finite element models and the porosity fraction fields had been generated with interpolation method. ABAQUS input parameters were confirmed by trial simulations to the matrix specimen and comparison with experimental outcomes. Fine agreements of the result curves between simulations and experiments could be observed, and predicted positions of the tensile fracture were found to be in accordance with the tests. Chord modulus was used to obtain the equivalent elastic stiffness because of the non-linear features. The results showed that elongation was the most influenced term to the defect cast steel, compared with elastic stiffness and yield stress. Additional visual explanations on the tensile fracture caused by void propagation were also given by the result contours at different mechanical stages, including distributions of Mises stress and plastic strain.

  7. Remodeling intestinal flora with sleeve gastrectomy in diabetic rats. (United States)

    Huang, Xiaofei; Weng, Pan; Zhang, Huixin; Lu, Yingli


    As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals' weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism.

  8. Influence of ethnic background on left atrial markers of inflammation, endothelial function and tissue remodelling

    Directory of Open Access Journals (Sweden)

    Carlee D. Ruediger


    Conclusion: Caucasian and Indian populations demonstrate similar inflammatory, endothelial function or tissue remodelling profiles. This study suggests a lack of an impact of different ethnicity in these populations in terms of thrombogenic risk.

  9. Soy milk versus simvastatin for preventing atherosclerosis and left ventricle remodeling in LDL receptor knockout mice

    National Research Council Canada - National Science Library

    Santos, L; Davel, A.P; Almeida, T.I.R; Almeida, M.R; Soares, E.A; Fernandes, G.J.M; Magalhães, S.F; Barauna, V.G; Garcia, J.A.D


    .... In this study, we compared the effects of oral treatment with soy milk and simvastatin on dyslipidemia, left ventricle remodeling and atherosclerotic lesion of LDL receptor knockout mice (LDLr...

  10. Decreased coronary flow reserve in hypertrophic cardiomyopathy is related to remodeling of the coronary microcirculation

    NARCIS (Netherlands)

    M.J.M. Kofflard (Marcel); D.J.G.M. Duncker (Dirk); C. von Birgelen (Clemens); S.G. Carlier (Stephan); M. Kliffen (Mike); P.W.J.C. Serruys (Patrick); R. Krams (Rob); F.J. ten Cate (Folkert)


    textabstractBACKGROUND: Ischemia occurs frequently in hypertrophic cardiomyopathy (HCM) without evidence of epicardial stenosis. This study evaluates the hypothesis that the occurrence of ischemia in HCM is related to remodeling of the coronary microcirculation. METHODS AND

  11. Wave Propagation of Junctional Remodeling in Collective Cell Movement of Epithelial Tissue: Numerical Simulation Study

    Directory of Open Access Journals (Sweden)

    Tetsuya Hiraiwa


    Full Text Available During animal development, epithelial cells forming a monolayer sheet move collectively to achieve the morphogenesis of epithelial tissues. One driving mechanism of such collective cell movement is junctional remodeling, which is found in the process of clockwise rotation of Drosophila male terminalia during metamorphosis. However, it still remains unknown how the motions of cells are spatiotemporally organized for collective movement by this mechanism. Since these moving cells undergo elastic deformations, the influence of junctional remodeling may mechanically propagate among them, leading to spatiotemporal pattern formations. Here, using a numerical cellular vertex model, we found that the junctional remodeling in collective cell movement exhibits spatiotemporal self-organization without requiring spatial patterns of molecular signaling activity. The junctional remodeling propagates as a wave in a specific direction with a much faster speed than that of cell movement. Such propagation occurs in both the absence and presence of fluctuations in the contraction of cell boundaries.

  12. Tooth wear and dentoalveolar remodeling are key factors of morphological variation in the Dmanisi mandibles

    National Research Council Canada - National Science Library

    Ann Margvelashvili; Christoph P. E. Zollikofer; David Lordkipanidze; Timo Peltomäki; Marcia S. Ponce de León


    ...–gatherer populations. We identify a consistent pattern of mandibular morphological alteration, suggesting that dental wear and compensatory remodeling mechanisms remained fairly constant throughout the evolution of the genus Homo...

  13. Control of bone mass and remodeling by PTH receptor signaling in osteocytes.

    Directory of Open Access Journals (Sweden)

    Charles A O'Brien


    Full Text Available Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation. Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5 attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. These findings demonstrate that PTH receptor signaling in osteocytes increases bone mass and the rate of bone remodeling through LRP5-dependent and -independent mechanisms, respectively.

  14. Numerical simulation of the remodelling process of trabecular architecture around dental implants. (United States)

    Wang, Chao; Wang, Lizhen; Liu, Xiaoyu; Fan, Yubo


    Dental implants may alter the mechanical environment in the jawbone, thereby causing remodelling and adaptation of the surrounding trabecular bone tissues. To improve the efficacy of dental implant systems, it is necessary to consider the effect of bone remodelling on the performance of the prosthetic systems. In this study, finite element simulations were implemented to predict the evolution of microarchitecture around four implant systems using a previously developed model that combines both adaptive and microdamage-based mechano-sensory mechanisms in bone remodelling process. Changes in the trabecular architecture around dental implants were mainly focused. The simulation results indicate that the orientational and ladder-like architecture around the implants predicted herein is in good agreement with those observed in animal experiments and clinical observations. The proposed algorithms were shown to be effective in simulating the remodelling process of trabecular architecture around dental implant systems. In addition, the architectural features around four typical dental implant systems in alveolar bone were evaluated comparatively.

  15. The role of Hippo/yes-associated protein signalling in vascular remodelling associated with cardiovascular disease. (United States)

    He, Jinlong; Bao, Qiankun; Yan, Meng; Liang, Jing; Zhu, Yi; Wang, Chunjiong; Ai, Ding


    Vascular remodelling is a vital process of a wide range of cardiovascular diseases and represents the altered structure and arrangement of blood vessels. The Hippo pathway controls organ size by regulating cell survival, proliferation and apoptosis. Yes-associated protein (YAP), a transcription coactivator, is a downstream effector of the Hippo pathway. There is growing evidence for the importance of the Hippo/YAP pathway in vascular-remodelling and related cardiovascular diseases. The Hippo/YAP pathway alters extracellular matrix production or degradation and the growth, death and migration of vascular smooth muscle cells and endothelial cells, which contributes to vascular remodelling in cardiovascular diseases such as pulmonary hypertension, atherosclerosis, restenosis, aortic aneurysms and angiogenesis. In this review, we summarize and discuss recent findings about the roles and mechanisms of Hippo/YAP signalling in vascular remodelling and related conditions. © 2017 The British Pharmacological Society.

  16. Treprostinil in advanced experimental pulmonary hypertension : Beneficial outcome without reversed pulmonary vascular remodeling

    NARCIS (Netherlands)

    van Albada, Mirjam E.; van Veghel, Richard; Cromme-Dijkhuis, Adri H.; Schoemaker, Regien G.; Berger, Ro F. M. E.


    Introduction: Beneficial effects of treprostmil, a stable prostacyclin analogue, were demonstrated in patients with pulmonary arterial hypertension (PAH). Although regression of pulmonary vascular remodeling has been suggested as therapeutic mechanism, its mode of action remains unknown. Methods:

  17. Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling

    NARCIS (Netherlands)

    Everts, V.; van der Zee, E.; Creemers, L.; Beertsen, W.


    Collagens of most connective tissues are subject to continuous remodelling and turnover, a phenomenon which occurs under both physiological and pathological conditions. Degradation of these proteins involves participation of a variety of proteolytic enzymes including members of the following

  18. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben


    Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling....... Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...... transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed...

  19. Myocardial Infarction in a Young Female with Palindromic Rheumatism: A Consequence of Negative Remodeling

    Directory of Open Access Journals (Sweden)

    Timothy R. Larsen


    Full Text Available Palindromic rheumatism is a rare disease associated with systemic inflammation. Negative or constrictive coronary artery remodeling is typically not seen until the 7th or 8th decade of life. We report a case of a young female with palindromic rheumatism who suffered a non-ST segment elevation myocardial infarction secondary to a flow-limiting lesion that demonstrated negative remodeling by intravascular ultrasound (IVUS.

  20. Surgical treatment of ischemic mitral regurgitation might not influence ventricular remodeling. (United States)

    Enomoto, Yoshiharu; Gorman, Joseph H; Moainie, Sina L; Guy, T Sloane; Jackson, Benjamin M; Parish, Landi M; Plappert, Theodore; Zeeshan, Ahmad; St John-Sutton, Martin G; Gorman, Robert C


    Surgical treatment for ischemic mitral regurgitation has become more aggressive. However, no clinical study has demonstrated that surgical correction of chronic ischemic mitral regurgitation improves survival. We used 4 well-developed ovine models of postinfarction left ventricular remodeling to test the hypothesis that ischemic mitral regurgitation does not significantly contribute to postinfarction left ventricular remodeling. Infarction of 21% to 24% of the left ventricular mass was induced by means of coronary ligation in 77 sheep. Infarctions varied only by anatomic location in the left ventricle: anteroapical, n = 26; anterobasal, n = 16; laterobasal, n = 9; and posterobasal, n = 20. Six additional sheep had ring annuloplasty before posterobasal infarction. End-systolic and end-diastolic left ventricular volume, end-systolic muscle-to-cavity area ratio, left ventricular sphericity, ejection fraction, and degree of ischemic mitral regurgitation, as determined by means of quantitative echocardiography, were assessed before infarction and at 2, 5, and 8 weeks after infarction. All infarcts resulted in significant postinfarction remodeling and decreased ejection fraction. Anteroapical infarcts lead to left ventricular aneurysms. Only posterobasal infarcts caused severe and progressive ischemic mitral regurgitation. Remodeling because of posterobasal infarcts was not more severe than that caused by infarcts at other locations. Furthermore, prophylactic annuloplasty prevented the development of mitral regurgitation after posterobasal infarction but had no effect on remodeling. The extent of postinfarction remodeling is determined on the basis of infarct size and location. The development of ischemic mitral regurgitation might not contribute significantly to adverse remodeling. Ischemic mitral regurgitation is likely a manifestation rather than an important impetus for postinfarction remodeling.

  1. A remodelling metric for angular fibre distributions and its application to diseased carotid bifurcations.

    LENUS (Irish Health Repository)

    Creane, Arthur


    Many soft biological tissues contain collagen fibres, which act as major load bearing constituents. The orientation and the dispersion of these fibres influence the macroscopic mechanical properties of the tissue and are therefore of importance in several areas of research including constitutive model development, tissue engineering and mechanobiology. Qualitative comparisons between these fibre architectures can be made using vector plots of mean orientations and contour plots of fibre dispersion but quantitative comparison cannot be achieved using these methods. We propose a \\'remodelling metric\\' between two angular fibre distributions, which represents the mean rotational effort required to transform one into the other. It is an adaptation of the earth mover\\'s distance, a similarity measure between two histograms\\/signatures used in image analysis, which represents the minimal cost of transforming one distribution into the other by moving distribution mass around. In this paper, its utility is demonstrated by considering the change in fibre architecture during a period of plaque growth in finite element models of the carotid bifurcation. The fibre architecture is predicted using a strain-based remodelling algorithm. We investigate the remodelling metric\\'s potential as a clinical indicator of plaque vulnerability by comparing results between symptomatic and asymptomatic carotid bifurcations. Fibre remodelling was found to occur at regions of plaque burden. As plaque thickness increased, so did the remodelling metric. A measure of the total predicted fibre remodelling during plaque growth, TRM, was found to be higher in the symptomatic group than in the asymptomatic group. Furthermore, a measure of the total fibre remodelling per plaque size, TRM\\/TPB, was found to be significantly higher in the symptomatic vessels. The remodelling metric may prove to be a useful tool in other soft tissues and engineered scaffolds where fibre adaptation is also present.

  2. Effects of cigarette smoke and chronic hypoxia on airways remodeling and resistance. Clinical significance


    Olea, Elena; Prieto-Lloret, Jesús; Gonzalez-Martin, Carmen; Vega Agapito, Victoria; Gonzalez-Obeso, Elvira; Agapito, Teresa; Obeso, Ana; González, Constancio


    Previously we have reported that association of cigarette smoke (CS) and chronic hypoxia (CH) interact positively to physiopathologically remodel pulmonary circulation. In present study we have exposed guinea pigs to CS smoke (four cigarettes/day; 3 months; CS) and to chronic hypoxia (12% O2, 15 days; CH) alone or in combination (CSCH animals) and evaluated airways remodeling and resistance assessed as Penh (enhance pause). We measured Penh while animals breathe air, 10% O2 and 5% CO2 and fou...

  3. Broken silence restored-remodeling primes for deacetylation at replication forks

    DEFF Research Database (Denmark)

    Jasencakova, Zuzana; Groth, Anja


    Faithful propagation of chromatin structures requires assimilation of new histones to the modification profile of individual loci. In this issue of Molecular Cell, Rowbotham and colleagues identify a remodeler, SMARCAD1, acting at replication sites to facilitate histone deacetylation and restorat......Faithful propagation of chromatin structures requires assimilation of new histones to the modification profile of individual loci. In this issue of Molecular Cell, Rowbotham and colleagues identify a remodeler, SMARCAD1, acting at replication sites to facilitate histone deacetylation...

  4. Cardiac remodeling in preterm infants with prolonged exposure to a patent ductus arteriosus. (United States)

    de Waal, Koert; Phad, Nilkant; Collins, Nick; Boyle, Andrew


    Sustained volume load due to a patent ductus arteriosus (PDA) leads to cardiac remodeling. Remodeling changes can become pathological and are associated with cardiovascular disease progression. Data on remodeling changes in preterm infants is not available. Clinical and echocardiography data were collected in preterm infants 14 days) exposure to a PDA were compared to control infants without a PDA. Thirty out of 189 infants had prolonged exposure to a PDA. The left heart remodeled to a larger and more spherical shape and thus significantly increased in volume. Most changes occurred in the first 4 weeks, plateaued, and then returned to control values. Systolic function and estimates of filling pressure increased and effective arterial elastance reduced with a PDA, however contractility was unchanged. Wall thickness increased after 4 weeks of increased volume exposure. The preterm PDA induces early and significant remodeling of the left heart. A compensated cardiac physiology was seen with preserved systolic function, suggesting adaptive rather than pathological remodeling changes with prolonged exposure to a PDA. © 2017 Wiley Periodicals, Inc.

  5. Effect of nintedanib on airway inflammation and remodeling in a murine chronic asthma model. (United States)

    Lee, Hwa Young; Hur, Jung; Kim, In Kyoung; Kang, Ji Young; Yoon, Hyoung Kyu; Lee, Sook Young; Kwon, Soon Suk; Kim, Young Kyoon; Rhee, Chin Kook

    Nintedanib is a multi-tyrosine kinase receptor inhibitor recently approved for treatment of idiopathic pulmonary fibrosis. Although angiogenesis is a key process involved in airway structural changes in patients with bronchial asthma, the effect of nintedanib targeting the angiokinase pathway on airway inflammation and remodeling has not been evaluated. We used a 3-month ovalbumin (OVA) challenge mouse model of airway remodeling. Nintedanib was orally administrated during the challenge period, and the effects were examined based on the percentage of airway inflammatory cells, airway hyper-reactivity (AHR), peribronchial goblet cell hyperplasia, total lung collagen and smooth muscle area. The expression of growth factor receptors was analyzed in mice lung tissues. The OVA challenged group showed a significant increase in airway eosinophilic inflammation, elevated Th2 cytokines, AHR, and airway remodeling compared to those in the control group. The airway remodeling process, as evaluated by goblet cell hyperplasia, total lung collagen level, and airway smooth muscle area, was suppressed by nintedanib compared to that by OVA. Nintedanib effectively suppressed the phosphorylation of vascular endothelial growth factor/ platelet derived growth factor subunit2/fibroblast growth factor3 receptors in the mice lung. Nintedanib effectively ameliorated airway inflammation and remodeling in an OVA-induced chronic asthma model. These results suggest that nintedanib could be a new treatment agent targeting airway remodeling in patients with severe asthma.

  6. A 3-D constrained mixture model for mechanically mediated vascular growth and remodeling (United States)

    Wan, William; Hansen, Laura


    In contrast to the widely applied approach to model soft tissue remodeling employing the concept of volumetric growth, microstructurally motivated models are capable of capturing many of the underlying mechanisms of growth and remodeling; i.e., the production, removal, and remodeling of individual constituents at different rates and to different extents. A 3-dimensional constrained mixture computational framework has been developed for vascular growth and remodeling, considering new, microstructurally motivated kinematics and constitutive equations and new stress and muscle activation mediated evolution equations. Our computational results for alterations in flow and pressure, using reasonable physiological values for rates of constituent growth and turnover, concur with findings in the literature. For example, for flow-induced remodeling, our simulations predict that, although the wall shear stress is restored completely, the circumferential stress is not restored employing realistic physiological rate parameters. Also, our simulations predict different levels of thickening on inner versus outer wall locations, as shown in numerous reports of pressure-induced remodeling. Whereas the simulations are meant to be illustrative, they serve to highlight the experimental data currently lacking to fully quantify mechanically mediated adaptations in the vasculature. PMID:20039091

  7. Trabecular bone remodelling simulated by a stochastic exchange of discrete bone packets from the surface. (United States)

    Hartmann, M A; Dunlop, J W C; Bréchet, Y J M; Fratzl, P; Weinkamer, R


    Human bone is constantly renewed through life via the process of bone remodelling, in which individual packets of bone are removed by osteoclasts and replaced by osteoblasts. Remodelling is mechanically controlled, where osteocytes embedded within the bone matrix are thought to act as mechanical sensors. In this computational work, a stochastic model for bone remodelling is used in which the renewal of bone material occurs by exchange of discrete bone packets. We tested different hypotheses of how the mechanical stimulus for bone remodelling is integrated by osteocytes and sent to actor cells on the bone's surface. A collective (summed) signal from multiple osteocytes as opposed to an individual (maximal) signal from a single osteocyte was found to lead to lower inner porosity and surface roughness of the simulated bone structure. This observation can be interpreted in that collective osteocyte signalling provides an effective surface tension to the remodelling process. Furthermore, the material heterogeneity due to remodelling was studied on a network of trabeculae. As the model is discrete, the age of individual bone packets can be monitored with time. The simulation results were compared with experimental data coming from quantitative back scattered electron imaging by transforming the information about the age of the bone packet into a mineral content. Discrepancies with experiments indicate that osteoclasts preferentially resorb low mineralized, i.e. young, bone at the bone's surface. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Myocardial remodeling in diabetic cardiomyopathy associated with cardiac mast cell activation.

    Directory of Open Access Journals (Sweden)

    Zhi Gang Huang

    Full Text Available Diabetic cardiomyopathy is a specific disease process distinct from coronary artery disease and hypertension. The disease features cardiac remodeling stimulated by hyperglycemia of the left ventricle wall and disrupts contractile functions. Cardiac mast cells may be activated by metabolic byproducts resulted from hyperglycermia and then participate in the remodeling process by releasing a multitude of cytokines and bioactive enzymes. Nedocromil, a pharmacologic stabilizer of mast cells, has been shown to normalize cytokine levels and attenuate cardiac remodeling. In this study, we describe the activation of cardiac mast cells by inducing diabetes in normal mice using streptozotocin (STZ. Next, we treated the diabetic mice with nedocromil for 12 weeks and then examined their hearts for signs of cardiac remodeling and quantified contractile function. We observed significantly impaired heart function in diabetic mice, as well as increased cardiac mast cell density and elevated mast cell secretions that correlated with gene expression and aberrant cytokine levels associated with cardiac remodeling. Nedocromil treatment halted contractile dysfunction in diabetic mice and reduced cardiac mast cell density, which correlated with reduced bioactive enzyme secretions, reduced expression of extracellular matrix remodeling factors and collagen synthesis, and normalized cytokine levels. However, the results showed nedocromil treatments did not return diabetic mice to a normal state. We concluded that manipulation of cardiac mast cell function is sufficient to attenuate cardiomyopathy stimulated by diabetes, but other cellular pathways also contribute to the disease process.

  9. Regurgitation Hemodynamics Alone Cause Mitral Valve Remodeling Characteristic of Clinical Disease States In Vitro. (United States)

    Connell, Patrick S; Azimuddin, Anam F; Kim, Seulgi E; Ramirez, Fernando; Jackson, Matthew S; Little, Stephen H; Grande-Allen, K Jane


    Mitral valve regurgitation is a challenging clinical condition that is frequent, highly varied, and poorly understood. While the causes of mitral regurgitation are multifactorial, how the hemodynamics of regurgitation impact valve tissue remodeling is an understudied phenomenon. We employed a pseudo-physiological flow loop capable of long-term organ culture to investigate the early progression of remodeling in living mitral valves placed in conditions resembling mitral valve prolapse (MVP) and functional mitral regurgitation (FMR). Valve geometry was altered to mimic the hemodynamics of controls (no changes from native geometry), MVP (5 mm displacement of papillary muscles towards the annulus), and FMR (5 mm apical, 5 mm lateral papillary muscle displacement, 65% larger annular area). Flow measurements ensured moderate regurgitant fraction for regurgitation groups. After 1-week culture, valve tissues underwent mechanical and compositional analysis. MVP conditioned tissues were less stiff, weaker, and had elevated collagen III and glycosaminoglycans. FMR conditioned tissues were stiffer, more brittle, less extensible, and had more collagen synthesis, remodeling, and crosslinking related enzymes and proteoglycans, including decorin, matrix metalloproteinase-1, and lysyl oxidase. These models replicate clinical findings of MVP (myxomatous remodeling) and FMR (fibrotic remodeling), indicating that valve cells remodel extracellular matrix in response to altered mechanical homeostasis resulting from disease hemodynamics.

  10. Inhibition of nitric oxide synthases abrogates pregnancy-induced uterine vascular expansive remodeling. (United States)

    Osol, George; Barron, Carolyn; Gokina, Natalia; Mandala, Maurizio


    It was the aim of this study to test the hypothesis that hypertension and/or inhibition of nitric oxide (NO) synthases alters uterine vascular remodeling during pregnancy. Using a model of hypertension (NO synthase inhibition with L-NAME) in nonpregnant and pregnant rats, comparisons were made with age-matched controls, as well as with animals receiving hydralazine along with L-NAME to maintain normotension in the presence of NO synthase inhibition. Circumferential and axial remodeling of large (main uterine, MUA) and small (premyometrial radial) arteries were quantified and compared. L-NAME treatment prevented expansive circumferential remodeling of the MUA; cotreatment with hydralazine was without effect. Circumferential remodeling of smaller premyometrial radial arteries was also significantly attenuated in hypertensive pregnant animals, while premyometrial radial arteries from rats receiving hydralazine with L-NAME were of intermediate diameter. Neither hypertension nor NO synthase inhibition had any effect on the substantial (200-300%) axial growth of MUA or premyometrial radial arteries. NO plays a major role in facilitating pregnancy-induced expansive remodeling in the uterine circulation, particularly in larger arteries. Some beneficial effects of hydralazine on expansive circumferential remodeling were noted in smaller radial vessels, and these may be linked to its prevention of systemic hypertension and/or to local effects on the arterial wall. Neither NO synthase inhibition nor hypertension had any effect on arterial longitudinal growth.

