Tunable deformation modes shape contractility in active biopolymer networks

NASA Astrophysics Data System (ADS)

Stam, Samantha; Banerjee, Shiladitya; Weirich, Kim; Freedman, Simon; Dinner, Aaron; Gardel, Margaret

Biological polymer-based materials remodel under active, molecular motor-driven forces to perform diverse physiological roles, such as force transmission and spatial self-organization. Critical to understanding these biomaterials is elucidating the role of microscopic polymer deformations, such as stretching, bending, buckling, and relative sliding, on material remodeling. Here, we report that the shape of motor-driven deformations can be used to identify microscopic deformation modes and determine how they propagate to longer length scales. In cross-linked actin networks with sufficiently low densities of the motor protein myosin II, microscopic network deformations are predominantly uniaxial, or dominated by sliding. However, longer-wavelength modes are mostly biaxial, or dominated by bending and buckling, indicating that deformations with uniaxial shapes do not propagate across length scales significantly larger than that of individual polymers. As the density of myosin II is increased, biaxial modes dominate on all length scales we examine due to buildup of sufficient stress to produce smaller-wavelength buckling. In contrast, when we construct networks from unipolar, rigid actin bundles, we observe uniaxial, sliding-based contractions on 1 to 100 μm length scales. Our results demonstrate the biopolymer mechanics can be used to tune deformation modes which, in turn, control shape changes in active materials.

Stimulated Emission Depletion Nanoscopy Reveals Time-Course of Human Immunodeficiency Virus Proteolytic Maturation.

PubMed

Hanne, Janina; Göttfert, Fabian; Schimer, Jiří; Anders-Össwein, Maria; Konvalinka, Jan; Engelhardt, Johann; Müller, Barbara; Hell, Stefan W; Kräusslich, Hans-Georg

2016-09-27

Concomitant with human immunodeficiency virus type 1 (HIV-1) budding from a host cell, cleavage of the structural Gag polyproteins by the viral protease (PR) triggers complete remodeling of virion architecture. This maturation process is essential for virus infectivity. Electron tomography provided structures of immature and mature HIV-1 with a diameter of 120-140 nm, but information about the sequence and dynamics of structural rearrangements is lacking. Here, we employed super-resolution STED (stimulated emission depletion) fluorescence nanoscopy of HIV-1 carrying labeled Gag to visualize the virion architecture. The incomplete Gag lattice of immature virions was clearly distinguishable from the condensed distribution of mature protein subunits. Synchronized activation of PR within purified particles by photocleavage of a caged PR inhibitor enabled time-resolved in situ observation of the induction of proteolysis and maturation by super-resolution microscopy. This study shows the rearrangement of subviral structures in a super-resolution light microscope over time, outwitting phototoxicity and fluorophore bleaching through synchronization of a biological process by an optical switch.

Biophysical Properties and Motility of Human Mature Dendritic Cells Deteriorated by Vascular Endothelial Growth Factor through Cytoskeleton Remodeling

PubMed Central

Hu, Zu-Quan; Xue, Hui; Long, Jin-Hua; Wang, Yun; Jia, Yi; Qiu, Wei; Zhou, Jing; Wen, Zong-Yao; Yao, Wei-Juan; Zeng, Zhu

2016-01-01

Dendritic cells (DCs), the most potent antigen-presenting cells, play a central role in the initiation, regulation, and maintenance of the immune responses. Vascular endothelial growth factor (VEGF) is one of the important cytokines in the tumor microenvironment (TME) and can inhibit the differentiation and functional maturation of DCs. To elucidate the potential mechanisms of DC dysfunction induced by VEGF, the effects of VEGF on the biophysical characteristics and motility of human mature DCs (mDCs) were investigated. The results showed that VEGF had a negative influence on the biophysical properties, including electrophoretic mobility, osmotic fragility, viscoelasticity, and transmigration. Further cytoskeleton structure analysis by confocal microscope and gene expression profile analyses by gene microarray and real-time PCR indicated that the abnormal remodeling of F-actin cytoskeleton may be the main reason for the deterioration of biophysical properties, motility, and stimulatory capability of VEGF-treated mDCs. This is significant for understanding the biological behavior of DCs and the immune escape mechanism of tumors. Simultaneously, the therapeutic efficacies may be improved by blocking the signaling pathway of VEGF in an appropriate manner before the deployment of DC-based vaccinations against tumors. PMID:27809226

Impact of aldosterone antagonists on the substrate for atrial fibrillation: Aldosterone promotes oxidative stress and atrial structural/electrical remodeling

PubMed Central

Mayyas, Fadia; Alzoubi, Karem H.; Van Wagoner, David R.

2014-01-01

Atrial fibrillation (AF), the most common cardiac arrhythmia, is an electrocardiographic description of a condition with multiple and complex underlying mechanisms. Oxidative stress is an important driver of structural remodeling that creates a substrate for AF. Oxidant radicals may promote increase of atrial oxidative damage, electrical and structural remodeling, and atrial inflammation. AF and other cardiovascular morbidities activate angiotensin (Ang-II)-dependent and independent cascades. A key component of the renin–angiotensin-aldosterone system (RAAS) is the mineralocorticoid aldosterone. Recent studies provide evidence of myocardial aldosterone synthesis. Aldosterone promotes cardiac oxidative stress, inflammation and structural/electrical remodeling via multiple mechanisms. In HF patients, aldosterone production is enhanced. In patients and in experimental HF and AF models, aldosterone receptor antagonists have favorable influences on cardiac remodeling and oxidative stress. Therapeutic approaches that seek to reduce AF burden by modulating the aldosterone system are likely beneficial but underutilized. PMID:23993726

Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse RemodelingCLINICAL PERSPECTIVE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kali, Avinash; Cokic, Ivan; Tang, Richard

Emerging evidence now supports the notion that persistent microvascular obstruction (PMO) may be more predictive of major adverse cardiovascular events than MI size itself. But, how PMO, a phenomenon limited to the acute/sub-acute period of MI, imparts adverse remodeling throughout the post MI period, particularly after its resolution, is incompletely understood. We hypothesized that PMOs resolve into chronic iron crystals within MI territories and actively impart a proinflammatory burden and adverse remodeling of infarction and LV in the chronic phase of MI. Canine models reperfused (n=20) and non-reperfused (n=20) with and without PMO were studied with serial cardiac MRI tomore » characterize the spatiotemporal relationships between PMO, iron deposition, and infarct and LV remodeling indices between acute (day 7, post MI) and chronic (week 8, post MI). Histopathology and immunohistochemistry were used to validate the iron deposition, microscopically map and quantify the relationship between iron-rich chronic MI regions against pro-inflammatory macrophages, proinflammatory cytokines and matrix metalloproteinase. Atomic resolution transmission electron microscopy (TEM) was used to determine the crystallinity of iron and assess the physical effects of iron on lysosomes within macrophages, and energy-dispersive X-ray spectroscopy (EDS) to identify the chemical composition of the iron composite. Results showed that PMOs lead to iron deposition within chronic MI and that the extent of chronic iron deposition is strongly related to PMO Volume (r>0.6, p<0.001). TEM and EDS analysis showed that iron within chronic MI is found within macrophages as aggregates of nanocrystals of ~2.5 nm diameter in ferric state. Correlative histological studies showed that iron content, proinflammatory burden and collagen degrading enzyme were highly correlated (r >0.7, p<0.001). Iron within chronic MI was significantly associated with infarct resorption (r>0.5, p<0.001) and adverse structural (r>0.5, p<0.001) remodeling. Territories of PMO in the acute phase of MI resolve into iron oxide nanocrystals in ferric state in the chronic phase of MI. The amount of iron deposition is determined by the extent of persistent microvascular obstruction and is directly related to the extent of pro-inflammatory burden, infarct thinning and adverse LV remodeling. Resolution of PMO into iron deposition could be a potential contributing source to the adverse remodeling of the heart in the chronic phase of MI.« less

Novel insights on the relationship between T-tubular defects and contractile dysfunction in a mouse model of hypertrophic cardiomyopathy.