  11. Sensory organ remodeling in Caenorhabditis elegans requires the zinc-finger protein ZTF-16. (United States)

    Procko, Carl; Lu, Yun; Shaham, Shai


    Neurons and glia display remarkable morphological plasticity, and remodeling of glia may facilitate neuronal shape changes. The molecular basis and control of glial shape changes is not well understood. In response to environmental stress, the nematode Caenorhabditis elegans enters an alternative developmental state, called dauer, in which glia and neurons of the amphid sensory organ remodel. Here, we describe a genetic screen aimed at identifying genes required for amphid glia remodeling. We previously demonstrated that remodeling requires the Otx-type transcription factor TTX-1 and its direct target, the receptor tyrosine kinase gene ver-1. We now find that the hunchback/Ikaros-like C2H2 zinc-finger factor ztf-16 is also required. We show that ztf-16 mutants exhibit pronounced remodeling defects, which are explained, at least in part, by defects in the expression of ver-1. Expression and cell-specific rescue studies suggest that ztf-16, like ttx-1, functions within glia; however, promoter deletion studies show that ztf-16 acts through a site on the ver-1 promoter that is independent of ttx-1. Our studies identify an important component of glia remodeling and suggest that transcriptional changes may underlie glial morphological plasticity in the sensory organs of C. elegans.

  12. Mesenteric resistance arteries in type 2 diabetic db/db mice undergo outward remodeling.

    Directory of Open Access Journals (Sweden)

    Flavia M Souza-Smith

    Full Text Available Resistance vessel remodeling is controlled by myriad of hemodynamic and neurohormonal factors. This study characterized structural and molecular remodeling in mesenteric resistance arteries (MRAs in diabetic (db/db and control (Db/db mice.Structural properties were assessed in isolated MRAs from 12 and 16 wk-old db/db and Db/db mice by pressure myography. Matrix regulatory proteins were measured by Western blot analysis. Mean arterial pressure and superior mesenteric blood flow were measured in 12 wk-old mice by telemetry and a Doppler flow nanoprobe, respectively.Blood pressure was similar between groups. Lumen diameter and medial cross-sectional area were significantly increased in 16 wk-old db/db MRA compared to control, indicating outward hypertrophic remodeling. Moreover, wall stress and cross-sectional compliance were significantly larger in diabetic arteries. These remodeling indices were associated with increased expression of matrix regulatory proteins matrix metalloproteinase (MMP-9, MMP-12, tissue inhibitors of matrix metalloproteinase (TIMP-1, TIMP-2, and plasminogen activator inhibitor-1 (PAI-1 in db/db arteries. Finally, superior mesenteric artery blood flow was increased by 46% in 12 wk-old db/db mice, a finding that preceded mesenteric resistance artery remodeling.These data suggest that flow-induced hemodynamic changes may supersede the local neurohormonal and metabolic milieu to culminate in hypertrophic outward remodeling of type 2 DM mesenteric resistance arteries.

  13. Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling (United States)

    Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.


    To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

  14. β2-Microglobulin and TIMP1 Are Linked Together in Cardiorenal Remodeling and Failure. (United States)

    Vianello, Annamaria; Caponi, Laura; Galetta, Fabio; Franzoni, Ferdinando; Taddei, Marco; Rossi, Marco; Pietrini, Pietro; Santoro, Gino


    The cardiorenal syndrome is a complication in patients hospitalized with chronic heart failure (CHF). The β2-microglobulin (b2M) level is an index of decreased glomerular filtration rate (GFR), tissue turnover and inflammation. It is an emerging new predictive marker of cardiovascular events and mortality, but its role as a biomarker of cardiorenal remodeling and failure is still unknown. TIMP1, an endogenous tissue inhibitor of activated matrix metalloproteinases, is a biomarker of heart remodeling and failure. We aimed to evaluate the circulating profile of b2M and TIMP1 in CHF patients, in sedentary controls with no tissue remodeling and in veteran athletes with physiological cardiorenal remodeling and athlete's heart (AH). We investigated the plasma levels of b2M and TIMP1 in 24 subjects with CHF without primitive renal disease, in 25 sedentary controls and in 30 veteran marathoners with AH over 50 years. The b2M and TIMP1 levels were higher in CHF patients, and there was a correlation between them (r = 0.5287, p cardiorenal impairment: with proBNP (r = 0.66, p > 0.0007), percent ejection fraction (r = -0.56, p = 0.0162) and GFR (r = 0.83, p cardiorenal failure. Moreover, a strong correlation between b2M and TIMP1 characterized cardiovascular remodeling not only in CHF patients but also in AH subjects. These findings suggest that clinicians should use b2M and TIMP1 as associated biomarkers of cardiorenal remodeling and failure.

  15. Right ventricular relative wall thickness as a predictor of outcomes and of right ventricular reverse remodeling for patients with pulmonary hypertension


    Sano, Hiroyuki; Tanaka, Hidekazu; Motoji, Yoshiki; Fukuda, Yuko; Mochizuki, Yasuhide; Hatani, Yutaka; Matsuzoe, Hiroki; Hatazawa, Keiko; Shimoura, Hiroyuki; Ooka, Junichi; Ryo-Koriyama, Keiko; Nakayama, Kazuhiko; Matsumoto, Kensuke; Emoto, Noriaki; Hirata, Ken-ichi


    Mid-term right ventricular (RV) reverse remodeling after treatment in patients with pulmonary hypertension (PH) is associated with long-term outcome as well as baseline RV remodeling. However, baseline factors influencing mid-term RV reverse remodeling after treatment and its prognostic capability remain unclear. We studied 54 PH patients. Mid-term RV remodeling was assessed in terms of the RV area, which was traced planimetrically at the end-systole (RVESA). RV reverse remodeling was defined...

  16. Metabolic remodeling of white adipose tissue in obesity. (United States)

    Cummins, Timothy D; Holden, Candice R; Sansbury, Brian E; Gibb, Andrew A; Shah, Jasmit; Zafar, Nagma; Tang, Yunan; Hellmann, Jason; Rai, Shesh N; Spite, Matthew; Bhatnagar, Aruni; Hill, Bradford G


    Adipose tissue metabolism is a critical regulator of adiposity and whole body energy expenditure; however, metabolic changes that occur in white adipose tissue (WAT) with obesity remain unclear. The purpose of this study was to understand the metabolic and bioenergetic changes occurring in WAT with obesity. Wild-type (C57BL/6J) mice fed a high-fat diet (HFD) showed significant increases in whole body adiposity, had significantly lower V̇(O₂), V̇(CO₂), and respiratory exchange ratios, and demonstrated worsened glucose and insulin tolerance compared with low-fat-fed mice. Metabolomic analysis of WAT showed marked changes in lipid, amino acid, carbohydrate, nucleotide, and energy metabolism. Tissue levels of succinate and malate were elevated, and metabolites that could enter the Krebs cycle via anaplerosis were mostly diminished in high-fat-fed mice, suggesting altered mitochondrial metabolism. Despite no change in basal oxygen consumption or mitochondrial DNA abundance, citrate synthase activity was decreased by more than 50%, and responses to FCCP were increased in WAT from mice fed a high-fat diet. Moreover, Pgc1a was downregulated and Cox7a1 upregulated after 6 wk of HFD. After 12 wk of high-fat diet, the abundance of several proteins in the mitochondrial respiratory chain or matrix was diminished. These changes were accompanied by increased Parkin and Pink1, decreased p62 and LC3-I, and ultrastructural changes suggestive of autophagy and mitochondrial remodeling. These studies demonstrate coordinated restructuring of metabolism and autophagy that could contribute to the hypertrophy and whitening of adipose tissue in obesity. Copyright © 2014 the American Physiological Society.

  17. Rule-based model of vein graft remodeling.

    Directory of Open Access Journals (Sweden)

    Minki Hwang

    Full Text Available When vein segments are implanted into the arterial system for use in arterial bypass grafting, adaptation to the higher pressure and flow of the arterial system is accomplished thorough wall thickening and expansion. These early remodeling events have been found to be closely coupled to the local hemodynamic forces, such as shear stress and wall tension, and are believed to be the foundation for later vein graft failure. To further our mechanistic understanding of the cellular and extracellular interactions that lead to global changes in tissue architecture, a rule-based modeling method is developed through the application of basic rules of behaviors for these molecular and cellular activities. In the current method, smooth muscle cell (SMC, extracellular matrix (ECM, and monocytes are selected as the three components that occupy the elements of a grid system that comprise the developing vein graft intima. The probabilities of the cellular behaviors are developed based on data extracted from in vivo experiments. At each time step, the various probabilities are computed and applied to the SMC and ECM elements to determine their next physical state and behavior. One- and two-dimensional models are developed to test and validate the computational approach. The importance of monocyte infiltration, and the associated effect in augmenting extracellular matrix deposition, was evaluated and found to be an important component in model development. Final model validation is performed using an independent set of experiments, where model predictions of intimal growth are evaluated against experimental data obtained from the complex geometry and shear stress patterns offered by a mid-graft focal stenosis, where simulation results show good agreements with the experimental data.

  18. Insulin signaling regulates neurite growth during metamorphic neuronal remodeling

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    Tingting Gu


    Although the growth capacity of mature neurons is often limited, some neurons can shift through largely unknown mechanisms from stable maintenance growth to dynamic, organizational growth (e.g. to repair injury, or during development transitions. During insect metamorphosis, many terminally differentiated larval neurons undergo extensive remodeling, involving elimination of larval neurites and outgrowth and elaboration of adult-specific projections. Here, we show in the fruit fly, Drosophila melanogaster (Meigen, that a metamorphosis-specific increase in insulin signaling promotes neuronal growth and axon branching after prolonged stability during the larval stages. FOXO, a negative effector in the insulin signaling pathway, blocked metamorphic growth of peptidergic neurons that secrete the neuropeptides CCAP and bursicon. RNA interference and CCAP/bursicon cell-targeted expression of dominant-negative constructs for other components of the insulin signaling pathway (InR, Pi3K92E, Akt1, S6K also partially suppressed the growth of the CCAP/bursicon neuron somata and neurite arbor. In contrast, expression of wild-type or constitutively active forms of InR, Pi3K92E, Akt1, Rheb, and TOR, as well as RNA interference for negative regulators of insulin signaling (PTEN, FOXO, stimulated overgrowth. Interestingly, InR displayed little effect on larval CCAP/bursicon neuron growth, in contrast to its strong effects during metamorphosis. Manipulations of insulin signaling in many other peptidergic neurons revealed generalized growth stimulation during metamorphosis, but not during larval development. These findings reveal a fundamental shift in growth control mechanisms when mature, differentiated neurons enter a new phase of organizational growth. Moreover, they highlight strong evolutionarily conservation of insulin signaling in neuronal growth regulation.

  19. Peripheral nerve injury induces adult brain neurogenesis and remodelling. (United States)

    Rusanescu, Gabriel; Mao, Jianren


    Unilateral peripheral nerve chronic constriction injury (CCI) has been widely used as a research model of human neuropathic pain. Recently, CCI has been shown to induce spinal cord adult neurogenesis, which may contribute to the chronic increase in nociceptive sensitivity. Here, we show that CCI also induces rapid and profound asymmetrical anatomical rearrangements in the adult rodent cerebellum and pons. This remodelling occurs throughout the hindbrain, and in addition to regions involved in pain processing, also affects other sensory modalities. We demonstrate that these anatomical changes, partially reversible in the long term, result from adult neurogenesis. Neurogenic markers Mash1, Ngn2, doublecortin and Notch3 are widely expressed in the rodent cerebellum and pons, both under normal and injured conditions. CCI-induced hindbrain structural plasticity is absent in Notch3 knockout mice, a strain with impaired neuronal differentiation, demonstrating its dependence on adult neurogenesis. Grey matter and white matter structural changes in human brain, as a result of pain, injury or learned behaviours have been previously detected using non-invasive neuroimaging techniques. Because neurogenesis-mediated structural plasticity is thought to be restricted to the hippocampus and the subventricular zone, such anatomical rearrangements in other parts of the brain have been thought to result from neuronal plasticity or glial hypertrophy. Our findings suggest the presence of extensive neurogenesis-based structural plasticity in the adult mammalian brain, which may maintain a memory of basal sensory levels, and act as an adaptive mechanism to changes in sensory inputs. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  20. Remodeling of bovine oviductal epithelium by mitosis of secretory cells. (United States)

    Ito, Sayaka; Kobayashi, Yoshihiko; Yamamoto, Yuki; Kimura, Koji; Okuda, Kiyoshi


    Two types of oviductal epithelial cells, secretory and ciliated, play crucial roles in the first days after fertilization in mammals. Secretory cells produce various molecules promoting embryo development, while ciliated cells facilitate transport of oocytes and zygotes by ciliary beating. The proportions of the two cell types change during the estrous cycle. The proportion of ciliated cells on the oviductal luminal surface is abundant at the follicular phase, whereas the proportion of secretory cells gradually increases with the formation of the corpus luteum. In the present study, we hypothesize that the proportions of ciliated and secretory epithelial cells are regulated by mitosis. The proportion of the cells being positive for FOXJ1 (a ciliated cell marker) or Ki67 (a mitosis marker) in epithelial cells during the estrous cycle were immunohistochemically examined. Ki67 and FOXJ1 or PAX8 (a secretory cell marker), were double-stained to clarify which types of epithelial cells undergo mitosis. In the ampulla, the percentage of FOXJ1-positive cells was highest at the day of ovulation (Day 0) and decreased by about 50 % by Days 8-12, while in the isthmus it did not change during the estrous cycle. The proportion of Ki67-positive cells was highest at around the time of ovulation in both the ampulla and isthmus. All the Ki67-positive cells were PAX8-positive and FOXJ1-negative in both the ampulla and isthmus. These findings suggest that epithelial remodeling, which is regulated by differentiation and/or proliferation of secretory cells of the oviduct, provides the optimal environment for gamete transport, fertilization and embryonic development.

  1. p38 MAPK signaling in postnatal tendon growth and remodeling.

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    Andrew J Schwartz

    Full Text Available Tendon is a dynamic tissue whose structure and function is influenced by mechanical loading, but little is known about the fundamental mechanisms that regulate tendon growth and remodeling in vivo. Data from cultured tendon fibroblasts indicated that the p38 MAPK pathway plays an important role in tendon fibroblast proliferation and collagen synthesis in vitro. To gain greater insight into the mechanisms of tendon growth, and explore the role of p38 MAPK signaling in this process, we tested the hypotheses that inducing plantaris tendon growth through the ablation of the synergist Achilles tendon would result in rapid expansion of a neotendon matrix surrounding the original tendon, and that treatment with the p38 MAPK inhibitor SB203580 would prevent this growth. Rats were treated with vehicle or SB203580, and subjected to synergist ablation by bilateral tenectomy of the Achilles tendon. Changes in histological and biochemical properties of plantaris tendons were analyzed 3, 7, or 28 days after overload, and comparisons were made to non-overloaded animals. By 28 days after overload, tendon mass had increased by 30% compared to non-overloaded samples, and cross-sectional area (CSA increased by around 50%, with most of the change occurring in the neotendon. The expansion in CSA initially occurred through the synthesis of a hyaluronic acid rich matrix that was progressively replaced with mature collagen. Pericytes were present in areas of active tendon growth, but never in the original tendon ECM. Inhibition of p38 MAPK resulted in a profound decrease in IL6 expression, and had a modest effect on the expression of other ECM and cell proliferation genes, but had a negligible impact on overall tendon growth. The combined results from this study provided novel insights into tendon mechanobiology, and suggest that p38 MAPK signaling does not appear to be necessary for tendon growth in vivo.

  2. Hemodynamic characteristics of hyperplastic remodeling lesions in cerebral aneurysms.

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    Kazuhiro Furukawa

    Full Text Available Hyperplastic remodeling (HR lesions are sometimes found on cerebral aneurysm walls. Atherosclerosis is the results of HR, which may cause an adverse effect on surgical treatment for cerebral aneurysms. Previous studies have demonstrated that atherosclerotic changes had a correlation with certain hemodynamic characteristics. Therefore, we investigated local hemodynamic characteristics of HR lesions of cerebral aneurysms using computational fluid dynamics (CFD.Twenty-four cerebral aneurysms were investigated using CFD and intraoperative video recordings. HR lesions and red walls were confirmed on the intraoperative images, and the qualification points were determined on the center of the HR lesions and the red walls. The qualification points were set on the virtual operative images for evaluation of wall shear stress (WSS, normalized WSS (NWSS, oscillatory shear index (OSI, relative residence time (RRT, and aneurysm formation indicator (AFI. These hemodynamic parameters at the qualification points were compared between HR lesions and red walls.HR lesions had lower NWSS, lower AFI, higher OSI and prolonged RRT compared with red walls. From analysis of the receiver-operating characteristic curve for hemodynamic parameters, OSI was the most optimal hemodynamic parameter to predict HR lesions (area under the curve, 0.745; 95% confidence interval, 0.603-0.887; cutoff value, 0.00917; sensitivity, 0.643; specificity, 0.893; P<0.01. With multivariate logistic regression analyses using stepwise method, NWSS was significantly associated with the HR lesions.Although low NWSS was independently associated with HR lesions, OSI is the most valuable hemodynamic parameter to distinguish HR lesions from red walls.

  3. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

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    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  4. Leukocyte diversity in resolving and nonresolving mechanisms of cardiac remodeling. (United States)

    Tourki, Bochra; Halade, Ganesh


    of cardiac remodeling. © FASEB.

  5. Analogy of strain energy density based bone-remodeling algorithm and structural topology optimization. (United States)

    Jang, In Gwun; Kim, Il Yong; Kwak, Byung Ban


    In bone-remodeling studies, it is believed that the morphology of bone is affected by its internal mechanical loads. From the 1970s, high computing power enabled quantitative studies in the simulation of bone remodeling or bone adaptation. Among them, Huiskes et al. (1987, "Adaptive Bone Remodeling Theory Applied to Prosthetic Design Analysis," J. Biomech. Eng., 20, pp. 1135-1150) proposed a strain energy density based approach to bone remodeling and used the apparent density for the characterization of internal bone morphology. The fundamental idea was that bone density would increase when strain (or strain energy density) is higher than a certain value and bone resorption would occur when the strain (or strain energy density) quantities are lower than the threshold. Several advanced algorithms were developed based on these studies in an attempt to more accurately simulate physiological bone-remodeling processes. As another approach, topology optimization originally devised in structural optimization has been also used in the computational simulation of the bone-remodeling process. The topology optimization method systematically and iteratively distributes material in a design domain, determining an optimal structure that minimizes an objective function. In this paper, we compared two seemingly different approaches in different fields-the strain energy density based bone-remodeling algorithm (biomechanical approach) and the compliance based structural topology optimization method (mechanical approach)-in terms of mathematical formulations, numerical difficulties, and behavior of their numerical solutions. Two numerical case studies were conducted to demonstrate their similarity and difference, and then the solution convergences were discussed quantitatively.

  6. The PDE4 inhibitor CHF-6001 and LAMAs inhibit bronchoconstriction-induced remodeling in lung slices. (United States)

    Kistemaker, Loes E M; Oenema, Tjitske A; Baarsma, Hoeke A; Bos, I Sophie T; Schmidt, Martina; Facchinetti, Fabrizio; Civelli, Maurizio; Villetti, Gino; Gosens, Reinoud


    Combination therapy of PDE4 inhibitors and anticholinergics induces bronchoprotection in COPD. Mechanical forces that arise during bronchoconstriction may contribute to airway remodeling. Therefore, we investigated the impact of PDE4 inhibitors and anticholinergics on bronchoconstriction-induced remodeling. Because of the different mechanism of action of PDE4 inhibitors and anticholinergics, we hypothesized functional interactions of these two drug classes. Guinea pig precision-cut lung slices were preincubated with the PDE4 inhibitors CHF-6001 or roflumilast and/or the anticholinergics tiotropium or glycopyorrolate, followed by stimulation with methacholine (10 μM) or TGF-β1 (2 ng/ml) for 48 h. The inhibitory effects on airway smooth muscle remodeling, airway contraction, and TGF-β release were investigated. Methacholine-induced protein expression of smooth muscle-myosin was fully inhibited by CHF-6001 (0.3-100 nM), whereas roflumilast (1 µM) had smaller effects. Tiotropium and glycopyrrolate fully inhibited methacholine-induced airway remodeling (0.1-30 nM). The combination of CHF-6001 and tiotropium or glycopyrrolate, in concentrations partially effective by themselves, fully inhibited methacholine-induced remodeling in combination. CHF-6001 did not affect airway closure and had limited effects on TGF-β1-induced remodeling, but rather, it inhibited methacholine-induced TGF-β release. The PDE4 inhibitor CHF-6001, and to a lesser extent roflumilast, and the LAMAs tiotropium and glycopyrrolate inhibit bronchoconstriction-induced remodeling. The combination of CHF-6001 and anticholinergics was more effective than the individual compounds. This cooperativity might be explained by the distinct mechanisms of action inhibiting TGF-β release and bronchoconstriction. Copyright © 2017 the American Physiological Society.

  7. Candesartan cilexetil attenuated cardiac remodeling by improving expression and function of mitofusin 2 in SHR. (United States)

    Wang, Zuoguang; Niu, Qiuli; Peng, Xiaoyun; Li, Mei; Liu, Kuo; Liu, Ya; Liu, Jielin; Jin, Fei; Li, Xiao; Wei, Yongxiang


    Left ventricular hypotrophy (LVH) is very common in hypertensives even after antihypertensive treatment. Mitofusin 2 (Mfn2) is a critical negative regulator of vascular smooth muscle cell (VSMC) hypertrophy by regulating mitochondrial fusion, ras/raf/MEK signal pathway, et al. The purpose of this study was to investigate whether candesartan attenuated cardiac remodeling by improving expression and function of mitofusin 2 in SHR. Nine weeks old spontaneously hypertensive rats (SHR) were selected and treated with candesartan for eight weeks. Then, heart tissues were investigated for signs of cardiac remodeling, mitochondrial structure and membrane potential, mitochondrial enzyme activities, hydrogen peroxide, mRNA and protein expression of Mfn2/ras/raf/MEK signaling pathway in heart tissues. The results showed that cardiac remodeling was obviously in SHR group: cardiac cell alignment was irregular; cardiac fibers became thick, irregular and enlarged; cell density was reduced in SHR compared to WKY. After candesartan treatment, histopathological structure improved significantly which were consistent with mitochondrial morphology, mitochondrial membrane potential, mitochondrial enzyme activities, hydrogen peroxide, Mfn2/ras/raf/MEK gene and protein expression in cardiac tissues. What's more, although blood pressure was well controlled in a normal range, cardiac remodeling wasn't avoided. In general, candesartan obviously repressed cardiac hypertrophy and cardiac remodeling significantly compared to SHR untreated group, but didn't reverse it. Mfn2 is negatively associated with cardiac remodeling. Candesartan treatment can improve mitochondrial structure and function and regulate Mfn2/ras/raf/MEK signaling pathway. Mfn2 may be used a potential marker for cardiac remodeling and a novel therapeutic target for target organ damage protection. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Prediction of Left Ventricular Remodeling after a Myocardial Infarction: Role of Myocardial Deformation: A Systematic Review and Meta-Analysis.

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    Olivier Huttin

    Full Text Available Left ventricular (LV adverse or reverse remodeling after ST-segment elevation myocardial infarction (MI is the best outcome to assess the benefit of revascularization. Speckle tracking echocardiography (STE may accurately identify early deformation impairment, while also being predictive of LV remodeling during follow-up. This systematic analysis aimed to provide a comprehensive review of current findings on STE as a predictor of LV remodeling after MI.PubMed databases were searched through December 2014 to identify studies in adults targeting the association between LV remodeling and STE. Meta-regression was performed for longitudinal analysis.A total of 23 prospective studies (3066 patients were found eligible. Eleven studies reported an association between STE and adverse remodeling and twelve studies with reverse remodeling. Using peak systolic longitudinal strain, the most accurate cut-off to predict adverse remodeling and reverse remodeling ranged from -12.8% to -10.2% and from -13.7% to -9.5%, respectively. In smaller studies, assessment of circumferential strain and torsion showed additive value in predicting remodeling. Meta-regression analysis revealed that longitudinal STE was associated with adverse remodeling (pooled univariable OR = 1.27, 1.17-1.38, p<0.001; pooled multivariable OR = 1.38, 1.13-1.70, p = 0.002 while pooled ORs of longitudinal STE only tended to predict reverse remodeling (pooled OR = 0.75, 0.54-1.06, p = 0.09.This systematic review suggests that STE is associated with changes in LV volume or function regardless of underlying mechanisms and deformation direction. Meta-regression demonstrates a strong association between peak longitudinal systolic strain and adverse remodeling. Added STE predictive value over other clinical, biological and imaging variables remains to be proven.

  9. Dynamic remodeling of microbial biofilms by functionally distinct exopolysaccharides. (United States)

    Chew, Su Chuen; Kundukad, Binu; Seviour, Thomas; van der Maarel, Johan R C; Yang, Liang; Rice, Scott A; Doyle, Patrick; Kjelleberg, Staffan


    Biofilms are densely populated communities of microbial cells protected and held together by a matrix of extracellular polymeric substances. The structure and rheological properties of the matrix at the microscale influence the retention and transport of molecules and cells in the biofilm, thereby dictating population and community behavior. Despite its importance, quantitative descriptions of the matrix microstructure and microrheology are limited. Here, particle-tracking microrheology in combination with genetic approaches was used to spatially and temporally study the rheological contributions of the major exopolysaccharides Pel and Psl in Pseudomonas aeruginosa biofilms. Psl increased the elasticity and effective cross-linking within the matrix, which strengthened its scaffold and appeared to facilitate the formation of microcolonies. Conversely, Pel reduced effective cross-linking within the matrix. Without Psl, the matrix becomes more viscous, which facilitates biofilm spreading. The wild-type biofilm decreased in effective cross-linking over time, which would be advantageous for the spreading and colonization of new surfaces. This suggests that there are regulatory mechanisms to control production of the exopolysaccharides that serve to remodel the matrix of developing biofilms. The exopolysaccharides were also found to have profound effects on the spatial organization and integration of P. aeruginosa in a mixed-species biofilm model of P. aeruginosa-Staphylococcus aureus. Pel was required for close association of the two species in mixed-species microcolonies. In contrast, Psl was important for P. aeruginosa to form single-species biofilms on top of S. aureus biofilms. Our results demonstrate that Pel and Psl have distinct physical properties and functional roles during biofilm formation. Importance: Most bacteria grow as biofilms in the environment or in association with eukaryotic hosts. Removal of biofilms that form on surfaces is a challenge in clinical

  10. CT-1-CP-induced ventricular electrical remodeling in mice. (United States)

    Chen, Shu-fen; Wei, Tao-zhi; Rao, Li-ya; Xu, Ming-guang; Dong, Zhan-ling


    The chronic effects of carboxyl-terminal polypeptide of Cardiotrophin-1 (CT-1-CP) on ventricular electrical remodeling were investigated. CT-1-CP, which contains 16 amino acids in sequence of the C-terminal of Cardiotrophin-1, was selected and synthesized, and then administered to Kunming mice (aged 5 weeks) by intraperitoneal injection (500 ng·g⁻¹·day⁻¹) (4 groups, n=10 and female: male=1:1 in each group) for 1, 2, 3 and 4 weeks, respectively. The control group (n=10, female: male=1:1) was injected by physiological saline for 4 weeks. The epicardial monophasic action potential (MAP) was recorded by using a contact-type MAP electrode placed vertically on the left ventricular (LV) epicardium surface, and the electrocardiogram (ECG) signal in lead II was monitored synchronously. ECG intervals (RR, PR, QRS and QT) and the amplitude of MAP (Am), the maximum upstroke velocity (Vmax), as well as action potential durations (APDs) at different repolarization levels (APD30, APD50, APD70, and APD90) of MAP were determined and analyzed in detail. There were no significant differences in RR and P intervals between CT-1-CP-treated groups and control group, but the PR segment and the QRS complex were greater in the former than in the latter (F=2.681 and 5.462 respectively, PCP-treated groups than in control group, the QT dispersion (QTd) of them was greater in the latter than in the former (F=3.090, PCP-treated groups and the prolongation of QT intervals increased gradually along with the time of exposure to CT-1-CP. The QRS complex had no significant change in control group, one-week and three-week CT-1-CP-treated groups, but prolonged significantly in two-week and four-week CT-1-CP-treated groups. Interestingly, the QTd after chest-opening was significantly greater than that before chest-opening in control group (t=5.242, PCP-treated groups. The mean MAP amplitude, Vmax and APD were greater in CT-1-CP-treated groups than those in control group, and became more obvious

  11. The role of air pollution in myocardial remodeling.

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    A M de Oliveira-Fonoff

    Full Text Available Excessive air pollution in urban environments can impact morbidity and mortality. The authors evaluated the role of particulate matter2.5 (PM2.5 in structural, geometric, and functional remodeling in hearts, using an experimental model of myocardial infarction.Seventy-five rats were divided into 5 groups: control (CG, CG exposed to PM2.5 pollution (CGP, myocardial infarcted group (MI, infarcted group immediately exposed to pollution (IGP-I, and infarcted group previously exposed to pollution and kept exposed after infarction (IGP-II. Greater deposition of interstitial collagen occurred in the left ventricle in CGP, MI, IGP-I, and IGP-II groups compared with that in controls (p = 0.002 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II. In the right ventricle, greater collagen deposition existed in CGP, MI, IGP-I, and IGP-II compared with that in CG (p<0.021 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II. At the end of the study, CG had a higher mean shortening fraction than the other groups had (p≤0.03. Left ventricular systolic diameter was lower in CG than in infarcted groups (p≤0.003. The infarcted groups had greater expression of TGF-β (p≤0.04. PM2.5 increased the expression of TGF-β in the IGP-II compared with the MI group (p = 0.004. The TNF-α gene was overexpressed in the IGP-II compared with the CGP group (p = 0.012. INF-γ gene expression was greater in IGP-II (p≤0.01. Oxidative stress analysis showed a higher glutathione concentration in CGP (p = 0.03, MI (p = 0.014, and IGP-I (p = 0.008 compared with that in CG.PM2.5 stimulates the deposition of fibrosis in the myocardium of healthy hearts, but not in infarcted hearts. PM2.5 modulates the inflammatory response, which was greater in the IGP-II group. It also modulates oxidative stress in healthy hearts but not in infarcted hearts.

  12. The role of air pollution in myocardial remodeling. (United States)

    de Oliveira-Fonoff, A M; Mady, C; Pessoa, F G; Fonseca, K C B; Salemi, V M C; Fernandes, F; Saldiva, P H N; Ramires, F J A


    Excessive air pollution in urban environments can impact morbidity and mortality. The authors evaluated the role of particulate matter2.5 (PM2.5) in structural, geometric, and functional remodeling in hearts, using an experimental model of myocardial infarction. Seventy-five rats were divided into 5 groups: control (CG), CG exposed to PM2.5 pollution (CGP), myocardial infarcted group (MI), infarcted group immediately exposed to pollution (IGP-I), and infarcted group previously exposed to pollution and kept exposed after infarction (IGP-II). Greater deposition of interstitial collagen occurred in the left ventricle in CGP, MI, IGP-I, and IGP-II groups compared with that in controls (p = 0.002 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). In the right ventricle, greater collagen deposition existed in CGP, MI, IGP-I, and IGP-II compared with that in CG (p<0.021 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). At the end of the study, CG had a higher mean shortening fraction than the other groups had (p≤0.03). Left ventricular systolic diameter was lower in CG than in infarcted groups (p≤0.003). The infarcted groups had greater expression of TGF-β (p≤0.04). PM2.5 increased the expression of TGF-β in the IGP-II compared with the MI group (p = 0.004). The TNF-α gene was overexpressed in the IGP-II compared with the CGP group (p = 0.012). INF-γ gene expression was greater in IGP-II (p≤0.01). Oxidative stress analysis showed a higher glutathione concentration in CGP (p = 0.03), MI (p = 0.014), and IGP-I (p = 0.008) compared with that in CG. PM2.5 stimulates the deposition of fibrosis in the myocardium of healthy hearts, but not in infarcted hearts. PM2.5 modulates the inflammatory response, which was greater in the IGP-II group. It also modulates oxidative stress in healthy hearts but not in infarcted hearts.

  13. Histomorphometric study of trabecular bone remodeling during condylar process fracture healing in the growing period: experimental study. (United States)

    Yasuoka, T; Oka, N


    Trabecular bone remodeling during condylar fracture healing in the growing period was analyzed by histomorphometry with a synchronous system. Data from the study showed displacement of the fractured condyle was compensated by the changes in remodeling ascribed to the pubertal spurt of growth, and that such remodeling still continued even after clinical healing. The regional acceleratory phenomenon, evolved to potentiate tissue healing, was observed 1 week after induction of the fracture. Mesenchymal cells were presumably modulated into chondroblasts that promoted endochondral ossification. It was concluded that trabecular bone remodeling plays an important role in healing of condylar fractures during the growth period.

  14. Yiqihuoxuejiedu Formula Inhibits Vascular Remodeling by Reducing Proliferation and Secretion of Adventitial Fibroblast after Balloon Injury

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    Ming-Jing Zhao


    Full Text Available Vascular remodeling occurs in atherosclerosis, hypertension, and restenosis after percutaneous coronary intervention. Adventitial remodeling may be a potential therapeutic target. Yiqihuoxuejiedu formula uses therapeutic principles from Chinese medicine to supplement Qi, activate blood circulation, and resolve toxin and it has been shown to inhibit vascular stenosis. To investigate effects and mechanisms of the formula on inhibiting vascular remodeling, especially adventitial remodeling, rats with a balloon injury to their common carotid artery were used and were treated for 7 or 28 days after injury. The adventitial area and α-SMA expression increased at 7 days after injury, which indicated activation and proliferation of adventitial fibroblasts. Yiqihuoxuejiedu formula reduced the adventitial areas at 7 days, attenuated the neointima and vessel wall area, stenosis percent, and α-SMA expression in the neointima, and reduced collagen content and type I/III collagen ratio in the adventitia at 28 days. Yiqihuoxuejiedu formula had more positive effects than Captopril in reducing intimal proliferation and diminishing stenosis, although Captopril lowered neointimal α-SMA expression and reduced the collagen content at 28 days. Yiqihuoxuejiedu formula has inhibitory effects on positive and negative remodeling by reducing adventitial and neointimal proliferation, reducing content, and elevating adventitial compliance.

  15. Mechanical remodeling of normally sized mammalian cells under a gravity vector. (United States)

    Zhang, Chen; Zhou, Lüwen; Zhang, Fan; Lü, Dongyuan; Li, Ning; Zheng, Lu; Xu, Yanhong; Li, Zhan; Sun, Shujin; Long, Mian


    Translocation of the dense nucleus along a gravity vector initiates mechanical remodeling of a cell, but the underlying mechanisms of cytoskeletal network and focal adhesion complex (FAC) reorganization in a mammalian cell remain unclear. We quantified the remodeling of an MC3T3-E1 cell placed in upward-, downward-, or edge-on-orientated substrate. Nucleus longitudinal translocation presents a high value in downward orientation at 24 h or in edge-on orientation at 72 h, which is consistent with orientation-dependent distribution of perinuclear actin stress fibers and vimentin cords. Redistribution of total FAC area and fractionized super mature adhesion number coordinates this dependence at short duration. This orientation-dependent remodeling is associated with nucleus flattering and lamin A/C phosphorylation. Actin depolymerization or Rho-associated protein kinase signaling inhibition abolishes the orientation dependence of nucleus translocation, whereas tubulin polymerization inhibition or vimentin disruption reserves the dependence. A biomechanical model is therefore proposed for integrating the mechanosensing of nucleus translocation with cytoskeletal remodeling and FAC reorganization induced by a gravity vector.-Zhang, C., Zhou, L., Zhang, F., Lü, D., Li, N., Zheng, L., Xu, Y., Li, Z., Sun, S., Long, M. Mechanical remodeling of normally sized mammalian cells under a gravity vector. © FASEB.

  16. Gender-related differences in β-adrenergic receptor-mediated cardiac remodeling. (United States)

    Zhu, Baoling; Liu, Kai; Yang, Chengzhi; Qiao, Yuhui; Li, Zijian


    Cardiac remodeling is the pathological basis of various cardiovascular diseases. In this study, we found gender-related differences in β-adrenergic receptor (AR)-mediated pathological cardiac remodeling. Cardiac remodeling model was established by subcutaneous injection of isoprenaline (ISO) for 14 days. Heart rate (HR), mean arterial pressure (MAP), and echocardiography were obtained on 7th and 14th days during ISO administration. Myocardial cross-sectional area and the ratio of heart mass to tibia length (HM/TL) were detected to assess cardiac hypertrophy. Picro-Sirius red staining (picric acid + Sirius red F3B) was used to evaluate cardiac fibrosis. Myocardial capillary density was assessed by immunohistochemistry for von Willebrand factor. Further, real-time PCR was used to measure the expression of β1-AR and β2-AR. Results showed that ISO induced cardiac remodeling, the extent of which was different between female and male mice. The extent of increase in cardiac wall thickness, myocardial cross-sectional area, and collagen deposition in females was less than that in males. However, no gender-related difference was observed in HR, MAP, cardiac function, and myocardial capillary density. The distinctive decrease of β2-AR expression, rather than a decrease of β1-AR expression, seemed to result in gender-related differences in cardiac remodeling.

  17. Evidence for Myelin Sheath Remodeling in the CNS Revealed by In Vivo Imaging. (United States)

    Auer, Franziska; Vagionitis, Stavros; Czopka, Tim


    The length of myelin sheaths affects conduction speed along axons and information propagation. It has recently become clear that myelin may be adaptively modified to modulate circuit function, implying that length remodeling of myelin sheaths should occur. However, direct evidence for such events is lacking. We have investigated how myelination patterns are formed, maintained, and remodeled using long-term imaging and myelin ablation in zebrafish. We demonstrate that length differences between myelin sheaths are established by rapid and variable growth within 3 days after their formation, independently of their time of formation, and even along discontinuously myelinated axons. Afterward, sheaths continue extending at similar rates to compensate for overall animal growth. In consequence, once axon myelination patterns are established, they are maintained over long periods of time. We tested whether mature myelin sheaths can remodel by removing individual sheaths from single axons by targeted ablation. Remarkably, extensive changes in sheath length and number occurred, which frequently restored the original myelination pattern. Our results show that axons can control myelin growth and remodeling, and we provide evidence for a homeostatic control of axon myelination patterns by maintenance and remodeling of myelin sheath length, with implications for circuit development, function, and repair. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  18. Home Remodeling and Food Allergy Interact Synergistically to Increase the Risk of Atopic Dermatitis

    Directory of Open Access Journals (Sweden)

    Won Seok Lee


    Full Text Available Purpose. The purpose of this study was to investigate the effects of home remodeling and food allergy (FA on the development of atopic dermatitis (AD in children. Methods. The Modified International Study of Asthma and Allergies in Childhood questionnaire was used to survey 4,111 children recruited from 3 kindergartens and 6 elementary schools from Seongnam, Korea. Participants’ parents agreed for them to participate in physical examinations, skin prick tests, and blood tests. Results. Home remodeling in the past 12 months (adjusted odds ratio [aOR] 3.40, P=0.006, lifetime diagnosis of FA (aOR 3.95, P<0.001, parental history of AD (aOR 2.67, P=0.001, and FA (aOR 2.35, P=0.004 were independent risk factors for lifetime diagnosis of AD ever. When history of home remodeling and FA were combined, the risk for moderate-to-severe AD by scoring atopic dermatitis (SCORAD score increased (aOR, 7.19, P=0.011, P for interaction = 0.034. Conclusion. Home remodeling, lifetime diagnosis of FA, parental history of AD, and parental history of FA were independent risk factors for AD. In addition, we observed a synergistic interaction between home remodeling and FA in the risk of moderate-to-severe AD.

  19. Qumquad: a UML-based approach for remodeling of legacy systems in health care. (United States)

    Garde, Sebastian; Knaup, Petra; Herold, Ralf


    Health care information systems still comprise legacy systems to a certain extent. For reengineering legacy systems a thorough remodeling is inalienable. Current modeling techniques like the Unified Modeling Language (UML) do not offer a systematic and comprehensive process-oriented method for remodeling activities. We developed a systematic method for remodeling legacy systems in health care called Qumquad. Qumquad consists of three major steps: (i) modeling the actual state of the application system, (ii) systematic identification of weak points in this model and (iii) development of a target concept for the reimplementation considering the identified weak points. We applied Qumquad for remodeling a documentation and therapy planning system for pediatric oncology (DOSPO). As a result of our remodeling activities we regained an abstract model of the system, an analysis of the current weak points of DOSPO and possible (partly alternative) solutions to overcome the weak points. Qumquad proved to be very helpful in the reengineering process of DOSPO since we now have at our disposal a comprehensive model for the reimplementation of DOSPO that current users of the system agree on. Qumquad can easily be applied to other reengineering projects in health care.

  20. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

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    Sung Sik eChoe


    Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  1. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. (United States)

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum


    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  2. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer

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    Thomas R. Cox


    Full Text Available Dynamic remodeling of the extracellular matrix (ECM is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.


    Directory of Open Access Journals (Sweden)

    Gaifullin N.M.


    Full Text Available The goal of article concludes to describe the remodeling of the femur, caused by two processes: the increased strain on supporting tissue as a result of anterior cruciate ligament transection and stimulation by installation of endosseous titanium implants with a porous bioactive coating. The process is traced through 4, 8 and 12 weeks in 28 adult Wistar rats. To characterize the bone remodeling the classical methods of histology and morphometry as well as immune histochemistry to reveal osteonectin, tartrate-resistant acid phosphatase, endothelial marker СD31, matrix metalloproteinases MMP-2, MMP-9, and its tissue inhibitor TIMP-1, were used with necessary morphometrics. The study showed for bone remodelling caused by implants with a porous bioactive coating, to be superior to a similar process under conditions of overload on the bone after transection of the anterior cruciate ligament by its intensity and dynamics. This indicates a high osteoinductive effect of bioactive coating that allows not only to achieve full osseointegration, but also to stimulate a process of intensive remodeling of adjacent cancellous bone. The cooperative participation of cell populations as osteoblasts/osteocytes, osteoclasts, and endothelial cells with characteristic parallel intensive expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitor TIMP-1, used to be main characteristics of bone remodeling in these conditions.

  4. Passive solar design strategies: Remodeling guidelines for conserving energy at home. [Final report

    Energy Technology Data Exchange (ETDEWEB)


    The idea of passive solar is simple, but applying it effectively does require information and attention to the details of design and construction. Some passive solar techniques are modest and low-cost, and require only small changes in remodeler`s typical practice. At the other end of the spectrum, some passive solar systems can almost eliminate a house`s need for purchased heating (and in some cases, cooling) energy -- but probably at a relatively high first cost. In between are a broad range of energy-conserving passive solar techniques. Whether or not they are cost-effective, practical and attractive enough to offer a market advantage to any individual remodeler depends on very specific factors such as local costs, climate, and market characteristics. Passive solar design strategies: Remodeling Guidelines For Conserving Energy At Homes is written to help give remodelers the information they need to make these decisions. Passive Solar Design Strategies is a package in three basic parts: The Guidelines contain information about passive solar techniques and how they work, and provides specific examples of systems which will save various percentages of energy; The Worksheets offer a simple, fill-in-the-blank method to pre-evaluate the performance of a specific design; The Worked Example demonstrates how to complete the worksheets for a typical residence.

  5. Left ventricular remodeling in swine after myocardial infarction: a transcriptional genomics approach. (United States)

    Kuster, Diederik W D; Merkus, Daphne; Kremer, Andreas; van Ijcken, Wilfred F J; de Beer, Vincent J; Verhoeven, Adrie J M; Duncker, Dirk J


    Despite the apparent appropriateness of left ventricular (LV) remodeling following myocardial infarction (MI), it poses an independent risk factor for development of heart failure. There is a paucity of studies into the molecular mechanisms of LV remodeling in large animal species. We took an unbiased molecular approach to identify candidate transcription factors (TFs) mediating the genetic reprogramming involved in post-MI LV remodeling in swine. Left ventricular tissue was collected from remote, non-infarcted myocardium, 3 weeks after MI-induction or sham-surgery. Microarray analysis identified 285 upregulated and 278 downregulated genes (FDR two-fold (p two-fold. Five TFs were identified in both TFBS and protein/DNA array analyses, which showed matching changes for COUP-TFII and glucocorticoid receptor (GR) only. Treatment of swine with the GR antagonist mifepristone after MI reduced the post-MI increase in LV mass, but LV dilation remained unaffected. Thus, using an unbiased approach to study post-MI LV remodeling in a physiologically relevant large animal model, we identified COUP-TFII and GR as potential key mediators of post-MI remodeling.

  6. Talin Is Required Continuously for Cardiomyocyte Remodeling during Heart Growth in Drosophila.

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    Simina Bogatan

    Full Text Available Mechanotransduction of tension can govern the remodeling of cardiomyocytes during growth or cardiomyopathy. Tension is signaled through the integrin adhesion complexes found at muscle insertions and costameres but the relative importance of signalling during cardiomyocyte growth versus remodelling has not been assessed. Employing the Drosophila cardiomyocyte as a genetically amenable model, we depleted the levels of Talin, a central component of the integrin adhesion complex, at different stages of heart growth and remodeling. We demonstrate a continuous requirement for Talin during heart growth to maintain the one-to-one apposition of myofibril ends between cardiomyocytes. Retracted myofibrils cannot regenerate appositions to adjacent cells after restoration of normal Talin expression, and the resulting deficit reduces heart contraction and lifespan. Reduction of Talin during heart remodeling after hatching or during metamorphosis results in pervasive degeneration of cell contacts, myofibril length and number, for which restored Talin expression is insufficient for regeneration. Resultant dilated cardiomyopathy results in a fibrillating heart with poor rhythmicity. Cardiomyocytes have poor capacity to regenerate deficits in myofibril orientation and insertion, despite an ongoing capacity to remodel integrin based adhesions.

  7. ATP-dependent chromatin remodeling in the DNA-damage response

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    Lans Hannes


    Full Text Available Abstract The integrity of DNA is continuously challenged by metabolism-derived and environmental genotoxic agents that cause a variety of DNA lesions, including base alterations and breaks. DNA damage interferes with vital processes such as transcription and replication, and if not repaired properly, can ultimately lead to premature aging and cancer. Multiple DNA pathways signaling for DNA repair and DNA damage collectively safeguard the integrity of DNA. Chromatin plays a pivotal role in regulating DNA-associated processes, and is itself subject to regulation by the DNA-damage response. Chromatin influences access to DNA, and often serves as a docking or signaling site for repair and signaling proteins. Its structure can be adapted by post-translational histone modifications and nucleosome remodeling, catalyzed by the activity of ATP-dependent chromatin-remodeling complexes. In recent years, accumulating evidence has suggested that ATP-dependent chromatin-remodeling complexes play important, although poorly characterized, roles in facilitating the effectiveness of the DNA-damage response. In this review, we summarize the current knowledge on the involvement of ATP-dependent chromatin remodeling in three major DNA repair pathways: nucleotide excision repair, homologous recombination, and non-homologous end-joining. This shows that a surprisingly large number of different remodeling complexes display pleiotropic functions during different stages of the DNA-damage response. Moreover, several complexes seem to have multiple functions, and are implicated in various mechanistically distinct repair pathways.