PubMed

Crocini, C; Ferrantini, C; Scardigli, M; Coppini, R; Mazzoni, L; Lazzeri, E; Pioner, J M; Scellini, B; Guo, A; Song, L S; Yan, P; Loew, L M; Tardiff, J; Tesi, C; Vanzi, F; Cerbai, E; Pavone, F S; Sacconi, L; Poggesi, C

2016-02-01

Abnormalities of cardiomyocyte Ca(2+) homeostasis and excitation-contraction (E-C) coupling are early events in the pathogenesis of hypertrophic cardiomyopathy (HCM) and concomitant determinants of the diastolic dysfunction and arrhythmias typical of the disease. T-tubule remodelling has been reported to occur in HCM but little is known about its role in the E-C coupling alterations of HCM. Here, the role of T-tubule remodelling in the electro-mechanical dysfunction associated to HCM is investigated in the Δ160E cTnT mouse model that expresses a clinically-relevant HCM mutation. Contractile function of intact ventricular trabeculae is assessed in Δ160E mice and wild-type siblings. As compared with wild-type, Δ160E trabeculae show prolonged kinetics of force development and relaxation, blunted force-frequency response with reduced active tension at high stimulation frequency, and increased occurrence of spontaneous contractions. Consistently, prolonged Ca(2+) transient in terms of rise and duration are also observed in Δ160E trabeculae and isolated cardiomyocytes. Confocal imaging in cells isolated from Δ160E mice reveals significant, though modest, remodelling of T-tubular architecture. A two-photon random access microscope is employed to dissect the spatio-temporal relationship between T-tubular electrical activity and local Ca(2+) release in isolated cardiomyocytes. In Δ160E cardiomyocytes, a significant number of T-tubules (>20%) fails to propagate action potentials, with consequent delay of local Ca(2+) release. At variance with wild-type, we also observe significantly increased variability of local Ca(2+) transient rise as well as higher Ca(2+)-spark frequency. Although T-tubule structural remodelling in Δ160E myocytes is modest, T-tubule functional defects determine non-homogeneous Ca(2+) release and delayed myofilament activation that significantly contribute to mechanical dysfunction. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structural pathways and prevention of heart failure and sudden death.

PubMed

Pacifico, Antonio; Henry, Philip D

2003-07-01

We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5- to 6-fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose-dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express "fetospecific" genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up-regulation of the adrenergic renin-angiotensin-aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel-active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing-induced remodeling decreases left ventricular mass remains uncertain.

Brownian movement and microscopic irreversibility

NASA Astrophysics Data System (ADS)

Gordon, L. G. M.

1981-02-01

An extension of the hypothetical experiment of Szilard, which involved the action of a one-molecule gas in an isolated isothermal system, is developed to illustrate how irreversibility may arise out of Brownian motion. As this development requires a consideration of nonmolecular components such as wheels and pistons, the thought-experiment is remodeled in molecular terms and appears to function as a perpetuum mobile.

Micro-structurally detailed model of a therapeutic hydrogel injectate in a rat biventricular cardiac geometry for computational simulations

PubMed Central

Sirry, Mazin S.; Davies, Neil H.; Kadner, Karen; Dubuis, Laura; Saleh, Muhammad G.; Meintjes, Ernesta M.; Spottiswoode, Bruce S.; Zilla, Peter; Franz, Thomas

2013-01-01

Biomaterial injection based therapies have showed cautious success in restoration of cardiac function and prevention of adverse remodelling into heart failure after myocardial infarction (MI). However, the underlying mechanisms are not well understood. Computational studies utilised simplified representations of the therapeutic myocardial injectates. Wistar rats underwent experimental infarction followed by immediate injection of polyethylene glycol hydrogel in the infarct region. Hearts were explanted, cryo-sectioned and the region with the injectate histologically analysed. Histological micrographs were used to reconstruct the dispersed hydrogel injectate. Cardiac magnetic resonance imaging (CMRI) data from a healthy rat were used to obtain an end-diastolic biventricular geometry which was subsequently adjusted and combined with the injectate model. The computational geometry of the injectate exhibited microscopic structural details found the in situ. The combination of injectate and cardiac geometry provides realistic geometries for multiscale computational studies of intra-myocardial injectate therapies for the rat model that has been widely used for MI research. PMID:23682845

Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation.

PubMed

Tanaka, Leonardo Y; Laurindo, Francisco R M

2017-08-01

Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Matrix modulation and heart failure: new concepts question old beliefs.