  8. Ca2+ ionophores trigger membrane remodeling without a need for store-operated Ca2+ entry. (United States)

    Galitzine, Marie; Capiod, Thierry; Le Deist, Françoise; Meyer, Dominique; Freyssinet, Jean-Marie; Kerbiriou-Nabias, Danièle


    Calcium (Ca2+) ionophores are the most effective agents able to elicit rapid membrane remodeling in vitro. This process exposes aminophospholipids at the surface of platelets and blood cells, thus providing a catalytic surface for coagulation. To explore the underlying mechanism, we examined if cytosolic Ca2+ ([Ca2+]i) increase through store-operated Ca2+ entry (SOCE) was necessary for the potent effect of ionophores. Recent studies have demonstrated that the Ca2+-ATPase inhibitor thapsigargin, although able to elevate [Ca2+]i through SOCE, does not trigger the rapid membrane remodeling. However, it was not known if the additional effect of ionophores to promote the process required SOCE or could it occur independently. We took advantage of two mutant B lymphoblast cell lines, characterized either by defective SOCE or altered membrane remodeling, to simultaneously assess [Ca2+]i increase and membrane remodeling in the presence of ionophores or thapsigargin. Results imply that ionophores trigger membrane remodeling without the requirement for a functional SOCE.

  9. DNA repair goes hip-hop: SMARCA and CHD chromatin remodellers join the break dance. (United States)

    Rother, Magdalena B; van Attikum, Haico


    Proper signalling and repair of DNA double-strand breaks (DSB) is critical to prevent genome instability and diseases such as cancer. The packaging of DNA into chromatin, however, has evolved as a mere obstacle to these DSB responses. Posttranslational modifications and ATP-dependent chromatin remodelling help to overcome this barrier by modulating nucleosome structures and allow signalling and repair machineries access to DSBs in chromatin. Here we recap our current knowledge on how ATP-dependent SMARCA- and CHD-type chromatin remodellers alter chromatin structure during the signalling and repair of DSBs and discuss how their dysfunction impacts genome stability and human disease.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Authors.

  10. Remodeled articular surface after surgical fixation of patella fracture in a child

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    Moruf Babatunde Yusuf


    Full Text Available Patella fracture is uncommon in pediatric age group and their patella is better preserved in any class of patella fracture. We reported a case of a 13-year-old male with right patella fracture nonunion. He had open reduction and internal fixation using tension band wire device. Fracture union was monitored with serial radiographs and he was followed up for 60 weeks. There was articular surface step after surgical fixation of the patella fracture. At 34 weeks postoperative, there was complete remodeling of the articular surface with good knee function after removal of the tension band wire. Children have good capacity of bone remodeling after fracture. Little retropatella step in a child after patella fracture surgical fixation will remodel with healing.

  11. A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development

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    Justyna Nitarska


    Full Text Available Histone modifications and chromatin remodeling represent universal mechanisms by which cells adapt their transcriptional response to rapidly changing environmental conditions. Extensive chromatin remodeling takes place during neuronal development, allowing the transition of pluripotent cells into differentiated neurons. Here, we report that the NuRD complex, which couples ATP-dependent chromatin remodeling with histone deacetylase activity, regulates mouse brain development. Subunit exchange of CHDs, the core ATPase subunits of the NuRD complex, is required for distinct aspects of cortical development. Whereas CHD4 promotes the early proliferation of progenitors, CHD5 facilitates neuronal migration and CHD3 ensures proper layer specification. Inhibition of each CHD leads to defects of neuronal differentiation and migration, which cannot be rescued by expressing heterologous CHDs. Finally, we demonstrate that NuRD complexes containing specific CHDs are recruited to regulatory elements and modulate the expression of genes essential for brain development.

  12. Electron Transport Chain Remodeling by GSK3 during Oogenesis Connects Nutrient State to Reproduction. (United States)

    Sieber, Matthew H; Thomsen, Michael B; Spradling, Allan C


    Reproduction is heavily influenced by nutrition and metabolic state. Many common reproductive disorders in humans are associated with diabetes and metabolic syndrome. We characterized the metabolic mechanisms that support oogenesis and found that mitochondria in mature Drosophila oocytes enter a low-activity state of respiratory quiescence by remodeling the electron transport chain (ETC). This shift in mitochondrial function leads to extensive glycogen accumulation late in oogenesis and is required for the developmental competence of the oocyte. Decreased insulin signaling initiates ETC remodeling and mitochondrial respiratory quiescence through glycogen synthase kinase 3 (GSK3). Intriguingly, we observed similar ETC remodeling and glycogen uptake in maturing Xenopus oocytes, suggesting that these processes are evolutionarily conserved aspects of oocyte development. Our studies reveal an important link between metabolism and oocyte maturation. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Bone remodelling in Neanderthal mandibles from the El Sidrón site (Asturias, Spain). (United States)

    Martinez-Maza, Cayetana; Rosas, Antonio; García-Vargas, Samuel; Estalrrich, Almudena; de la Rasilla, Marco


    Skull morphology results from the bone remodelling mechanism that underlies the specific bone growth dynamics. Histological study of the bone surface from Neanderthal mandible specimens of El Sidrón (Spain) provides information about the distribution of the remodelling fields (bone remodelling patterns or BRP) indicative of the bone growth directions. In comparison with other primate species, BRP shows that Neanderthal mandibles from the El Sidrón (Spain) sample present a specific BRP. The interpretation of this map allows inferences concerning the growth directions that explain specific morphological traits of the Neanderthal mandible, such as its quadrangular shape and the posterior location of the mental foramen. This journal is © 2011 The Royal Society

  14. A secreted bacterial protease tailors the Staphylococcus aureus virulence repertoire to modulate bone remodeling during osteomyelitis (United States)

    Cassat, James E.; Hammer, Neal D.; Campbell, J. Preston; Benson, Meredith A.; Perrien, Daniel S.; Mrak, Lara N.; Smeltzer, Mark S.; Torres, Victor J.; Skaar, Eric P.


    Summary Osteomyelitis is a common manifestation of invasive Staphylococcus aureus infection. Pathogen-induced bone destruction limits antimicrobial penetration to the infectious focus and compromises treatment of osteomyelitis. To investigate mechanisms of S. aureus-induced bone destruction, we developed a murine model of osteomyelitis. Micro-computed tomography of infected femurs revealed that S. aureus triggers profound alterations in bone turnover. The bacterial regulatory locus sae was found to be critical for osteomyelitis pathogenesis, as Sae-regulated factors promote pathologic bone remodeling and intraosseous bacterial survival. Exoproteome analyses revealed the Sae-regulated protease aureolysin as a major determinant of the S. aureus secretome and identified the phenol soluble modulins as aureolysin-degraded, osteolytic peptides that trigger osteoblast cell death and bone destruction. These studies establish a murine model for pathogen-induced bone remodeling, define Sae as critical for osteomyelitis pathogenesis, and identify protease-dependent exoproteome remodeling as a major determinant of the staphylococcal virulence repertoire. PMID:23768499

  15. Pulmonary venous remodeling in COPD-pulmonary hypertension and idiopathic pulmonary arterial hypertension

    DEFF Research Database (Denmark)

    Andersen, Kasper Hasseriis; Andersen, Claus Bøgelund; Gustafsson, Finn


    Pulmonary vascular arterial remodeling is an integral and well-understood component of pulmonary hypertension (PH). In contrast, morphological alterations of pulmonary veins in PH are scarcely described. Explanted lungs (n = 101) from transplant recipients with advanced chronic obstructive...... pulmonary disease (COPD) and idiopathic pulmonary arterial hypertension (IPAH) were analyzed for venous vascular involvement according to a pre-specified, semi-quantitative grading scheme, which categorizes the intensity of venous remodeling in three groups of incremental severity: venous hypertensive (VH......) grade 0 = characterized by an absence of venous vascular remodeling; VH grade 1 = defined by a dominance of either arterialization or intimal fibrosis; and VH grade 2 = a substantial composite of arterialization and intimal fibrosis. Patients were grouped according to clinical and hemodynamic...

  16. Exercise-Induced Cardiac Remodeling: Lessons from Humans, Horses, and Dogs

    Directory of Open Access Journals (Sweden)

    Rob Shave


    Full Text Available Physical activity is dependent upon the cardiovascular system adequately delivering blood to meet the metabolic and thermoregulatory demands of exercise. Animals who regularly exercise therefore require a well-adapted heart to support this delivery. The purpose of this review is to examine cardiac structure, and the potential for exercise-induced cardiac remodeling, in animals that regularly engage in strenuous activity. Specifically, we draw upon the literature that has studied the “athlete’s heart” in humans, horses, and dogs, to enable the reader to compare and contrast cardiac remodeling in these three athletic species. The available literature provides compelling evidence for exercise-induced cardiac remodeling in all three species. However, more work is required to understand the influence of species/breed specific genetics and exercise-related hemodynamics, in order to fully understand the impact of exercise on cardiac structure.

  17. Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts. (United States)

    Word, R Ann; Li, Xiang-Hong; Hnat, Michael; Carrick, Kelley


    The cervix serves as a protective barrier from invading microorganisms and as a structural barrier to delivery of the fetus. Among all biological processes, the phenomenal connective tissue remodeling that occurs in the cervix during and after parturition is unparalleled in scope and magnitude. The process of connective tissue remodeling in the cervix during pregnancy occurs in four stages: softening, ripening, dilation, and repair. Although overlapping in time, each stage is uniquely regulated. Results from studies using serial measurements of cervical length indicate that cervical ripening precedes myometrial contractions of labor by several weeks, suggesting that parturition in women is a process of long duration and that uterine contractions of labor are late events in the parturition process. A clear understanding of the biologic mechanisms that regulate cervical remodeling during pregnancy is needed to influence the preterm birth rate and to develop strategies to prevent preterm dilation of the cervix.

  18. Postoperative spinal alignment remodeling in Lenke 1C scoliosis treated with selective thoracic fusion

    DEFF Research Database (Denmark)

    Wang, Yu; Bünger, Cody; Zhang, Yanqun


    and how spinal alignment remodeling affects spinal balance. METHODS: All adolescent idiopathic scoliosis (AIS) cases surgically treated in our institution between 2002 and 2008 were reviewed. Inclusion criteria were as follows: Lenke 1C scoliosis patients treated with posterior pedicle screw...... after surgery. Although some patients regained spinal balance through postoperative spinal alignment remodeling, 11 patients remained imbalanced at 2-year follow-up. CONCLUSIONS: Selective thoracic fusion is prone to cause leftward spinal imbalance in Lenke 1C scoliosis patients. Postoperative spinal...... alignment remodeling can facilitate recovery of spinal balance in some patients. Postoperative spinal imbalance in Lenke 1C scoliosis patients could be prevented by selecting stable vertebra or the vertebrae above as LIV, checking the balance condition during surgery, or considering ratio criteria when...

  19. Mononuclear Phagocytes Are Dispensable for Cardiac Remodeling in Established Pressure-Overload Heart Failure.

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    Bindiya Patel

    Full Text Available Although cardiac and splenic mononuclear phagocytes (MPs, i.e., monocytes, macrophages and dendritic cells (DCs, are key contributors to cardiac remodeling after myocardial infarction, their role in pressure-overload remodeling is unclear. We tested the hypothesis that these immune cells are required for the progression of remodeling in pressure-overload heart failure (HF, and that MP depletion would ameliorate remodeling.C57BL/6 mice were subjected to transverse aortic constriction (TAC or sham operation, and assessed for alterations in MPs. As compared with sham, TAC mice exhibited expansion of circulating LyC6hi monocytes and pro-inflammatory CD206- cardiac macrophages early (1 w after pressure-overload, prior to significant hypertrophy and systolic dysfunction, with subsequent resolution during chronic HF. In contrast, classical DCs were expanded in the heart in a biphasic manner, with peaks both early, analogous to macrophages, and late (8 w, during established HF. There was no significant expansion of circulating DCs, or Ly6C+ monocytes and DCs in the spleen. Periodic systemic MP depletion from 2 to 16 w after TAC in macrophage Fas-induced apoptosis (MaFIA transgenic mice did not alter cardiac remodeling progression, nor did splenectomy in mice with established HF after TAC. Lastly, adoptive transfer of splenocytes from TAC HF mice into naïve recipients did not induce immediate or long-term cardiac dysfunction in recipient mice.Mononuclear phagocytes populations expand in a phasic manner in the heart during pressure-overload. However, they are dispensable for the progression of remodeling and failure once significant hypertrophy is evident and blood monocytosis has normalized.

  20. TRPV1 attenuates intracranial arteriole remodeling through inhibiting VSMC phenotypic modulation in hypertension. (United States)

    Zhang, Ming-Jie; Liu, Yun; Hu, Zi-Cheng; Zhou, Yi; Pi, Yan; Guo, Lu; Wang, Xu; Chen, Xue; Li, Jing-Cheng; Zhang, Li-Li


    The phenotypic modulation of contractile vascular smooth muscle cell (VSMC) is widely accepted as the pivotal process in the arterial remodeling induced by hypertension. This study aimed to investigate the potential role of transient receptor potential vanilloid type 1 (TRPV1) on regulating VSMC plasticity and intracranial arteriole remodeling in hypertension. Spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats and TRPV1-/- mice on a C57BL/6J background were used. By microscopic observation of the histopathological sections of vessels from hypertensive SHR and age-matched normotensive WKY control rats, we found that hypertension induced arterial remodeling. Decreased α-smooth muscle actin (α-SMA) and SM22α while increased osteopontin (OPN) were observed in aorta and VSMCs derived from SHR compared with those in WKY, and VSMCs derived from SHR upregulated inflammatory factors. TRPV1 activation by capsaicin significantly increased expression of α-SMA and SM22α, reduced expression of OPN, retarded proliferative and migratory capacities and inhibited inflammatory status in VSMCs from SHR, which was counteracted by TRPV1 antagonist 5'-iodoresiniferatoxin (iRTX) combined with capsaicin. TRPV1 activation by capsaicin ameliorated intracranial arteriole remodeling in SHR and deoxycorticosterone acetate (DOCA)-salt hypertensive mice. However, the attenuation of arteriole remodeling by capsaicin was not observed in TRPV1-/- mice. Furthermore, TRPV1 activation significantly decreased the activity of PI3K and phosphorylation level of Akt in SHR-derived VSMCs. Taken together, we provide evidence that TRPV1 activation by capsaicin attenuates intracranial arteriole remodeling through inhibiting VSMC phenotypic modulation during hypertension, which may be at least partly attributed to the suppression PI3K/Akt signaling pathway. These findings highlight the prospect of TRPV1 in prevention and treatment of hypertension.

  1. Static stretch induces active morphological remodeling and functional impairment of alveolar epithelial cells. (United States)

    Ren, Yanhong; Zhan, Qingyuan; Hu, Qinghua; Sun, Bing; Yang, Chun; Wang, Chen


    Static stretch is frequently observed in the lung. Both static stretch and cyclic stretch can induce cell death and Na(+)/K(+)-ATPase trafficking, but stretch-induced alveolar epithelial cell (AEC) functions are much less responsive to static than to cyclic stretch. AEC remodeling under static stretch may be partly explained. The aim of this study was to explore the AEC remodeling and functional changes under static stretch conditions. We used A549 cells as a model of AEC type II cells. We assessed F-actin content and cell viability by fluorescence staining at various static-stretch magnitudes and time points. Specifically, we used scanning electron microscopy to explore the possible biological mechanisms used by A549 cells to 'escape' static-stretch-induced injury. Finally, we measured choline cytidylyltransferase-alpha (CCT alpha) mRNA and protein by real-time PCR and Western blot to evaluate cellular secretory function. The results showed that the magnitude of static stretch was the primary determinant of static-stretch-induced cell death and cytoskeleton organization, but an extended duration of high static deformation/stretch (37% change in surface area) had no cumulative effects on cell death and cytoskeleton organization. AEC remodeling (expansion-contraction-reexpansion) under static stretch conditions may explain this interesting phenomenon partly. After cell remodeling, CCT alpha expression in A549 cells was influenced not only by stretch magnitude but also by stretch time. Under static stretch conditions, A549 cells undergo morphological and functional changes. They can survive stress failure from overstretching by remodeling their body to 'escape' the injury. During this complex course of remodeling, cellular function was partly damaged. (c) 2009 S. Karger AG, Basel.

  2. Remodeling of adipose tissue at experimental diabetes mellitus

    Directory of Open Access Journals (Sweden)

    O. A. Konovalova


    Full Text Available Introduction Diabetes mellitus (DM type 1 is chronіc disease whith progressive selective destruction of β- cells pancreatic islets (of Langerhans and whith development of absolute insulin failure. Active immune mechanisms take part in pathogenesis of this disease. Recently many publication appeared which report about the role of adipose tissue. In such way adipose tissue is not only the main metabolic regulator and endocrine organ synthesizing more than 30 regulatory proteins- adipokines, but it is one of the organs of immune system. Dysregulation of adipose tissue leads to morphological restructuring- remodeling of adipocytes, and the development of inflammation of adipose tissue in its turn is integral component of progression of many diseases. The aim of research The aim of this study was to investigate the morphological and functional state of parapancreatic fibre adipocytes in male Wistar rats in experimental diabetes mellitus. Materials and methods The study has been carried out on 20 male Wistar rats with weight 115-135 g. The animals were divided into 2 groups. The control group, which were injected 0,5 ml 0,1 М citrate buffer intraperitoneally (1group. Rats with 7 day experimental streptozotocin-induced diabetes mellitus were in the 2nd group. Adipose tissue was examined on the seventh day. For histological examination sections were colored with haematoxylin and eosin. Images were taken by using a fluorescence microscope PrimoStar(ZEISS,Germany with a computer-assisted video system AxioCam 5c (ZEISS,Germany including the NIH-Image software (NIH Image version 1·46. All statistical analyses were performed using EXCEL MS Office 2010 (Microsoft Corp., USA, STATISTICA 6.0 (Stat-Soft, 2001 software. Results were expressed as mean values ± SEM. Differences were considered statistically significant if the p value was <0.05. Results Injection of streptozotocin to experimental animals led to the development of experimental diabetes mellitus


    Directory of Open Access Journals (Sweden)

    Rodica TÖRÖK – OANCE


    Full Text Available Although bones seem inert, however, through the remodelling process, they constantly go through destruction and creation of bone tissue in relation with the mechanical forces that act on them. Bone mechanotransduction intervenes in the perception of the mechanical tensions that occur in the bone as a result of the action of various exterior mechanical forces and in their transformation in biochemical signals, so that the bone can react adequately. The present paper synthesizes recent aspects regarding mechanotransduction and bone remodelling, as well as the relation between them, both for the normal bone and for some pathological situations.

  4. Circulating mediators of bone remodeling in psoriatic arthritis: implications for disordered osteoclastogenesis and bone erosion


    Dalbeth, Nicola; Pool, Bregina; Smith, Timothy; Callon, Karen E.; Lobo, Maria; Taylor, William J.; Jones, Peter B; Cornish, Jillian; McQueen, Fiona M


    Introduction Diverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of patients with PsA. Methods Patients with PsA (n = 38), with psoriasis (n = 10), and healthy controls (n = 12) were studied. Serum was obtained for testing of Dikkopf-1 (Dkk-1), ...

  5. Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling

    DEFF Research Database (Denmark)

    Hansen, N. U. B.; Willumsen, N.; Bülow Sand, Jannie Marie


    Objectives Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competitive...... performance, and in relevant disease cohorts. The developed ELISA was applied for the assessment of type VIII collagen in serum from patients diagnosed with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and various cancers. Results The C8-C ELISA was technically stable...

  6. Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy

    DEFF Research Database (Denmark)

    Ito, Hiromu; Koefoed, Mette; Tiyapatanaputi, Prarop


    Structural allograft healing is limited because of a lack of vascularization and remodeling. To study this we developed a mouse model that recapitulates the clinical aspects of live autograft and processed allograft healing. Gene expression analyses showed that there is a substantial decrease...... in the genes encoding RANKL and VEGF during allograft healing. Loss-of-function studies showed that both factors are required for autograft healing. To determine whether addition of these signals could stimulate allograft vascularization and remodeling, we developed a new approach in which rAAV can be freeze...

  7. Analysis of site-specific N-glycan remodeling in the endoplasmic reticulum and the Golgi (United States)

    Hang, Ivan; Lin, Chia-wei; Grant, Oliver C; Fleurkens, Susanna; Villiger, Thomas K; Soos, Miroslav; Morbidelli, Massimo; Woods, Robert J; Gauss, Robert; Aebi, Markus


    The hallmark of N-linked protein glycosylation is the generation of diverse glycan structures in the secretory pathway. Dynamic, non-template-driven processes of N-glycan remodeling in the endoplasmic reticulum and the Golgi provide the cellular setting for structural diversity. We applied newly developed mass spectrometry-based analytics to quantify site-specific N-glycan remodeling of the model protein Pdi1p expressed in insect cells. Molecular dynamics simulation, mutational analysis, kinetic studies of in vitro processing events and glycan flux analysis supported the defining role of the protein in N-glycan processing. PMID:26240167

  8. Remodeling Mitral Annuloplasty Ring Concept with Preserved Dynamics of Annular Height

    DEFF Research Database (Denmark)

    Skov, Søren N; Røpcke, Diana M; Tjørnild, Marcell J


    . The change and maximum value of the annular height were maintained for the novel ring but were significantly decreased for the rigid and semi-rigid rings compared with the 'no-ring' group. Mitral annular force measurements confirmed that the overall remodeling capacity of the novel ring was comparable...... with the conventional ring groups, and significantly higher in the septal-lateral direction compared to the semi-rigid ring. CONCLUSIONS: In-vivo geometry and force measurements indicated that the intended design features of the new device were successfully provided. The novel ring concept with remodeling properties...

  9. Genome-Wide Mapping Targets of the Metazoan Chromatin Remodeling Factor NURF Reveals Nucleosome Remodeling at Enhancers, Core Promoters and Gene Insulators.

    Directory of Open Access Journals (Sweden)

    So Yeon Kwon


    Full Text Available NURF is a conserved higher eukaryotic ISWI-containing chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding. By sliding nucleosomes, NURF is able to alter chromatin dynamics to control transcription and genome organization. Previous biochemical and genetic analysis of the specificity-subunit of Drosophila NURF (Nurf301/Enhancer of Bithorax (E(bx has defined NURF as a critical regulator of homeotic, heat-shock and steroid-responsive gene transcription. It has been speculated that NURF controls pathway specific transcription by co-operating with sequence-specific transcription factors to remodel chromatin at dedicated enhancers. However, conclusive in vivo demonstration of this is lacking and precise regulatory elements targeted by NURF are poorly defined. To address this, we have generated a comprehensive map of in vivo NURF activity, using MNase-sequencing to determine at base pair resolution NURF target nucleosomes, and ChIP-sequencing to define sites of NURF recruitment. Our data show that, besides anticipated roles at enhancers, NURF interacts physically and functionally with the TRF2/DREF basal transcription factor to organize nucleosomes downstream of active promoters. Moreover, we detect NURF remodeling and recruitment at distal insulator sites, where NURF functionally interacts with and co-localizes with DREF and insulator proteins including CP190 to establish nucleosome-depleted domains. This insulator function of NURF is most apparent at subclasses of insulators that mark the boundaries of chromatin domains, where multiple insulator proteins co-associate. By visualizing the complete repertoire of in vivo NURF chromatin targets, our data provide new insights into how chromatin remodeling can control genome organization and regulatory interactions.

  10. Calpain inhibition prevents pacing-induced cellular remodeling in a HL-1 myocyte model for atrial fibrillation

    NARCIS (Netherlands)

    Brundel, BJJM; Kampinga, HH; Henning, RH


    Objective: Atrial fibrillation (AF) is a progressive disease. Previously, clinical and animal experimental studies in AF revealed a variety of myocyte remodeling processes including L-type Ca(2+) channel reduction and structural changes, which finally result in electrical remodeling and contractile

  11. Age-related Ventricular Remodeling is an Independent Risk for Heart Failure Symptoms in Subjects With Preserved Systolic Function

    Directory of Open Access Journals (Sweden)

    Chung-Lieh Hung


    Conclusion: Cardiac structure, function, and various ventricular remodeling patterns were age-related. Such remodeling process is not only associated with a higher incidence of cardiovascular morbidities but also more likely to develop HF symptoms, which are independent of clinical variables and LV mass.

  12. In vivo micro-CT assessment of airway remodeling in a flexible OVA-sensitized murine model of asthma.

    Directory of Open Access Journals (Sweden)

    Mathieu Lederlin

    Full Text Available Airway remodeling is a major pathological feature of asthma. Up to now, its quantification still requires invasive methods. In this study, we aimed at determining whether in vivo micro-computed tomography (micro-CT is able to demonstrate allergen-induced airway remodeling in a flexible mouse model of asthma. Sixty Balb/c mice were challenged intranasally with ovalbumin or saline at 3 different endpoints (Days 35, 75, and 110. All mice underwent plethysmography at baseline and just prior to respiratory-gated micro-CT. Mice were then sacrificed to assess bronchoalveolar lavage and lung histology. From micro-CT images (voxel size = 46×46×46 µm, the numerical values of total lung attenuation, peribronchial attenuation (PBA, and PBA normalized by total lung attenuation were extracted. Each parameter was compared between OVA and control mice and correlation coefficients were calculated between micro-CT and histological data. As compared to control animals, ovalbumin-sensitized mice exhibited inflammation alone (Day 35, remodeling alone (Day 110 or both inflammation and remodeling (Day 75. Normalized PBA was significantly greater in mice exhibiting bronchial remodeling either alone or in combination with inflammation. Normalized PBA correlated with various remodeling markers such as bronchial smooth muscle size or peribronchial fibrosis. These findings suggest that micro-CT may help monitor remodeling non-invasively in asthmatic mice when testing new drugs targeting airway remodeling in pre-clinical studies.

  13. A Bone Remodelling Model Based on Generalised Thermodynamic Potentials and Optimisation Applied to a Trabecula with Cyclic Loading

    Directory of Open Access Journals (Sweden)

    F. V. Tormena


    Full Text Available Background: Bone diseases caused by an imbalance of bone turnover represent a major public health concern worldwide. Studies involving bone remodelling mechanisms can assist in the treatment of osteoporosis, osteopenia and in cases of fractures. In recent decades several authors have developed bone remodelling models.

  14. Postoperative Reverse Remodeling and Symptomatic Improvement in Normal-Flow Low-Gradient Aortic Stenosis After Aortic Valve Replacement

    DEFF Research Database (Denmark)

    Carter-Storch, Rasmus; Møller, Jacob E; Christensen, Nicolaj L


    . CONCLUSIONS: Patients with NFLG had less severe AS and LV remodeling than patients with normal-flow high-gradient. Furthermore, NFLG patients experienced less reverse remodeling but the same symptomatic benefit. CLINICAL TRIAL REGISTRATION: URL: Unique identifier: NCT02316587....

  15. Leadership, New Public Management and the Re-Modelling and Regulation of Teacher Identities (United States)

    Hall, David; Gunter, Helen; Bragg, Joanna


    This article examines the rapidly shifting relationship between teachers and the state and efforts to re-model teacher identities within the wider context of public sector modernization and the New Public Management. The construction and development of officially authorized and normative discursive practices relating to leadership and the…

  16. Tangshen Formula Attenuates Colonic Structure Remodeling in Type 2 Diabetic Rats

    DEFF Research Database (Denmark)

    Chen, Pengmin; Zhao, Jingbo; Zhang, Haojun


    Aim. This study investigated the effect and mechanism of the Chinese herbal medicine Tangshen Formula (TSF) on GI structure remodeling in the rat model of diabetes. Methods. Type 2 diabetic rats were used. Wet weight per unit length, layer thicknesses, levels of collagens I and III, nuclear factor...

  17. Airway Microbiota Determines Innate Cell Inflammatory or Tissue Remodeling Profiles in Lung Transplantation. (United States)

    Bernasconi, Eric; Pattaroni, Céline; Koutsokera, Angela; Pison, Christophe; Kessler, Romain; Benden, Christian; Soccal, Paola M; Magnan, Antoine; Aubert, John-David; Marsland, Benjamin J; Nicod, Laurent P


    In lung transplant recipients, long-term graft survival relies on the control of inflammation and tissue remodeling to maintain graft functionality and avoid chronic lung allograft dysfunction. Although advances in clinical practice have improved transplant success, the mechanisms by which the balance between inflammation and remodeling is maintained are largely unknown. To assess whether host-microbe interactions in the transplanted lung determine the immunologic tone of the airways, and consequently could impact graft survival. Microbiota DNA and host total RNA were isolated from 203 bronchoalveolar lavages obtained from 112 patients post-lung transplantation. Microbiota composition was determined using 16S ribosomal RNA analysis, and expression of a set of genes involved in prototypic macrophage functions was quantified using real-time quantitative polymerase chain reaction. We show that the characteristics of the pulmonary microbiota aligned with distinct innate cell gene expression profiles. Although a nonpolarized activation was associated with bacterial communities consisting of a balance between proinflammatory (e.g., Staphylococcus and Pseudomonas) and low stimulatory (e.g., Prevotella and Streptococcus) bacteria, "inflammatory" and "remodeling" profiles were linked to bacterial dysbiosis. Mechanistic assays provided direct evidence that bacterial dysbiosis could lead to inflammatory or remodeling profiles in macrophages, whereas a balanced microbial community maintained homeostasis. The crosstalk between bacterial communities and innate immune cells potentially determines the function of the transplanted lung offering novel pathways for intervention strategies.

  18. The Relationship of Myocardial Collagen Metabolism and Reverse Remodeling after Cardiac Resynchronization Therapy

    Directory of Open Access Journals (Sweden)

    Petrovic Ivana


    Full Text Available Background: In the majority of patients with a wide QRS complex and heart failure resistant to optimal medical therapy, cardiac resynchronization therapy (CRT leads to rever se ventricular remodeling and possibly to changes in cardiac collagen synthesis and degradation. We investigated the relationship of biomarkers of myocardial collagen meta bolism and volumetric response to CRT.

  19. Premature loss of bone remodeling compartment canopies is associated with deficient bone formation

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Søe, Kent


    support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces...

  20. Functional, Cellular, and Molecular Remodeling of the Heart under Influence of Oxidative Cigarette Tobacco Smoke

    Directory of Open Access Journals (Sweden)

    Abdullah Kaplan


    Full Text Available Passive and active chronic cigarette smoking (CS remains an international epidemic and a key risk factor for cardiovascular disease (CVD development. CS-induced cardiac damage is divided into two major and interchangeable mechanisms: (1 direct adverse effects on the myocardium causing smoking cardiomyopathy and (2 indirect effects on the myocardium by fueling comorbidities such as atherosclerotic syndromes and hypertension that eventually damage and remodel the heart. To date, our understanding of cardiac remodeling following acute and chronic smoking exposure is not well elucidated. This manuscript presents for the first time the RIMD (oxidative stress (R, inflammation (I, metabolic impairment (M, and cell death (D detrimental cycle concept as a major player in CS-induced CVD risks and direct cardiac injury. Breakthroughs and latest findings in the field with respect to structural, functional, cellular, and molecular cardiac remodeling following chronic smoking exposure are summarized. This review also touches the genetics/epigenetics of smoking as well as the smoker’s paradox and highlights the most currently prominent pharmacological venues to mitigate CS-induced adverse cardiac remodeling.

  1. Synaptic Remodeling Generates Synchronous Oscillations in the Degenerated Outer Mouse Retina

    Directory of Open Access Journals (Sweden)

    Wadood eHaq


    Full Text Available During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs establish contacts with remnant cone photoreceptors (cones as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca2+ imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs, we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from HCs. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells.

  2. The Impact of Workforce Remodelling on Change Management and Working Practices in English Primary Schools (United States)

    Hammersley-Fletcher, Linda


    Reports of a recruitment and retention crisis amongst teachers in England led the government to develop a Workforce Remodelling strategy for schools. This involved change at both a legislative level, removing administrative tasks from teachers and ensuring all teaching staff had 10% off-timetable for planning, preparation and assessment (PPA)…

  3. Arrhythmogenesis in the remodeled heart : the role of spatially dispersed Cx43 expression

    NARCIS (Netherlands)

    Boulaksil, M.


    The heart is able to adapt to new, often pathologic, conditions, so-called cardiac remodeling. Although initially adequate, these adaptations could can become maladaptive over time. One of the adaptations of the heart during pathology is ventricular hypertrophy, which may go hand in hand with an

  4. Calcium channel blockade prevents pressure-dependent inward remodeling in isolated subendocardial resistance vessels

    NARCIS (Netherlands)

    O. Sorop (Oana); E.N.T.P. Bakker (Erik ); A. Pistea (Adrian); J.A. Spaan (Jos Ae); E. VanBavel (Ed)


    textabstractThe capacity for myocardial perfusion depends on the structure of the coronary microvascular bed. Coronary microvessels may adapt their structure to various stimuli. We tested whether the local pressure profile affects tone and remodeling of porcine coronary microvessels. Subendocardial

  5. Modalities for visualization of cortical bone remodeling: the past, present and near future

    Directory of Open Access Journals (Sweden)

    Kimberly Dawn Harrison


    Full Text Available Bone’s ability to respond to load-related phenomena and repair microdamage is achieved through the remodeling process which renews bone by activating groups of cells known as Basic Multicellular Units (BMUs. The products of BMUs, secondary osteons, have been extensively studied via classic two-dimensional (2D techniques which have provided a wealth of information on how histomorphology relates to skeletal structure and function. Remodeling is critical in maintaining healthy bone tissue; however, in osteoporotic bone imbalanced resorption results in increased bone fragility and fracture. With increasing life expectancy, such degenerative bone diseases are a growing concern. The three-dimensional (3D morphology of BMUs and their correlation to function, however, are not well characterized and little is known about the specific mechanisms that initiate and regulate their activity within cortical bone. We believe a key limitation has been the lack 3D information about BMU morphology and activity. Thus, this paper reviews methodologies for 3D investigation of cortical bone remodeling and, specifically, structures associated with BMU activity (resorption spaces and the structures they create (secondary osteons, spanning from histology to modern ex vivo imaging modalities, culminating with the growing potential of in vivo imaging. This collection of papers focuses on the theme of putting the why back into bone archytecture. Remodeling is one of two mechanisms how bone structure is dynamically modified and thus an improved 3D understanding of this fundamental process is crucial to ultimately understanding the why.

  6. Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies?

    Directory of Open Access Journals (Sweden)

    Brian R. Weil


    Full Text Available Atrial fibrillation (AF is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets.

  7. Delayed exercise promotes remodeling in sub-rupture fatigue damaged tendons. (United States)

    Bell, R; Boniello, M R; Gendron, N R; Flatow, E L; Andarawis-Puri, N


    Tendinopathy is a common musculoskeletal injury whose treatment is limited by ineffective therapeutic interventions. Previously we have shown that tendons ineffectively repair early sub-rupture fatigue damage. In contrast, physiological exercise has been shown to promote remodeling of healthy tendons but its utility as a therapeutic to promote repair of fatigue damaged tendons remains unknown. Therefore, the objective of this study was to assess the utility of exercise initiated 1 and 14 days after onset of fatigue damage to promote structural repair in fatigue damaged tendons. We hypothesized that exercise initiated 14 days after fatigue loading would promote remodeling as indicated by a decrease in area of collagen matrix damage, increased procollagen I and decorin, while decreasing proteins indicative of tendinopathy. Rats engaged in 6-week exercise for 30 min/day or 60 min/day starting 1 or 14 days after fatigue loading. Initiating exercise 1-day after onset of fatigue injury led to exacerbation of matrix damage, particularly at the tendon insertion. Initiating exercise 14 days after onset of fatigue injury led to remodeling of damaged regions in the midsubstance and collagen synthesis at the insertion. Physiological exercise applied after the initial biological response to injury has dampened can potentially promote remodeling of damaged tendons. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  8. Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium. (United States)

    Weber, Karl T; Weglicki, William B; Simpson, Robert U


    Hypertension and heart failure are worldwide health problems of ever-increasing proportions. A failure of the heart, during either systolic and/or diastolic phases of the cardiac cycle, has its origins rooted in an adverse structural, biochemical, and molecular remodelling of myocardium that involves its cellular constituents, extracellular matrix, and intramural coronary vasculature. Herein we focus on the pathogenic role of a dyshomeostasis of several macro- (i.e. Ca(2+) and Mg(2+)) and micronutrients (i.e. Zn(2+), Se(2+), and vitamin D) in contributing to adverse remodelling of the myocardium and its failure as a pulsatile muscular pump. An improved understanding of how these macro- and micronutrients account for the causes and consequences of adverse myocardial remodelling carries with it the potential of identifying new biomarkers predictive of risk, onset and progression, and response to intervention(s), which could be monitored non-invasively and serially over time. Moreover, such incremental knowledge will serve as the underpinning to the development of novel strategies aimed at preventing and/or regressing the ongoing adverse remodelling of myocardium. The time is at hand to recognize the importance of macro- and micronutrient dyshomeostasis in the evaluation and management of hypertension and heart failure.

  9. A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis (United States)

    Kuleesha, Yadav; Puah, Wee Choo; Wasser, Martin


    Genes controlling muscle size and survival play important roles in muscle wasting diseases. In Drosophila melanogaster metamorphosis, larval abdominal muscles undergo two developmental fates. While a doomed population is eliminated by cell death, another persistent group is remodelled and survives into adulthood. To identify and characterize genes involved in the development of remodelled muscles, we devised a workflow consisting of in vivo imaging, targeted gene perturbation and quantitative image analysis. We show that inhibition of TOR signalling and activation of autophagy promote developmental muscle atrophy in early, while TOR and yorkie activation are required for muscle growth in late pupation. We discovered changes in the localization of myonuclei during remodelling that involve anti-polar migration leading to central clustering followed by polar migration resulting in localization along the midline. We demonstrate that the Cathepsin L orthologue Cp1 is required for myonuclear clustering in mid, while autophagy contributes to central positioning of nuclei in late metamorphosis. In conclusion, studying muscle remodelling in metamorphosis can provide new insights into the cell biology of muscle wasting. PMID:26998322

  10. Instrumental and laboratory assessment of stressful remodelling processes in bone tissue at total hip replacement

    Directory of Open Access Journals (Sweden)

    E.V. Karjakina


    Full Text Available Research objective is to estimate stressful remodelling features of bone tissue according to the densitometry data and to the level of biochemical markers of bone resorption and formation in total hip replacement (THR. Bone tissue mineral density (BTMD, condition of calcium-phosphoric metabolism and biochemical markers of bone formation (osteocalcin and bone isoenzyme of alkaline phosphatase and resorption (С-terminal bodypeptide of the I type collagen have been determined in 52 patients with coxarthrosis of ll-lll stages with marked joint dysfunction before and after THR. The control group included 24 donors. The data were considered to be reliable when the probability index was р<0,05. The reliable (р<0,05 change of BTMD was determined only in 3-6 months after the operation, whereas the change of biochemical markers of remodeling had already been done after 1,5-3 months, allowing to define the group of patients with obvious negative bone balance: strong predominance of resorption processes without compensation of the subsequent adequate osteogenesis, that subsequently could lead to significant bone tissue deficiency in the area adjacent to the endoprosthesis. Changes of indices of calcium-phosphoric metabolism were not certain during the investigation term. ln conclusion it is to state that biochemical markers of remodeling in comparison with BTMD allow to estimate objectively features of adaptive bone tissue remodeling after THR in earlier periods and to define group of patients with sharp intensification of metabolism and obvious negative bone balance

  11. Inflammatory Regulation of Valvular Remodeling: The Good(?, the Bad, and the Ugly

    Directory of Open Access Journals (Sweden)

    Gretchen J. Mahler


    Full Text Available Heart valve disease is unique in that it affects both the very young and very old, and does not discriminate by financial affluence, social stratus, or global location. Research over the past decade has transformed our understanding of heart valve cell biology, yet still more remains unclear regarding how these cells respond and adapt to their local microenvironment. Recent studies have identified inflammatory signaling at nearly every point in the life cycle of heart valves, yet its role at each stage is unclear. While the vast majority of evidence points to inflammation as mediating pathological valve remodeling and eventual destruction, some studies suggest inflammation may provide key signals guiding transient adaptive remodeling. Though the mechanisms are far from clear, inflammatory signaling may be a previously unrecognized ally in the quest for controlled rapid tissue remodeling, a key requirement for regenerative medicine approaches for heart valve disease. This paper summarizes the current state of knowledge regarding inflammatory mediation of heart valve remodeling and suggests key questions moving forward.

  12. Synaptic degeneration and remodelling after fast kindling of the olfactory bulb

    DEFF Research Database (Denmark)

    Woldbye, D P; Bolwig, T G; Kragh, J


    in the basolateral amygdala and dentate gyrus, suggesting that these regions may be functionally altered during the kindling process. In the piriform cortex and dentate gyrus increased NCAM/D3(SNAP-25) ratios found ipsilaterally at seven days after kindling probably reflect an elevated rate of synaptic remodelling...

  13. Chronic alcoholism and bone remodeling processes: Caveats and considerations for the forensic anthropologist. (United States)

    Michael, Amy R; Bengtson, Jennifer D


    Clinical literature provides substantial information on the effects of chronic alcohol abuse on bone remodeling and related skeletal disease processes. This biomedical information is seldom considered in detail by forensic anthropologists, who often rely on normative macroscopic models of bone remodeling and traditional macroscopic age estimation methods in the creation of biological profiles. The case study presented here considers the ways that alcoholism disrupts normal bone remodeling processes, thus skewing estimations of age-at-death. Alcoholism affects bone macroscopically, resulting in a porous appearance and an older estimation of age, while simultaneously inhibiting osteoblastic activity and resulting in a younger microscopic appearance. Forensic anthropologists must also be cognizant of pathological remodeling stemming from alcoholism in cases where trauma analysis is critical to the reconstruction of events leading up to death, as fracture healing rates can be affected. Beyond the case study, we also consider how forensic anthropologists and practitioners can recognize and account for osteological signatures of alcoholism in medico-legal contexts. In order to best estimate age at death, a combined macroscopic and microscopic approach should be employed whenever possible alcohol and drug abuse is known or suspected. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  14. A mechanism for arteriolar remodeling based on maintenance of smooth muscle cell activation

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian Brings; Mulvany, Michael John; Holstein-Rathlou, N.-H.


    activation. We present a simple dynamic model and show that structural remodeling of the vessel radius by rearrangement of the wall material around a lumen of a different diameter and driven by differences in SMC activation can lead to vascular structures similar to those observed experimentally under...

  15. Continuous lactation effects on mammary remodeling during late gestation and lactation in dairy goats

    DEFF Research Database (Denmark)

    Safayi, Sina; Theil, Peter Kappel; Hou, Lei


    The present study aimed to 1) elucidate whether continuous milking during late gestation in dairy goats negatively affects mammary remodeling and hence milk production in the subsequent lactation, and 2) identify the regulatory factors responsible for changes in cell turnover and angiogenesis...

  16. Stem cell-based growth, regeneration, and remodeling of the planarian intestine (United States)

    Forsthoefel, David J.; Park, Amanda E.; Newmark, Phillip A.


    Although some animals are capable of regenerating organs, the mechanisms by which this is achieved are poorly understood. In planarians, pluripotent somatic stem cells called neoblasts supply new cells for growth, replenish tissues in response to cellular turnover, and regenerate tissues after injury. For most tissues and organs, however, the spatiotemporal dynamics of stem cell differentiation and the fate of tissue that existed prior to injury have not been characterized systematically. Utilizing in vivo imaging and bromodeoxyuridine pulse-chase experiments, we have analyzed growth and regeneration of the planarian intestine, the organ responsible for digestion and nutrient distribution. During growth, we observe that new gut branches are added along the entire anteroposterior axis. We find that new enterocytes differentiate throughout the intestine rather than in specific growth zones, suggesting that branching morphogenesis is achieved primarily by remodeling of differentiated intestinal tissues. During regeneration, we also demonstrate a previously unappreciated degree of intestinal remodeling, in which pre-existing posterior gut tissue contributes extensively to the newly formed anterior gut, and vice versa. By contrast to growing animals, differentiation of new intestinal cells occurs at preferential locations, including within newly generated tissue (the blastema), and along pre-existing intestinal branches undergoing remodeling. Our results indicate that growth and regeneration of the planarian intestine are achieved by coordinated differentiation of stem cells and the remodeling of pre-existing tissues. Elucidation of the mechanisms by which these processes are integrated will be critical for understanding organogenesis in a post-embryonic context. PMID:21664348

  17. The Remodeling Process: A Grounded Theory Study of Perceptions of Treatment among Adult Male Incest Offenders. (United States)

    Scheela, Rochelle A.


    Conducted grounded theory study to explore incest offender perceptions of treatment to generate explanatory theory of sexual abuse treatment process. Findings from theoretical sampling of 20 adult male incest offenders revealed that offenders felt remodeling process occurred as they faced discovery of their abuse and went through treatment.…

  18. Electrophysiologic Remodeling of the Left Ventricle in Pressure Overload-Induced Right Ventricular Failure

    NARCIS (Netherlands)

    Hardziyenka, Maxim; Campian, Maria E.; Verkerk, Arie O.; Surie, Sulaiman; van Ginneken, Antoni C. G.; Hakim, Sara; Linnenbank, André C.; de Bruin-Bon, Rianne H. A. C. M.; Beekman, Leander; van der Plas, Mart N.; Remme, Carol A.; van Veen, Toon A. B.; Bresser, Paul; de Bakker, Jacques M. T.; Tan, Hanno L.


    Objectives The purpose of this study was to analyze the electrophysiologic remodeling of the atrophic left ventricle (LV) in right ventricular (RV) failure (RVF) after RV pressure overload. Background The LV in pressure-induced RVF develops dysfunction, reduction in mass, and altered gene

  19. Compact tomato seedlings and plants upon overexpression of a tomato chromatin remodelling ATPase gene

    NARCIS (Netherlands)

    Folta, A.; Bargsten, J.W.; Bisseling, T.; Nap, J.P.H.; Mlynarova, L.


    Control of plant growth is an important aspect of crop productivity and yield in agriculture. Overexpression of the AtCHR12/23 genes in Arabidopsis thaliana reduced growth habit without other morphological changes. These two genes encode Snf2 chromatin remodelling ATPases. Here, we translate this

  20. Proarrhythmic electrical remodelling is associated with increased beat-to-beat variability of repolarisation

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard; Oros, Avram; Schoenmakers, Marieke


    Acquired long-QT syndrome in combination with increased beat-to-beat variability of repolarisation duration (BVR) is associated with lethal torsades de pointes arrhythmias (TdP) in dogs with remodelled heart after atrioventricular block (AVB). We evaluated the relative contributions of bradycardi...

  1. Adaptive bone-remodeling theory applied to prosthetic-design analysis

    NARCIS (Netherlands)

    R. Huiskes (Rik); H.H. Weinans (Harrie); H.J. Grootenboer; M. Dalstra; B. Fudala; T.J. Slooff


    textabstractThe subject of this article is the development and application of computer-simulation methods to predict stress-related adaptive bone remodeling, in accordance with 'Wolff's Law'. These models are based on the Finite Element Method (FEM) in combination with numerical formulations of

  2. Characterization Report for the Demolition and Remodel of B151 Rooms 1318, 1322 and 1326

    Energy Technology Data Exchange (ETDEWEB)

    Sexton, Jenna L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Won, Geoffrey [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)


    In support of a remodel for rooms 1318, 1322, and 1326 in building 151, the Environmental Safety and Health (ES&H) team has worked to develop a detailed characterization of contaminants in each room. This report serves as a summary of the results for all radioactive material and Industrial Hygiene (IH) metals sampling performed of accessible areas.

  3. Ubuntu-Praxis: Re-Modelling the Balanced Scorecard Model at a University, an Afrocentric Perspective (United States)

    Ndoda, Gladys Ruvimbo; Sikwila, Mike Nyamazana


    The authors design the innovation and learning perspective of the Balanced Scorecard (BSC) of "Ubuntu and client service charter nexus." This article borrows and advances the research carried out by Khomba, Vermaak and Gouws (2011). The point of departure is on praxis of ubuntu/unhu as a holistic approach in the re-modelling of the BSC…

  4. Rhinovirus infection induces expression of airway remodelling factors in vitro and in vivo

    NARCIS (Netherlands)

    Kuo, Curtis; Lim, Sam; King, Nicholas J C; Bartlett, Nathan W; Walton, Ross P; Zhu, Jie; Glanville, Nicholas; Aniscenko, Julia; Johnston, Sebastian L; Burgess, Janette K; Black, Judith L; Oliver, Brian G

    BACKGROUND AND OBJECTIVE: A hallmark of asthma is airway remodelling, which includes increased deposition of extracellular matrix (ECM) protein. Viral infections may promote the development of asthma and are the most common causes of asthma exacerbations. We evaluated whether rhinovirus (RV)

  5. Identification of a Remodeled Neo-tendon After Arthroscopic Latarjet Procedure. (United States)

    Smolen, Daniel; Went, Philip; Tomala, Dirk; Sternberg, Christoph; Lafosse, Laurent; Leuzinger, Jan


    To macroscopically, histologically, and radiologically describe a time-dependent remodeling process of a neo-tendon or -ligament in the shoulder after the arthroscopic Latarjet procedure. During follow-up surgery after the arthroscopic Latarjet procedure, 17 shoulders in 16 patients were evaluated for a remodeled tendon-like structure. The mean overall follow-up period was 27.4 months. The mean time between the arthroscopic Latarjet procedure and revision was 11.6 months. All shoulders were evaluated with magnetic resonance imaging, and seven histologic specimens were obtained during revision surgery. A distinct, oriented strand of tissue was found in 16 of 17 shoulders on revision surgery. Postoperative magnetic resonance imaging analyses showed a signal-free, longitudinal tendon-like structure originating at the tip of the acromion, traversing the space of the former subcoracoid bursa to attach in the course of the transposed conjoint tendon or the proximal short head of the biceps. Histologic analysis of seven specimens showed a characteristic timeline of remodeling. A tendon- or ligament-like structure is remodeled between the anterior bottom tip of the acromion and the transposed coracoid process in a time-dependent manner after the arthroscopic Latarjet procedure. Level IV, therapeutic case series. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  6. Passive solar design strategies: Remodeling guidelines for conserving energy at home

    Energy Technology Data Exchange (ETDEWEB)


    The idea of passive solar is simple, but applying it effectively does require information and attention to the details of design and construction. Some passive solar techniques are modest and low-cost, and require only small changes in remodeler's typical practice. At the other end of the spectrum, some passive solar systems can almost eliminate a house's need for purchased heating (and in some cases, cooling) energy -- but probably at a relatively high first cost. In between are a broad range of energy-conserving passive solar techniques. Whether or not they are cost-effective, practical and attractive enough to offer a market advantage to any individual remodeler depends on very specific factors such as local costs, climate, and market characteristics. Passive solar design strategies: Remodeling Guidelines For Conserving Energy At Homes is written to help give remodelers the information they need to make these decisions. Passive Solar Design Strategies is a package in three basic parts: The Guidelines contain information about passive solar techniques and how they work, and provides specific examples of systems which will save various percentages of energy; The Worksheets offer a simple, fill-in-the-blank method to pre-evaluate the performance of a specific design; The Worked Example demonstrates how to complete the worksheets for a typical residence.

  7. Sarcomeric lesions and remodeling proximal to intercalated disks in overload-induced cardiac hypertrophy. (United States)

    Kebir, Sied; Orfanos, Zacharias; Schuld, Julia; Linhart, Markus; Lamberz, Christian; van der Ven, Peter F M; Schrickel, Jan; Kirfel, Gregor; Fürst, Dieter O; Meyer, Rainer


    Pressure overload induces cardiac remodeling involving both the contractile machinery and intercalated disks (IDs). Filamin C (FlnC) and Xin actin-binding repeat-containing proteins (XIRPs) are multi-adapters localizing in IDs of higher vertebrates. Knockout of the gene encoding Xin (Xirp1) in mice leads to a mild cardiac phenotype with ID mislocalization. In order to amplify this phenotype, we performed transverse aortic constriction (TAC) on control and Xirp1-deficient mice. TAC induced similar left ventricular hypertrophy in both genotypes, suggesting that the lack of Xin does not lead to higher susceptibility to cardiac overload. However, in both genotypes, FlnC appeared in "streaming" localizations across multiple sarcomeres proximal to the IDs, suggesting a remodeling response. Furthermore, FlnC-positive areas of remodeling, reminiscent of sarcomeric lesions previously described for skeletal muscles (but so far unreported in the heart), were also observed. These adaptations reflect a similarly strong effect of the pressure induced by TAC in both genotypes. However, 2 weeks post-operation TAC-treated knockout hearts had reduced levels of connexin43 and slightly increased incidents of ventricular tachycardia compared to their wild-type (WT) counterparts. Our findings highlight the FlnC-positive sarcomeric lesions and ID-proximal streaming as general remodeling responses in cardiac overload-induced hypertrophy. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Synaptic remodeling generates synchronous oscillations in the degenerated outer mouse retina (United States)

    Haq, Wadood; Arango-Gonzalez, Blanca; Zrenner, Eberhart; Euler, Thomas; Schubert, Timm


    During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs) establish contacts with remnant cone photoreceptors (cones) as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca2+ imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs), we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from interneurons such as HCs and/or possibly interplexiform cells. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type) cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates) the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells. PMID:25249942

  9. Pro- and anti-inflammatory cytokines in post-infarction left ventricular remodeling. (United States)

    Zarrouk-Mahjoub, S; Zaghdoudi, M; Amira, Z; Chebi, H; Khabouchi, N; Finsterer, J; Mechmeche, R; Ghazouani, E


    Acute myocardial infarction (MI) leads to molecular, structural, geometric and functional changes in the heart during a process known as ventricular remodeling. Myocardial infarction is followed by an inflammatory response in which pro- and anti-inflammatory cytokines play a crucial role, particularly in left ventricular remodeling. This study aimed at evaluating serum concentrations of interleukin-8 (IL8), tumor-necrosis-factor-alpha (TNFα) and interleukin-10 (IL10), pro- and anti-inflammatory cytokines, and at correlating them with left ventricular remodeling as assessed by echocardiographic parameters. In a case-control study 30 MI patients were compared with 30 healthy controls. Serum concentrations of IL8, TNFα and IL10 were measured on day 2 and day 30 post-MI by chemiluminescence immunoassay and correlated with echocardiographic parameters. There was an increase of IL8, and TNFα together with a decrease of IL10 at both time points. IL8 was negatively correlated with the left ventricular end-diastolic diameter (LVEDD) and positively with left ventricular systolic volume. IL10 was negatively correlated with LVEDD and left atrial volume 30days post-MI. The increase of pro-inflammatory cytokines TNFα and IL8 was accompanied by decreased anti-inflammatory IL10. This imbalance between pro- and anti-inflammatory cytokines might contribute to the progression of left ventricular remodeling and may lead to heart failure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Computation of bone remodelling after Duracon knee arthroplasty using a thermodynamic-based model

    Czech Academy of Sciences Publication Activity Database

    Bougherara, H.; Nazgooei, S.; Sayyidmousavi, A.; Maršík, František; Mařík, I.


    Roč. 225, H7 (2011), s. 669-679 ISSN 0954-4119 R&D Projects: GA ČR(CZ) GA106/08/0557 Institutional research plan: CEZ:AV0Z20760514 Keywords : bone remodelling * chemical kinetics * stress shielding Subject RIV: FI - Traumatology, Orthopedics Impact factor: 1.208, year: 2011

  11. Cardiac remodeling following percutaneous mitral valve repair - initial results assessed by cardiovascular magnetic resonance imaging

    DEFF Research Database (Denmark)

    Radunski, U K; Franzen, O; Barmeyer, A


    (CMR) to assess reverse myocardial remodeling in patients after MitraClip implantation. MATERIALS AND METHODS: 12 patients underwent CMR at baseline (BL) before and at 6 months follow-up (FU) after MitraClip implantation. Cine-CMR was performed in short- and long-axes for the assessment of left...

  12. Impact of age, sex and exercise on brachial and popliteal artery remodelling in humans.

    NARCIS (Netherlands)

    Green, D.J.; Swart, A.; Exterkate, A.; Naylor, L.H.; Black, M.A.; Cable, N.T.; Thijssen, D.H.J.


    OBJECTIVE: To examine the impact of age, sex and exercise on wall thickness and remodelling in the popliteal and brachial arteries. METHODS: We compared wall thickness, lumen diameter and wall:lumen ratios in the brachial and popliteal arteries of 15 young (Y, 25.4+/-0.8 yr; 7M 8W) and 16 older

  13. Transcriptional repression of the yeast CHA1 gene requires the chromatin-remodeling complex RSC

    DEFF Research Database (Denmark)

    Moreira, José Manuel Alfonso; Holmberg, S


    In eukaryotes, DNA is packaged into chromatin, a compact structure that must be disrupted when genes are transcribed by RNA polymerase II. For transcription to take place, chromatin is remodeled via nucleosome disruption or displacement, a fundamental transcriptional regulatory mechanism in eukar...

  14. Early exercise training after myocardial infarction prevents contractile but not electrical remodelling or hypertrophy

    NARCIS (Netherlands)

    V. Bito (Virginie); M.C. de Waard (Monique); L. Biesmans (Liesbeth); I. Lenaerts (Ilse); S. Ozdemir (Semir); E.D. van Deel (Elza); Y. Abdel-Mottaleb (Yousra); R. Driesen (Ronald); P. Holemans (Patricia); D.J.G.M. Duncker (Dirk); K.R. Sipido (Karin)


    textabstractAims: Exercise started early after myocardial infarction (MI) improves in vivo cardiac function and myofilament responsiveness to Ca2+. We investigated whether this represents partial or complete reversal of cellular remodelling. Methods and results: Mice with MI following left coronary

  15. Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases

    DEFF Research Database (Denmark)

    Genovese, Federica; Barascuk, Natasha; Larsen, Lise Skakkebæk


    The proteoglycan biglycan (BGN) is involved in collagen fibril assembly and its fragmentation is likely to be associated with collagen turnover during the pathogenesis of diseases which involve dysregulated extracellular matrix remodeling (ECMR), such as rheumatoid arthritis (RA) and liver fibrosis...

  16. Traditional Chinese Medication Qiliqiangxin attenuates cardiac remodeling after acute myocardial infarction in mice

    NARCIS (Netherlands)

    Tao, Lichan; Shen, Sutong; Fu, Siyi; Fang, Hongyi; Wang, Xiuzhi; Das, Saumya; Sluijter, Joost P. G.; Rosenzweig, Anthony; Zhou, Yonglan; Kong, Xiangqing; Xiao, Junjie; Li, Xinli


    In a multicenter randomized double-blind study we demonstrated that Qiliqiangxin (QLQX), a traditional Chinese medicine, had a protective effect in heart failure patients. However, whether and via which mechanism QLQX attenuates cardiac remodeling after acute myocardial infarction (AMI) is still

  17. Berberine Attenuates Vascular Remodeling and Inflammation in a Rat Model of Metabolic Syndrome. (United States)

    Li, Xiao-Xing; Li, Chuan-Bao; Xiao, Jie; Gao, Hai-Qing; Wang, He-Wen; Zhang, Xin-Yu; Zhang, Cheng; Ji, Xiao-Ping


    Berberine is a natural product that shows benefits for metabolic syndrome (MS). However, the effects of berberine on the improvement of vascular inflammation and remodeling in MS remain unclear. This study aimed to investigate whether berberine could prevent vascular remodeling and inflammation in the MS condition. A rat model of MS was established, and MS rats were divided into two groups: MS group without berberine treatment, and MSB group with berberine treatment (each group n-10). Ten normal Wistar rats were used as controls (NC group). Vascular damage was examined by transmission electron microscopy and pathological staining. Compared to the NC group, the secretion of inflammatory factors was increased and the aortic wall thicker in the MS group. The MSB group exhibited decreased secretion of inflammatory factors and improved vascular remodeling, compared to the MS group. In addition, the levels of p38 mitogen-activated protein kinase (p38 MAPK), activating transcription factor 2 (ATF-2) and matrix metalloproteinase 2 (MMP-2) were significantly decreased in the MSB group compared to the MS group. In conclusion, our data show that berberine improves vascular inflammation and remodeling in the MS condition, and this is correlated with the ability of berberine to inhibit p38 MAPK activation, ATF-2 phosphorylation, and MMP-2 expression.

  18. Aortic valve remodelling with Urbanski's technique of separate patches - own experience

    NARCIS (Netherlands)

    Bitner, Miroslaw; Jaszewski, Ryszard; Banys, Andrzej; Jander, Slawomir; Walczak, Andrzej; Ostrowski, Stanislaw; Wojtasik, Leszek

    Background: In 2005 Dr Urbanski described modification of the aortic valve remodelling technique in 20 patients. Since July 2006 we have been using his method. Aim: Evaluation of technical aspects, efficacy and usefulness of this technique based on our results. Material and Methods: 17 patients with

  19. Role of extracellular matrix remodelling in adipose tissue pathophysiology: relevance in the development of obesity. (United States)

    Catalán, V; Gómez-Ambrosi, J; Rodríguez, A; Frühbeck, G


    Adipose tissue responds dynamically to alterations in nutrient excess through adipocyte hypertrophy and hyperplasia, followed by increased angiogenesis, immune cell infiltration, extracellular matrix (ECM) overproduction, and thus, increased production of proinflammatory adipokines during the progression of chronic inflammation. Adipose tissue remodelling is an ongoing process that is pathologically accelerated in the obese state in large part mediated by ECM proteins and proteases. The ECM is subject to major modifications by adipocytes and other cell types that are infiltrated in the adipose tissue, such as macrophages and vascular cells. In obesity, unusual expression of ECM components and fragments derived from tissue-remodelling processes can influence immune cell recruitment and activation, actively contributing to inflammation. ECM turnover requires a tightly regulated balance between the synthesis of the components and their proteolysis, mainly by fibrinolytic systems and matrix metalloproteases (MMPs). In this review, we discuss the key cellular steps that lead to adipose tissue remodelling and the main molecular mechanisms and mediators in this process. We highlight the importance of hypoxia and angiogenesis in the adipose remodelling process, as well as the cross-talk between adipocytes, macrophages and ECM components.

  20. Demonstration of Osteocytic Perilacunar/Canalicular Remodeling in Mice during Lactation (United States)

    Qing, Hai; Ardeshirpour, Laleh; Pajevic, Paola Divieti; Dusevich, Vladimir; Jähn, Katharina; Kato, Shigeaki; Wysolmerski, John; Bonewald, Lynda F.


    Osteoclasts are thought to be solely responsible for the removal of bone matrix. However, we show here that osteocytes can also remove bone matrix by reversibly remodeling their perilacunar/canalicular matrix during the reproductive cycle. In contrast, no osteocytic remodeling was observed with experimental unloading despite similar degrees of bone loss. Gene array analysis of osteocytes from lactating animals revealed an elevation of genes known to be utilized by osteoclasts to remove bone including Tartrate Resistant Acid Phosphatase, TRAP, and cathepsin K that returned to virgin levels upon weaning. Infusion of Parathyroid Hormone Related Peptide, PTHrP, known to be elevated during lactation, induced TRAP activity and cathepsin K expression in osteocytes concurrent with osteocytic remodeling. Conversely, animals lacking the Parathyroid Hormone Type 1 receptor, PTHR1, in osteocytes failed to express TRAP or cathepsin K or to remodel their osteocyte perilacunar matrix during lactation. These studies show that osteocytes remove mineralized matrix through molecular mechanisms similar to those utilized by osteoclasts. PMID:22308018

  1. Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction. (United States)

    Lassen, Thomas Ravn; Nielsen, Jan Møller; Johnsen, Jacob; Ringgaard, Steffen; Bøtker, Hans Erik; Kristiansen, Steen Buus


    Left ventricular (LV) remodeling following a myocardial infarction (MI) involves formation of reactive oxygen species (ROS). Paroxetine, a selective serotonin reuptake inhibitor, has an antioxidant effect in the vascular wall. We investigated whether paroxetine reduces myocardial ROS formation and LV remodeling following a MI. In a total of 32 Wistar rats, MI was induced by a 30-min ligation of the left anterior descending artery followed by 7- or 28-day reperfusion. During the 28 days of reperfusion, LV remodeling was evaluated by magnetic resonance imaging (MRI) and echocardiography (n = 20). After 28 days of reperfusion, the susceptibility to ventricular tachycardia was evaluated prior to sacrifice and histological assessment of myocyte cross-sectional area, fibrosis, and presence of myofibroblasts. Myocardial ROS formation was measured with dihydroethidium after 7 days of reperfusion in separate groups (n = 12). Diastolic LV volume, evaluated by MRI (417 ± 60 vs. 511 ± 64 µL, p paroxetine group than in controls. Furthermore, myocyte cross-sectional area was reduced in the paroxetine group compared with controls (277 ± 26 vs. 354 ± 23 mm(3), p paroxetine reduced the susceptibility to ventricular tachycardia (induced in 2/11 vs. 6/8 rats, p Paroxetine treatment following MI decreases LV remodeling and susceptibility to arrhythmias, probably by reducing ROS formation.

  2. Osteoblastogenesis and Role of Osteoblasts in Calcıum Homeostasis and Remodeling of Bone

    Directory of Open Access Journals (Sweden)

    Neslihan Başcıl Tütüncü


    Full Text Available Bone remodeling is very important for repair of microfractures and fatigue damage and prevention of excessive aging and its consequences. Bone remodeling lasts for about 6-9 months. During this period osteoclasts resorb damaged bone and osteoblasts synthesize new bone. The lifespan of mature osteoclasts is about 15 days and for osteoblasts 3 months. Therefore, the time required for the remodeling of a given segement of bone is much longer than the lifespan of its cells which perform remodeling. A supply of new osteoblasts and osteoclasts are therefore needed for succesful remodeling by the basic multicellular unit. The major event that triggers osteogenesis is the transition of mesenchymal stem cells into bone differentiating osteoblast cells. Osteoblast commitment and differentation are controlled by complex activities. Many factors are involved in the regulation of osteoblastogenesis. Bone morphogenetic proteins and the Wnt glycoproteins play crucial roles in signaling osteoblast commitment and differentiation, and are the only known factors capable of initiating osteoblastogenesis from uncommitted progenitors. They can initiate commitment of mesenchymal cells to osteoblastic lineage. The initial cell division is asymmetric, giving rise to another stem cell and a committed osteoprogenitor. After commitment to the osteoblastic lineage, a osteoprogenitor cell gives rise to the transit-amplifying compartment. At this stage osteoprogenitor cells proliferate intensively. After this stage, the cells are more differentiated and give rise to preosteoblasts which express both STRO1, alkaline phosphatase, pyrophosphate, and type 1 collagen. Preosteoblasts are committed to the osteoblast lineage with extensive replicative capacity, but have no self-renewal capacity. Preosteoblasts form the intermediate stage of osteoblastogenesis. The mature osteoblasts express osteopontin, alkaline phosphatase, bone sialoprotein, and osteocalcin. This stage is

  3. Inflammation is Associated with Vascular Remodeling - Repairing Balances in Hypertensive Obese Subjects

    Directory of Open Access Journals (Sweden)

    Lies Gantini


    Full Text Available BACKGROUND: Hypertension and obesity are proinflammatory conditions. Vascular remodeling is one of the pathomechanisms reflecting increased cardiovascular (CV risks and represented as ratio of MMP-9 and sVEGFR-2 concentration. There is no association confirmed between inflammation and remodeling yet. This study was conducted to investigate the correlation between inflammation and vascular remodeling-repairing balances in hypertensive obese subjects. METHODS: This was a cross–sectional study recruited 34 hypertensive obese subjects and 10 hypertensive non obese subjects. They had no antihypertensive medications, neither diabetics nor renal disease and nor acute inflammation detected. Inflammation was assessed as increased hsCRP concentration. Vascular remodeling and repairing were consecutively represented by ratio of MMP-9 and sVEGFR-2. RESULTS: Concentration of hsCRP and MMP-9 were significantly higher in hypertensive obese group than non obese group (2.094±1.90 vs. 0.714±0.40 mg/L; p=0.029; 363.43±143.64 vs. 261.15±61.13 ng/mL, p=0.035, respectively, nonetheless no significant differences of sVEGFR-2 concentration (9.77±2.30 vs. 9.76±1.38 pg/mL, p=0.980 found in both groups. Ratio of MMP-9/sVEGFR-2 was significantly higher in hypertensive obese group than those in non-obese group (38.67±16 vs. 27.22±10, p=0.038. Likewise, they had more subjects with ratio of MMP-9/sVEGFR-2 ≥31.53. This figure is considered as cut-off point of vascular remodeling versus repairing. CONCLUSIONS: In hypertensive obese subjects, inflammation was activated and vascular remodeling more dominant than repairing process. Inflammation was associated with increased remodeling-repairing balances. KEYWORDS: matrix metalloproteinase-9 (MMP-9, soluble vascular endothelial growth factor receptor-2 (sVEGFR-2, high sensitivity C-Reactive Protein (hsCRP.

  4. Exercise-induced inhibition of remodelling is focally offset with fatigue fracture in racehorses. (United States)

    Whitton, R C; Mirams, M; Mackie, E J; Anderson, G A; Seeman, E


    Bone remodelling is inhibited by high repetitive loading. However, in subchondral bone of racehorses in training, eroded surface doubled in association with fatigue fracture and there was greater surrounding trabecular bone volume suggesting trabecular modelling unloads the bone focally, allowing damage repair by remodelling. Remodelling replaces damaged bone with new bone but is suppressed during high magnitude repetitive loading when damage is most likely. However, in cortical bone of racehorses, at sites of fatigue fracture, focal porosity, consistent with remodelling, is observed in proportion to the extent of surrounding callus. Focal areas of porosity are also observed at sites of fatigue damage in subchondral bone. We hypothesised that fatigued subchondral bone, like damaged cortical bone, is remodelled focally in proportion to the modelling of surrounding trabecular bone. Eroded and mineralizing surfaces and bone area were measured using backscattered scanning electron microscopy of post-mortem specimens of the distal third metacarpal bone in 11 racehorses with condylar fractures (cases) and eight racehorses in training without fractures (controls). Cases had a two-fold greater eroded surface per unit area at the fracture site than controls (0.81 ± 0.10 vs. 0.40 ± 0.12 mm(-1), P = 0.021) but not at an adjacent site (0.22 ± 0.09 vs. 0.30 ± 0.11 mm(-1), P = 0.59). Area fraction of surrounding trabecular bone was higher in cases than controls (81 ± 2 vs. 72 ± 2 %, P = 0.0020) and the eroded surface at the fracture site correlated with the surrounding trabecular area (adjusted R (2) = 0.63, P = 0.0010). In conclusion, exercise-induced inhibition of remodelling is offset at sites of fatigue fracture. Modelling of trabecular bone may contribute to unloading these regions, allowing repair by remodelling.

  5. Quantification of collagen and proteoglycan deposition in a murine model of airway remodelling (United States)

    Reinhardt, Alistair K; Bottoms, Stephen E; Laurent, Geoffrey J; McAnulty, Robin J


    Background Sub-epithelial extracellular matrix deposition is a feature of asthmatic airway remodelling associated with severity of disease, decline in lung function and airway hyperresponsiveness. The composition of, and mechanisms leading to, this increase in subepithelial matrix, and its importance in the pathogenesis of asthma are unclear. This is partly due to limitations of the current models and techniques to assess airway remodelling. Methods In this study we used a modified murine model of ovalbumin sensitisation and challenge to reproduce features of airway remodelling, including a sustained increase in sub-epithelial matrix deposition. In addition, we have established techniques to accurately and specifically measure changes in sub-epithelial matrix deposition, using histochemical and immunohistochemical staining in conjunction with digital image analysis, and applied these to the measurement of collagen and proteoglycans. Results 24 hours after final ovalbumin challenge, changes similar to those associated with acute asthma were observed, including inflammatory cell infiltration, epithelial cell shedding and goblet cell hyperplasia. Effects were restricted to the bronchial and peribronchial regions with parenchymal lung of ovalbumin sensitised and challenged mice appearing histologically normal. By 12 days, the acute inflammatory changes had largely resolved and increased sub-epithelial staining for collagen and proteoglycans was observed. Quantitative digital image analysis confirmed the increased deposition of sub-epithelial collagen (33%, p proteoglycans (32%, p proteoglycan deposition in an animal model of airway remodelling. This model will be useful for measurement of other matrix components, as well as for assessment of the molecular mechanisms contributing to, and agents to modulate airway remodelling. PMID:15819978

  6. Remodeling of the myocardium in early trabeculation and cardiac valve formation; a role for TGFβ2. (United States)

    Kruithof, Boudewijn P T; Kruithof-De-Julio, Marianna; Poelmann, Robert E; Gittenberger-De-Groot, Adriana C; Gaussin, Vinciane; Goumans, Marie-José


    Trabeculation and the formation of the leaflets of the mitral and tricuspid valves both involve remodeling of the embryonic myocardium. The nature and possible connection of these myocardial remodeling processes, however, are unclear. Therefore, we examined the morphogenesis of the early ventricular and atrioventricular (AV) myocardium and report for the first time that the formation of the early trabeculae and the positioning of the valve primordia (endocardial cushions) into the ventricular lumen are part of one continuous myocardial remodeling process, which involves the dissociation of the myocardial layers. For the endocardial cushions, this process results in delamination from the AV myocardium. The AV myocardium that will harbor the right lateral cushion is the exception and becomes positioned in the ventricular lumen by folding of the right ventricle. As a consequence, remodeling of the left and right AV myocardium occurs differently with implications for the formation of the mural leaflets and annulus fibrosis. At both the right and left side, the valvular myocardium harbors a distinct molecular phenotype and its removal from the cardiac leaflets involves a second wave of delamination. Interestingly, in the TGFβ2-KO mouse, which is a known model for cushion and valve defects, remodeling of the early myocardium is disturbed as indicated by defective trabeculae formation, persistence of valvular myocardium, disturbed myocardial phenotypes and differential defects at left and right side of the AV canal. Based on these results we propose a new model clarifying early trabeculae formation and AV valve formation and provide new inroads for an enhanced understanding of congenital heart defects.

  7. Adverse impact of diabetes mellitus on left ventricular remodelling in patients with chronic primary mitral regurgitation. (United States)

    Ernande, Laura; Beaudoin, Jonathan; Piro, Victoria; Meziani, Souhila; Scherrer-Crosbie, Marielle


    Diabetes mellitus (DM) has an impact on left ventricular (LV) geometry and function, and is associated with worsening of pressure-overload LV remodelling; however, its impact on volume-overload LV remodelling is unknown. The objective of the study was to examine the association between DM and LV remodelling in patients with chronic mitral regurgitation (MR) caused by mitral valve prolapse. During a median follow-up of 3.26 [interquartile range 1.59-6.06] years, we evaluated the evolution of echocardiographic variables in 375 consecutive patients, including 61 (16%) patients with DM. The main endpoint was LV remodelling evaluated by LV end-diastolic diameter (LVEDD) and LV mass index increase. LV end-systolic diameter (LVESD) and ejection fraction (LVEF) were also evaluated. Patients with DM increased their LVEDD more than patients without DM (1.98±4.1 vs 0.15±4.54mm/year of follow-up; P=0.002). LVEF remained stable in the two groups. After adjustment for potential confounders, including age, sex, hypertension, body mass index, MR severity, medications and follow-up duration, DM remained independently associated with LVEDD increase (β=2.30; P<0.001). When comparing patients with DM with patients without DM matched for age, sex and LVEDD at baseline, DM was independently associated with increased LVEDD (β=2.14; P=0.002), LV mass index (β=10.7; P=0.004) and LVESD (β=2.07; P=0.01). DM is associated with worsening of LV remodelling in patients with moderate or severe chronic MR caused by mitral valve prolapse. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  8. Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.

    Directory of Open Access Journals (Sweden)

    Juan F Gomez

    Full Text Available Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure.In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations.The electrical activity of human transmural ventricular tissue (5 cm × 5 cm was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW for reentry was evaluated following cross-field stimulation.No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components.Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity.

  9. nNOS is involved in cardiac remodeling induced by chronic ethanol consumption. (United States)

    Silva, Susana M; Silva, Sérgio; Meireles, Manuela; Leal, Sandra


    Chronic ethanol consumption has deleterious effects on the cardiovascular system by directly damaging the myocardial structure and/or by neurohormonal activation. Moreover, nitric oxide (NO) derived from neuronal NO synthase (nNOS) seems to be important to balance the harmful effects of ethanol consumption, because it influences several aspects of cardiac physiology and attenuates pathological cardiac remodeling. However, the impact of chronic ethanol consumption on nNOS expression is unknown. We address this subject in the present study by evaluating whether chronic ethanol consumption induces cardiac remodeling and hypertension, and if these changes are associated with alterations in the expression of nNOS. Male Wistar rats were examined after ingesting a 20% alcohol solution for 6 months. Blood alcohol concentration and brain natriuretic peptide (BNP) levels were measured. The cardiac remodeling was assessed by histomorphometric analysis and the nNOS expression was evaluated by immunofluorescence and western blot analysis. Our results show that chronic ethanol consumption induces cardiac remodeling, namely thinning of left ventricular wall, cardiomyocyte hypertrophy and increased fibrosis, and elevations of arterial blood pressure. They also show that in rats fed with ethanol for 6 months, the circulating BNP levels had decreased as well as the expression of nNOS in left ventricle cardiomyocytes. These findings suggest that the effects of chronic ethanol consumption on BNP levels and/or on nNOS expression in cardiomyocytes may contribute to aggravate the cardiac remodeling and leads to progression of cardiomyopathy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Morphological remodeling of C. elegans neurons during aging is modified by compromised protein homeostasis. (United States)

    Vayndorf, Elena M; Scerbak, Courtney; Hunter, Skyler; Neuswanger, Jason R; Toth, Marton; Parker, J Alex; Neri, Christian; Driscoll, Monica; Taylor, Barbara E

    Understanding cellular outcomes, such as neuronal remodeling, that are common to both healthy and diseased aging brains is essential to the development of successful brain aging strategies. Here, we used Caenorhabdits elegans to investigate how the expression of proteotoxic triggers, such as polyglutamine (polyQ)-expanded huntingtin and silencing of proteostasis regulators, such as the ubiquitin-proteasome system (UPS) and protein clearance components, may impact the morphological remodeling of individual neurons as animals age. We examined the effects of disrupted proteostasis on the integrity of neuronal cytoarchitecture by imaging a transgenic C. elegans strain in which touch receptor neurons express the first 57 amino acids of the human huntingtin (Htt) gene with expanded polyQs (128Q) and by using neuron-targeted RNA interference in adult wild-type neurons to knockdown genes encoding proteins involved in proteostasis. We found that proteostatic challenges conferred by polyQ-expanded Htt and knockdown of specific genes involved in protein homeostasis can lead to morphological changes that are restricted to specific domains of specific neurons. The age-associated branching of PLM neurons is suppressed by N-ter polyQ-expanded Htt expression, whereas ALM neurons with polyQ-expanded Htt accumulate extended outgrowths and other soma abnormalities. Furthermore, knockdown of genes important for ubiquitin-mediated degradation, lysosomal function, and autophagy modulated these age-related morphological changes in otherwise normal neurons. Our results show that the expression of misfolded proteins in neurodegenerative disease such as Huntington's disease modifies the morphological remodeling that is normally associated with neuronal aging. Our results also show that morphological remodeling of healthy neurons during aging can be regulated by the UPS and other proteostasis pathways. Collectively, our data highlight a model in which morphological remodeling during neuronal

  11. Early repair of moderate ischemic mitral regurgitation reverses left ventricular remodeling: a functional and molecular study. (United States)

    Beeri, Ronen; Yosefy, Chaim; Guerrero, J Luis; Abedat, Suzan; Handschumacher, Mark D; Stroud, Robert E; Sullivan, Suzanne; Chaput, Miguel; Gilon, Dan; Vlahakes, Gus J; Spinale, Francis G; Hajjar, Roger J; Levine, Robert A


    Mitral regurgitation (MR) doubles postmyocardial infarction (MI) mortality. We have shown that moderate MR augments remodeling in an apical MI model (no intrinsic MR) with independent left ventricle-to-left atrial MR-type flow. We hypothesized that repairing moderate MR 1 month after MI reverses this remodeling. Anteroapical MIs were created in 18 sheep, and a left ventricle-to-left atrial shunt implanted in 12 (regurgitant fraction, 30%). Six sheep had the shunt closed at 1 month (repair group). Sheep were compared at baseline, and at 1 and 3 months. Sheep in the MI+MR (unrepaired) and repaired groups remodeled during the first month (120% increased left ventricular end-systolic volume [ESV; P<0.01]), but shunt closure reversed remodeling at 3 months, with end-diastolic volume (EDV) and ESV 135% and 128% of baseline versus 220% and 280% without repair (P<0.001). At 3 months, dP/dt and preload-recruitable stroke work were relatively maintained in the repaired and MI-only groups versus nearly 50% decreases without repair. Prohypertrophic gp130 and antiapoptotic pAkt increased followed by exhaustion below baseline without repair, but remained elevated at 3 months with repair or MI only. With repair, matrix metalloproteinase-2 decreased to < or = 50% that without repair in remote and border zones at 3 months, and the matrix metalloproteinase inhibitor TIMP-4 increased dramatically. Early repair of moderate MR in the setting of apical MI substantially reverses the otherwise progressive remodeling process, with reduced left ventricular volumes, relatively maintained contractility, persistently activated intracellular signals promoting hypertrophy and opposing apoptosis, and reduced matrix proteolytic activity. These findings are of interest for the current controversy regarding potential benefits of repair of MR after MI.

  12. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction. (United States)

    Wang, Wei; Zhang, Fuyang; Xia, Yunlong; Zhao, Shihao; Yan, Wenjun; Wang, Helin; Lee, Yan; Li, Congye; Zhang, Ling; Lian, Kun; Gao, Erhe; Cheng, Hexiang; Tao, Ling


    Cardiac metabolic remodeling is a central event during heart failure (HF) development following myocardial infarction (MI). It is well known that myocardial glucose and fatty acid dysmetabolism contribute to post-MI cardiac dysfunction and remodeling. However, the role of amino acid metabolism in post-MI HF remains elusive. Branched chain amino acids (BCAAs) are an important group of essential amino acids and function as crucial nutrient signaling in mammalian animals. The present study aimed to determine the role of cardiac BCAA metabolism in post-MI HF progression. Utilizing coronary artery ligation-induced murine MI models, we found that myocardial BCAA catabolism was significantly impaired in response to permanent MI, therefore leading to an obvious elevation of myocardial BCAA abundance. In MI-operated mice, oral BCAA administration further increased cardiac BCAA levels, activated the mammalian target of rapamycin (mTOR) signaling, and exacerbated cardiac dysfunction and remodeling. These data demonstrate that BCAAs act as a direct contributor to post-MI cardiac pathologies. Furthermore, these BCAA-mediated deleterious effects were improved by rapamycin cotreatment, revealing an indispensable role of mTOR in BCAA-mediated adverse effects on cardiac function/structure post-MI. Of note, pharmacological inhibition of branched chain ketoacid dehydrogenase kinase (BDK), a negative regulator of myocardial BCAA catabolism, significantly improved cardiac BCAA catabolic disorders, reduced myocardial BCAA levels, and ameliorated post-MI cardiac dysfunction and remodeling. In conclusion, our data provide the evidence that impaired cardiac BCAA catabolism directly contributes to post-MI cardiac dysfunction and remodeling. Moreover, improving cardiac BCAA catabolic defects may be a promising therapeutic strategy against post-MI HF. Copyright © 2016 the American Physiological Society.

  13. Three dimensional assessment of condylar surface changes and remodeling after orthognathic surgery

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Hye; Lee, Jin Woo; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Dental Research Institute, Seoul National University, Seoul (Korea, Republic of); Shin, Jae Myung [Dept. of Oral and Maxillofacial Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang (Korea, Republic of)


    This study was performed to evaluate condylar surface changes and remodeling after orthognathic surgery using three-dimensional computed tomography (3D CT) imaging, including comparisons between the right and left sides and between the sexes. Forty patients (20 males and 20 females) who underwent multi-detector CT examinations before and after surgery were selected. Three-dimensional images comprising thousands of points on the condylar surface were obtained before and after surgery. For the quantitative assessment of condylar surface changes, point-to-point (preoperative-to-postoperative) distances were calculated using D processing software. These point-to-point distances were converted to a color map. In order to evaluate the types of condylar remodeling, the condylar head was divided into six areas (anteromedial, anteromiddle, anterolateral, posteromedial, posteromiddle, and posterolateral areas) and each area was classified into three types of condylar remodeling (bone formation, no change, and bone resorption) based on the color map. Additionally, comparative analyses were performed between the right and left sides and according to sex. The mean of the average point-to-point distances on condylar surface was 0.11±0.03 mm. Bone resorption occurred more frequently than other types of condylar remodeling, especially in the lateral areas. However, bone formation in the anteromedial area was particularly prominent. No significant difference was found between the right and left condyles, but condylar surface changes in males were significantly larger than in females. This study revealed that condylar remodeling exhibited a tendency towards bone resorption, especially in the lateral areas. Condylar surface changes occurred, but were small.

  14. Fiber architecture in remodeled myocardium revealed with a quantitative diffusion CMR tractography framework and histological validation

    Directory of Open Access Journals (Sweden)

    Mekkaoui Choukri


    Full Text Available Abstract Background The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Methods Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. Results In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 ± 0.16 in normal hearts to 0.22 ± 0.08 in the remote zone of the remodeled hearts (p Conclusions A significant reorganization of the 3D fiber continuum is observed in the remote zone of remodeled hearts. The positive (rightward shift in HA in the remote zone is greatest in the subepicardium, but involves all layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

  15. A continuum mechanics framework and a constitutive model for remodelling of collagen gels and collagenous tissues (United States)

    Kroon, Martin


    Collagen is a very important protein of the human body and is responsible for the structural stability of many body components. Furthermore, collagen fibre networks are able to grow and remodel themselves, which enables them to adjust to varying physiological conditions. This remodelling is accomplished by fibre-producing cells, such as fibroblasts. The ability to adjust to new physiological conditions is very important, for example in wound healing. In the present paper, a theoretical framework for modelling collagenous tissues and collagen gels is proposed. Continuum mechanics is employed to describe the kinematics of the collagen, and affine deformations of fibres are assumed. Biological soft tissues can be approximated as being hyperelastic, and the constitutive model for the collagen fabric is therefore formulated in terms of a strain energy function. This strain energy function includes a density function that describes the distribution of the collagen fibre orientation. The density function evolves according to an evolution law, where fibres tend to reorient towards the direction of maximum Cauchy stress. The remodelling of the collagen network is also assumed to include a pre-stretching of collagen fibres, accomplished by fibroblasts. The theoretical framework is applied to experiments performed on collagen gels, where gels were exposed to remodelling under both biaxial and uniaxial constraints. The proposed model was able to predict both the resulting collagen distribution and the resulting stress-strain relationships obtained for the remodelled collagen gels. The influence of the most important model parameters is demonstrated, and it appears that there is a fairly unique set of model parameters that gives an optimal fit to the experimental data.

  16. Remodeling Tulang Alveolar untuk Reimplantasi dan Transplantasi Gigi Anterior pada Kehilangan Tulang Hebat Paska Trauma

    Directory of Open Access Journals (Sweden)

    Heru Maksmara


    Full Text Available Latar Belakang. Remodeling tulang alveolar berguna untuk memperbaiki kehilangan struktur jaringan pendukung gigi yang hebat pada reimplantasi dan transplantasi gigi anterior, supaya gigi anterior yang terlepas dari soketnya paska trauma dapat di implantasi. Bahan cangkok tulang untuk remodeling tulang alveolar yang digunakan berjenis demineralized freeze-dried bone allograft (DFDBA. Tujuan Penulisan Laporan Kasus. Melaporkan keberhasilan menanam gigi tetap ditempatnya dengan teknik remodeling tulang dengan penambahan DFDBA agar struktur jaringan pendukung gigi yang hilang kembali normal. Penatalaksanaan. Pasien paska trauma, dalam keadaan tidak sadar selama 7 hari di ruang rawat intensif dan dirawat selama 7 hari di bangsal. Pasien mengalami trauma dan kehilangan tulang penyangga gigi yang hebat, pada gigi anterior bawah. Tiga gigi anterior mengalami kegoyahan 4° dan dua gigi hilang. Hilangnya dua gigi mengakibatkan area edentulous besar, sehingga perlu di lakukan transplantasi satu gigi. Untuk memperkecil edentulous dilakukan penambahan lebar mahkota gigi menggunakan composite light curing. Setelah pencabutan gigi, semua gigi yang akan di implant dilakukan perawatan saluran akar gigi dan disterilkan. Flap operasi dilakukan untuk menata serpihan tulang dan menilai besarnya trauma, daerah luka dibersihkan dengan lIarutan salin. Splinting semua gigi yang akan di implant menggunakan arch bar dan kawat. Penambahan bahan cangkok tulang DFDBA pada daerah operasi. Menjahit daerah operasi ke korona gigi dan ditutup pack. Setelah 6 bulan operasi dua gigi tidak men gal ami kegoyahan, dua gigi lain mengalami kegoyahan 2°, 12 bulan tiga gigi tidak mengalami kegoyahan dan hanya satu gigi transplantasi yang mengalami kegoyahan 1°. Re-entry operasi dilakukan untuk remodeling tulang bertambah baik. Setelah 6 bulan paska re-entry operasi, gigi yang di transplantasi tidak mengalami kegoyahan. Sehingga splint dapat dilepas. Kesimpulan. Remodeling tulang pada

  17. Pulmonary hypertension and vascular remodeling in mice exposed to crystalline silica. (United States)

    Zelko, Igor N; Zhu, Jianxin; Ritzenthaler, Jeffrey D; Roman, Jesse


    Occupational and environmental exposure to crystalline silica may lead to the development of silicosis, which is characterized by inflammation and progressive fibrosis. A substantial number of patients diagnosed with silicosis develop pulmonary hypertension. Pulmonary hypertension associated with silicosis and with related restrictive lung diseases significantly reduces survival in affected subjects. An animal model of silicosis has been described previously however, the magnitude of vascular remodeling and hemodynamic effects of inhaled silica are largely unknown. Considering the importance of such information, this study investigated whether mice exposed to silica develop pulmonary hypertension and vascular remodeling. C57BL6 mice were intratracheally injected with either saline or crystalline silica at doses 0.2 g/kg, 0.3 g/kg and 0.4 g/kg and then studied at day 28 post-exposure. Pulmonary hypertension was characterized by changes in right ventricular systolic pressure and lung histopathology. Mice exposed to saline showed normal lung histology and hemodynamic parameters while mice exposed to silica showed increased right ventricular systolic pressure and marked lung pathology characterized by a granulomatous inflammatory reaction and increased collagen deposition. Silica-exposed mice also showed signs of vascular remodeling with pulmonary artery muscularization, vascular occlusion, and medial thickening. The expression of pro-inflammatory genes such as TNF-α and MCP-1 was significantly upregulated as well as the expression of the pro-remodeling genes collagen type I, fibronectin and the metalloproteinases MMP-2 and TIMP-1. On the other hand, the expression of several vasculature specific genes involved in the regulation of endothelial function was significantly attenuated. We characterized a new animal model of pulmonary hypertension secondary to pulmonary fibrosis induced by crystalline silica. Our data suggest that silica promotes the damage of the

  18. High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD – results from the ECLIPSE study

    DEFF Research Database (Denmark)

    Sand, Jannie M B; Leeming, Diana J; Byrjalsen, Inger


    BACKGROUND: There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with morta......BACKGROUND: There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated...... with mortality in COPD and measured neo-epitopes originating from ECM proteins associated with lung tissue remodeling. METHODS: Biomarkers of ECM remodeling were assessed in a subpopulation (n = 1000) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort. Validated......: Serological biomarkers of collagen remodeling were strongly associated with mortality in subjects with COPD indicating that assessment of tissue turnover in the parenchyma and small airways may be useful in the prognosis of COPD. TRIAL REGISTRATION: NCT00292552 , GSK Study No. SCO104960....

  19. Bone remodelling in vitro: Where are we headed?: -A review on the current understanding of physiological bone remodelling and inflammation and the strategies for testing biomaterials in vitro. (United States)

    Kohli, Nupur; Ho, Sonia; Brown, Stuart J; Sawadkar, Prasad; Sharma, Vaibhav; Snow, Martyn; García-Gareta, Elena


    Bone remodelling is a dynamic process required for the maintenance of bone architecture in response to the changing mechanical needs. It is also a vital process during the repair of bone tissue following injury. Clinical intervention in terms of autografting or allografting is often required to heal bone injuries where physiological healing fails. The use of biomaterials as alternatives to autografts and allografts has spurred a significant research interest into further development of biomaterials for better clinical outcomes. Unfortunately, many biomaterials fail to make it to the clinic or fail after implantation due to the inconsistencies observed between in vitro and in vivo studies. It is therefore important to mimic the in vivo situation as closely as possible in an in vitro setting for testing biomaterials. The current in vitro models focus mostly on investigating the behaviour of osteoblast progenitors with the biomaterial under development as well as assessing the behaviour of osteoclasts, endothelial cells etc. However, the sequence of events that take place during bone healing or remodelling are not incorporated into the current in vitro models. This review highlights our current understanding of the physiological bone remodelling and the bone healing process followed by strategies to incorporate both the physiological and pathophysiological events into an in vitro environment. Here, we propose three strategies for the assessment of biomaterials for bone, which includes; (1) testing biomaterials in the presence of immune cells, (2) testing biomaterials for osteogenesis, and (3) testing biomaterials in the presence of osteoclasts followed by osteoblasts to recapitulate the physiological events of bone resorption prior to bone formation. The focus of this review is to discuss the third strategy in details as the first two strategies are currently incorporated into a majority of in vitro experiments. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Strategies for Energy-Efficient Remodeling: SEER 2003 Case Study Report; February 27, 2003 -- October 31, 2004

    Energy Technology Data Exchange (ETDEWEB)

    Drumheller, S. C.; Wiehagen, J.


    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance. Opportunities to include energy efficiency often arise while undertaking general remodeling work. This case study report examines the technologies, methods, and installation of specific energy efficiency strategies. The information presented here stems from a ''gut rehab'' of a house in rural New Jersey as part of the SEER project through the Building America Existing Buildings Program.

  1. Left ventricular remodeling and fibrosis: Sex differences and relationship with diastolic function in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, You-Zhou [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Qiao, Shu-Bin, E-mail: [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Hu, Feng-Huan; Yuan, Jian-Song; Yang, Wei-Xian; Cui, Jin-Gang [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Yan [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Chang-Lin [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)


    Highlights: • There are significant differences in LV remodeling and fibrosis as divided by sex. • Women have worse diastolic dysfunction compared to men measured by CMR. • LV remodeling and fibrosis correlate with markers of diastolic dysfunction. - Abstract: Objectives: We investigated sex differences in left ventricular (LV) remodeling and fibrosis and their relationship with LV diastolic dysfunction by cardiovascular magnetic resonance (CMR). Methods: CMR imaging was performed simultaneously in 152 age-matched patients (76 men, 76 women; mean age: 49 ± 9 years) without LV systolic dysfunction. LV remodeling index (LVRI) was calculated as the ratio of LV mass and end-diastolic volume. Diastolic function indexes including peak filling rate (PFR) and time to PFR (tPFR) were evaluated. Extent of late gadolinium enhancement (LGE) was measured. Results: LVRI and extent of LGE were greater in women compared with men (1.48 ± 0.22 vs. 1.36 ± 0.28 g/ml; 13.15 ± 2.48 vs. 11.35 ± 2.34 g, respectively, both P < 0.001). Women had lower PFR and higher tPFR (both P < 0.001) than men. LVRI and the extent of LGE showed significant relationships with parameters of diastolic function in both sex. In a multivariate analysis, LVRI remained a strong independent predictor of PFR and TPFR in women (β = −0.272, P = 0.032; β = 0.348, P = 0.016, respectively), and in men (β = −0.374, P < 0.001; β = 0.660, P < 0.001, respectively). Furthermore, the extent of LGE also remained an independent predictor of PFR in women (β = −0.283, P = 0.033) and men (β = −0.492, P < 0.001). Conclusions: There are prominent sex differences in LV remodeling and myocardial fibrosis. We suggest that the effects of LV remodeling and fibrosis may lead to diastolic dysfunction with greater susceptibility to worse clinical outcome in women.

  2. NMDA-Type Glutamate Receptor Activation Promotes Vascular Remodeling and Pulmonary Arterial Hypertension. (United States)

    Dumas, Sébastien J; Bru-Mercier, Gilles; Courboulin, Audrey; Quatredeniers, Marceau; Rücker-Martin, Catherine; Antigny, Fabrice; Nakhleh, Morad K; Ranchoux, Benoit; Gouadon, Elodie; Vinhas, Maria-Candida; Vocelle, Matthieu; Raymond, Nicolas; Dorfmüller, Peter; Fadel, Elie; Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia


    Background -Excessive proliferation and apoptosis resistance in pulmonary vascular cells underlie vascular remodeling in pulmonary arterial hypertension (PAH). Specific treatments for PAH exist, mostly targeting endothelial dysfunction, but high pulmonary arterial pressure still causes heart failure and death. Pulmonary vascular remodeling may be driven by metabolic reprogramming of vascular cells to increase glutaminolysis and glutamate production. The N-methyl-D-aspartate receptor (NMDAR), a major neuronal glutamate receptor, is also expressed on vascular cells, but its role in PAH is unknown. Methods -We assessed the status of the glutamate-NMDAR axis in the pulmonary arteries of PAH patients and controls, through mass spectrometry imaging, western blotting and immunohistochemistry. We measured the glutamate release from cultured pulmonary vascular cells using enzymatic assays, and analyzed NMDAR regulation/phosphorylation through western blot experiments. The effect of NMDAR blockade on human pulmonary arterial smooth muscle cell (hPASMC) proliferation was determined using a BrdU incorporation assay. We assessed the role of NMDARs in vascular remodeling associated to pulmonary hypertension (PH), both in smooth muscle-specific NMDAR knockout mice exposed to chronic hypoxia and in the monocrotaline rat model of PH using NMDAR blockers. Results -We report glutamate accumulation, upregulation of the NMDAR, and NMDAR engagement reflected by increases in GluN1-subunit phosphorylation, in the pulmonary arteries of human PAH patients. K v channel inhibition and ETAR activation amplified calcium-dependent glutamate release from hPASMCs, and ETAR and PDGFR activation led to NMDAR engagement, highlighting crosstalk between the glutamate-NMDAR axis and major PAH-associated pathways. The PDGF-BB-induced proliferation of hPASMCs involved NMDAR activation and phosphorylated GluN1 subunit localization to cell-cell contacts, consistent with glutamatergic communication between

  3. [Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure: Part I]. (United States)

    Sirico, Domenico; Salzano, Andrea; Celentani, Dario; Arcopinto, Michele; Marra, Alberto Maria; Bobbio, Emanuele; Russo, Angelo; Giallauria, Francesco; Vigorito, Carlo


    In recent years, the remarkable progress achieved in terms of survival after myocardial infarction have led to an increased incidence of chronic heart failure in survivors. This phenomenon is due to the still incomplete knowledge we possess about the complex pathophysiological mechanisms that regulate the response of cardiac tissue to ischemic injury. These involve various cell types such as fibroblasts, cells of the immune system, endothelial cells, cardiomyocytes and stem cells, as well as a myriad of mediators belonging to the system of cytokines and not only. In parallel with the latest findings on post-infarct remodeling, new potential therapeutic targets are arising to halt the progression of disease. In this review, we evaluate the results obtained from four new therapeutic strategies: in this part we evaluate gene therapy and novel aspect of stem cells therapy in remodeling; in the second part we will investigate, micro-RNA, posttranslational modification and microspheres based therapy.

  4. Localized Chemical Remodeling for Live Cell Imaging of Protein-Specific Glycoform. (United States)

    Hui, Jingjing; Bao, Lei; Li, Siqiao; Zhang, Yi; Feng, Yimei; Ding, Lin; Ju, Huangxian


    Live cell imaging of protein-specific glycoforms is important for the elucidation of glycosylation mechanisms and identification of disease states. The currently used metabolic oligosaccharide engineering (MOE) technology permits routinely global chemical remodeling (GCM) for carbohydrate site of interest, but can exert unnecessary whole-cell scale perturbation and generate unpredictable metabolic efficiency issue. A localized chemical remodeling (LCM) strategy for efficient and reliable access to protein-specific glycoform information is reported. The proof-of-concept protocol developed for MUC1-specific terminal galactose/N-acetylgalactosamine (Gal/GalNAc) combines affinity binding, off-on switchable catalytic activity, and proximity catalysis to create a reactive handle for bioorthogonal labeling and imaging. Noteworthy assay features associated with LCM as compared with MOE include minimum target cell perturbation, short reaction timeframe, effectiveness as a molecular ruler, and quantitative analysis capability. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration

    DEFF Research Database (Denmark)

    Yui, Shiro; Azzolin, Luca; Maimets, Martti


    sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state. This is characterized by de novo expression of fetal markers as well as suppression of markers for adult stem and differentiated cells. The fate change is orchestrated......Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran...... by remodeling the extracellular matrix (ECM), increased FAK/Src signaling, and ultimately YAP/TAZ activation. In a defined cell culture system recapitulating the extracellular matrix remodeling observed in vivo, we show that a collagen 3D matrix supplemented with Wnt ligands is sufficient to sustain endogenous...

  6. Kinetics of gene expression and bone remodelling in the clinical phase of collagen induced arthritis

    DEFF Research Database (Denmark)

    Denninger, Katja Caroline Marie; Litman, Thomas; Marstrand, Troels


    -wide association studies (GWAS) revealed differential expression of several genes associated with human arthritis. Conclusions: In the CIA model, bone formation in the joint starts shortly after onset of clinical symptoms, which results in bony fusion within one to two weeks. This makes it a candidate model...... of clinical manifestations. The objective of this study was to use this model to characterise the histological and molecular changes in bone remodelling, and relate these to the clinical disease development. Methods: A histological and gene expression profiling time-course study on bone remodelling in CIA...... was linked to onset of clinical symptoms. Global gene expression was studied with a gene chip array system. Results: The main histopathological changes in bone structure and inflammation occurred during the first two weeks following the onset of clinical symptoms in the joint. Hereafter, the inflammation...

  7. Does collagen trigger the recruitment of osteoblasts into vacated bone resorption lacunae during bone remodeling?

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Søe, Kent; Andersen, Thomas Levin


    Osteoblast recruitment during bone remodeling is obligatory to re-construct the bone resorbed by the osteoclast. This recruitment is believed to be triggered by osteoclast products and is therefore likely to start early during the remodeling cycle. Several osteoclast products with osteoblast...... recruitment potential are already known. Here we draw the attention on the osteoblast recruitment potential of the collagen that is freshly demineralized by the osteoclast. Our evidence is based on observations on adult human cancellous bone, combined with in vitro assays. First, freshly eroded surfaces where...... osteoblasts have to be recruited show the presence of non-degraded demineralized collagen and close cell-collagen interactions, as revealed by electron microscopy, while surface-bound collagen strongly attracts osteoblast lineage cells in a transmembrane migration assay. Compared with other extracellular...

  8. Integration of signaling and cytoskeletal remodeling by Nck in directional cell migration. (United States)

    Chaki, Sankar P; Rivera, Gonzalo M


    Planar and apical-basal cellular polarization of epithelia and endothelia are crucial during morphogenesis. The establishment of these distinct polarity states and their transitions are regulated by signaling networks that include polarity complexes, Rho GTPases, and phosphoinositides. The spatiotemporal coordination of signaling by these molecules modulates cytoskeletal remodeling and vesicle trafficking to specify membrane domains, a prerequisite for the organization of tissues and organs. Here we present an overview of how activation of the WASp/Arp2/3 pathway of actin remodeling by Nck coordinates directional cell migration and speculate on its role as a signaling integrator in the coordination of cellular processes involved in endothelial cell polarity and vascular lumen formation.

  9. Remodeling of the cycling transcriptome of the oyster Crassostrea gigas by the harmful algae Alexandrium minutum. (United States)

    Payton, Laura; Perrigault, Mickael; Hoede, Claire; Massabuau, Jean-Charles; Sow, Mohamedou; Huvet, Arnaud; Boullot, Floriane; Fabioux, Caroline; Hegaret, Hélène; Tran, Damien


    As a marine organism, the oyster Crassostrea gigas inhabits a complex biotope governed by interactions between the moon and the sun cycles. We used next-generation sequencing to investigate temporal regulation of oysters under light/dark entrainment and the impact of harmful algal exposure. We found that ≈6% of the gills' transcriptome exhibits circadian expression, characterized by a nocturnal and bimodal pattern. Surprisingly, a higher number of ultradian transcripts were also detected under solely circadian entrainment. The results showed that a bloom of Alexandrium minutum generated a remodeling of the bivalve's temporal structure, characterized by a loss of oscillations, a genesis of de novo oscillating transcripts, and a switch in the period of oscillations. These findings provide unprecedented insights into the diurnal landscape of the oyster's transcriptome and pleiotropic remodeling due to toxic algae exposure, revealing the intrinsic plasticity of the cycling transcriptome in oysters.

  10. Nonlinear Dynamics and Analysis of Intracranial Saccular Aneurysms with Growth and Remodeling

    Directory of Open Access Journals (Sweden)

    Manal Badgaish


    Full Text Available A new mathematical model for the interaction of blood flow with the arterial wall surrounded by cerebral spinal fluid is developed with applications to intracranial saccular aneurysms. The blood pressure acting on the inner arterial wall is modeled via a Fourier series, the arterial wall is modeled as a spring-mass system incorporating growth and remodeling, and the surrounding cerebral spinal fluid is modeled via a simplified one-dimensional compressible Euler equation with inviscid flow and negligible nonlinear effects. The resulting nonlinear coupled fluid-structure interaction problem is analyzed and a perturbation technique is employed to derive the first-order approximation solution to the system. An analytical solution is also derived for the linearized version of the problem using Laplace transforms. The solutions are validated against related work from the literature and the results suggest the biological significance of the inclusion of the growth and remodeling effects on the rupture of intracranial aneurysms.

  11. Role of gelatinases MMP-2 and MMP-9 in tissue remodeling following acute lung injury

    Directory of Open Access Journals (Sweden)

    Corbel M.


    Full Text Available Acute lung injury is characterized by a severe disruption of alveolo-capillary structures and includes a variety of changes in lung cell populations. Evidence suggests the occurrence of rupture of the basement membranes and interstitial matrix remodeling during acute lung injury. The dynamic equilibrium of the extracellular matrix (ECM under physiological conditions is a consequence of the balance between the regulation of synthesis and degradation of ECM components. Matrix metalloproteinases (MMPs represent a group of enzymes involved in the degradation of most of the components of the ECM and therefore participate in tissue remodeling associated with pathological situations such as acute lung injury. MMP activity is regulated by proteolytic activation of the latent secreted proenzyme and by interaction with specific tissue inhibitors of metalloproteinases. This review details our knowledge of the involvement of MMPs, namely MMP-2 and MMP-9, in acute lung injury and acute respiratory distress syndrome.

  12. Cosmetic Remodeling of the Smile: Combining Composite Resin and Ceramics over Teeth and Implants

    Directory of Open Access Journals (Sweden)

    Leonardo Fernandes da Cunha


    Full Text Available The aim of this paper is to describe a restorative approach to the cosmetic remodeling of the teeth of a young adult patient with right maxillary lateral hypodontia and left lateral microdontia. A conservative restorative management was proposed to improve smile esthetics by combining direct composite resins and ceramics. Initially, periodontal therapy and dental bleaching were performed. Subsequently, direct composite resins were applied to the central incisors and canines to reestablish the sizes and shapes of these teeth. Finally, ceramics were placed on the implant and the microdontia to unite with the new alignment and color of the anterior teeth. Thus, conservative remodeling to improve the harmony of the smile was provided.

  13. Growth and Remodeling in Blood Vessels Studied In Vivo With Fractal Analysis (United States)

    Parsons-Wingerter, Patricia A.


    Every cell in the human body must reside in close proximity to a blood vessel (within approximately 200 mm) because blood vessels provide the oxygen, metabolite, and fluid exchanges required for cellular existence. The growth and remodeling of blood vessels are required to support the normal physiology of embryonic development, reproductive biology, wound healing and adaptive remodeling to exercise, as well as abnormal tissue change in diseases such as cancer, diabetes, and coronary heart disease. Cardiovascular and hemodynamic (blood flow dynamics) alterations experienced by astronauts during long-term spaceflight, including orthostatic intolerance, fluid shifts in the body, and reduced numbers of red (erythrocyte) and white (immune) blood cells, are identified as risk factors of very high priority in the NASA task force report on risk reduction for human spaceflight, the "Critical Path Roadmap."

  14. Calpain 3 is a rapid-action, unidirectional proteolytic switch central to muscle remodeling. (United States)

    de Morrée, Antoine; Lutje Hulsik, David; Impagliazzo, Antonietta; van Haagen, Herman H H B M; de Galan, Paula; van Remoortere, Alexandra; 't Hoen, Peter A C; van Ommen, Gertjan B; Frants, Rune R; van der Maarel, Silvère M


    Calpain 3 (CAPN3) is a cysteine protease that when mutated causes Limb Girdle Muscular Dystrophy 2A. It is thereby the only described Calpain family member that genetically causes a disease. Due to its inherent instability little is known of its substrates or its mechanism of activity and pathogenicity. In this investigation we define a primary sequence motif underlying CAPN3 substrate cleavage. This motif can transform non-related proteins into substrates, and identifies >300 new putative CAPN3 targets. Bioinformatic analyses of these targets demonstrate a critical role in muscle cytoskeletal remodeling and identify novel CAPN3 functions. Among the new CAPN3 substrates are three E3 SUMO ligases of the Protein Inhibitor of Activated Stats (PIAS) family. CAPN3 can cleave PIAS proteins and negatively regulates PIAS3 sumoylase activity. Consequently, SUMO2 is deregulated in patient muscle tissue. Our study thus uncovers unexpected crosstalk between CAPN3 proteolysis and protein sumoylation, with strong implications for muscle remodeling.

  15. Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities. (United States)

    Fiorini, Francesca; Bagchi, Debjani; Le Hir, Hervé; Croquette, Vincent


    RNA helicases are implicated in most cellular RNA-dependent events. In eukaryotes however, only few have been functionally characterized. Upf1 is a RNA helicase essential for nonsense-mediated mRNA decay (NMD). Here, using magnetic tweezers and bulk assays, we observe that human Upf1 is able to translocate slowly over long single-stranded nucleic acids with a processivity >10 kb. Upf1 efficiently translocates through double-stranded structures and protein-bound sequences, demonstrating that Upf1 is an efficient ribonucleoprotein complex remodeler. Our observation of processive unwinding by an eukaryotic RNA helicase reveals that Upf1, once recruited onto NMD mRNA targets, can scan the entire transcript to irreversibly remodel the mRNP, facilitating its degradation by the NMD machinery.

  16. The Post-Myocardial Infarction Pacing Remodeling Prevention Therapy (PRomPT) Trial

    DEFF Research Database (Denmark)

    Chung, Eugene S; Fischer, Trent M; Kueffer, Fred


    BACKGROUND: Despite considerable improvements in the medical management of patients with myocardial infarction (MI), patients with large MI still have substantial risk of developing heart failure. In the early post-MI setting, implantable cardioverter defibrillators have reduced arrhythmic deaths...... but have no impact on overall mortality. Therefore, additional interventions are required to further reduce the overall morbidity and mortality of patients with large MI. METHODS: The Pacing Remodeling Prevention Therapy (PRomPT) trial is designed to study the effects of peri-infarct pacing in preventing...... adverse post-MI remodeling. Up to 120 subjects with peak creatine phosphokinase >3,000 U/L (or troponin T >10 μg/L) at time of MI will be randomized to either dual-site or single-site biventricular pacing with the left ventricular lead implanted in a peri-infarct region or to a nonimplanted control group...

  17. Actomyosin pulsation and flows in an active elastomer with turnover and network remodeling. (United States)

    Banerjee, Deb Sankar; Munjal, Akankshi; Lecuit, Thomas; Rao, Madan


    Tissue remodeling requires cell shape changes associated with pulsation and flow of the actomyosin cytoskeleton. Here we describe the hydrodynamics of actomyosin as a confined active elastomer with turnover of its components. Our treatment is adapted to describe the diversity of contractile dynamical regimes observed in vivo. When myosin-induced contractile stresses are low, the deformations of the active elastomer are affine and exhibit spontaneous oscillations, propagating waves, contractile collapse and spatiotemporal chaos. We study the nucleation, growth and coalescence of actomyosin-dense regions that, beyond a threshold, spontaneously move as a spatially localized traveling front. Large myosin-induced contractile stresses lead to nonaffine deformations due to enhanced actin and crosslinker turnover. This results in a transient actin network that is constantly remodeling and naturally accommodates intranetwork flows of the actomyosin-dense regions. We verify many predictions of our study in Drosophila embryonic epithelial cells undergoing neighbor exchange during germband extension.

  18. A supra-cellular model for coupling of bone resorption to formation during remodeling

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L


    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the ost......The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released...... osteoblasts from the canopy is induced by osteoclastic factors, thereby favoring initiation of bone formation. They lead to a model where the osteoclast-canopy interface is the physical site where coupling of bone resorption to bone formation occurs....

  19. Identification, replication and characterization of epigenetic remodelling in the aging genome

    DEFF Research Database (Denmark)

    Li, Shuxia; Christiansen, Lene; Christensen, Kaare

    Background: Aging is a complex biological process that involves numerous changes at various levels through remodelling of multiple biological processes and regulatory mechanisms including epigenetics. Recent analysis of the DNA methylome has reported large numbers of epigenetic markers associated...... with human aging. Validation and characterization of the significant findings are necessary both for obtaining reliable results and for better describing the age-associated epigenetic modifications. Methods: Based on genome-wide DNA methylation data measured in a large collection of older individuals....... Conclusion: Extensive epigenetic remodelling in the DNA methylome could be involved in the aging process. The identified age-methylated and demethylated sites displayed differential distribution patterns over genomic regions and were involved in biological pathways closely related to aging phenotypes and age...

  20. Adolescent alcohol exposure: Burden of epigenetic reprogramming, synaptic remodeling, and adult psychopathology

    Directory of Open Access Journals (Sweden)

    Evan J Kyzar


    Full Text Available Adolescence represents a crucial phase of synaptic maturation characterized by molecular changes in the developing brain that shape normal behavioral patterns. Epigenetic mechanisms play an important role in these neuromaturation processes. Perturbations of normal epigenetic programming during adolescence by ethanol can delay these molecular events, leading to synaptic remodeling and abnormal adult behaviors. Repeated exposure to binge levels of alcohol increases the risk for alcohol use disorder (AUD and comorbid psychopathology including anxiety in adulthood. Recent studies in the field clearly suggest that adolescent alcohol exposure causes widespread and persistent changes in epigenetic, neurotrophic, and neuroimmune pathways in the brain. These changes are manifested by altered synaptic remodeling and neurogenesis in key brain regions leading to adult psychopathology such as anxiety and alcoholism. This review details the molecular mechanisms underlying adolescent alcohol exposure-induced changes in synaptic plasticity and the development of alcohol addiction-related phenotypes in adulthood.