PubMed

Deschamps, Anne M; Spinale, Francis G

2005-05-01

Myocardial remodeling is a complex process involving several molecular and cellular factors. Extracellular matrix has been implicated in the remodeling process. Historically, the myocardial extracellular matrix was thought to serve solely as a means to align cells and provide structure to the tissue. Although this is one of its important functions, evidence suggests that the extracellular matrix plays a complex and divergent role in influencing cell behavior. This paper characterizes some of the notable studies on this dynamic entity and on adverse myocardial remodeling that have been published over the past year, which further question the belief that the extracellular matrix is a static structure. Progress has been made in understanding how the extracellular matrix is operative in the three major conditions (myocardial infarction, left ventricular hypertrophy due to overload, and dilated cardiomyopathy) that involve myocardial remodeling. Several studies have examined plasma profiles of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases following myocardial infarction and during left ventricular hypertrophy as surrogate markers of remodeling/remodeled myocardium. It has been demonstrated that bioactive signaling molecules and growth factors, proteases, and structural proteins influence cell-matrix interactions in the context of left ventricular hypertrophy. Finally, studies that either removed or added tissue inhibitor of metalloproteinases species in the myocardium demonstrated the importance of this regulatory protein in the remodeling process. Understanding the cellular and molecular triggers that in turn give rise to changes in the extracellular matrix could provide opportunities to modify the remodeling process.

Inflammatory Mediators Drive Adverse Right Ventricular Remodeling and Dysfunction and Serve as Potential Biomarkers.

PubMed

Sydykov, Akylbek; Mamazhakypov, Argen; Petrovic, Aleksandar; Kosanovic, Djuro; Sarybaev, Akpay S; Weissmann, Norbert; Ghofrani, Hossein A; Schermuly, Ralph T

2018-01-01

Adverse right ventricular (RV) remodeling leads to ventricular dysfunction and failure that represents an important determinant of outcome in patients with pulmonary hypertension (PH). Recent evidence indicates that inflammatory activation contributes to the pathogenesis of adverse RV remodeling and dysfunction. It has been shown that accumulation of inflammatory cells such as macrophages and mast cells in the right ventricle is associated with maladaptive RV remodeling. In addition, inhibition of inflammation in animal models of RV failure ameliorated RV structural and functional impairment. Furthermore, a number of circulating inflammatory mediators have been demonstrated to be associated with RV performance. This work reviews the role of inflammation in RV remodeling and dysfunction and discusses anti-inflammatory strategies that may attenuate adverse structural alterations while promoting improvement of RV function.

Inflammatory Mediators Drive Adverse Right Ventricular Remodeling and Dysfunction and Serve as Potential Biomarkers

PubMed Central

Sydykov, Akylbek; Mamazhakypov, Argen; Petrovic, Aleksandar; Kosanovic, Djuro; Sarybaev, Akpay S.; Weissmann, Norbert; Ghofrani, Hossein A.; Schermuly, Ralph T.

2018-01-01

Adverse right ventricular (RV) remodeling leads to ventricular dysfunction and failure that represents an important determinant of outcome in patients with pulmonary hypertension (PH). Recent evidence indicates that inflammatory activation contributes to the pathogenesis of adverse RV remodeling and dysfunction. It has been shown that accumulation of inflammatory cells such as macrophages and mast cells in the right ventricle is associated with maladaptive RV remodeling. In addition, inhibition of inflammation in animal models of RV failure ameliorated RV structural and functional impairment. Furthermore, a number of circulating inflammatory mediators have been demonstrated to be associated with RV performance. This work reviews the role of inflammation in RV remodeling and dysfunction and discusses anti-inflammatory strategies that may attenuate adverse structural alterations while promoting improvement of RV function. PMID:29875701

Remodeling of the transverse tubular system after myocardial infarction in rabbit correlates with local fibrosis: A potential role of biomechanics.

PubMed

Seidel, T; Sankarankutty, A C; Sachse, F B

2017-11-01

The transverse tubular system (t-system) of ventricular cardiomyocytes is essential for efficient excitation-contraction coupling. In cardiac diseases, such as heart failure, remodeling of the t-system contributes to reduced cardiac contractility. However, mechanisms of t-system remodeling are incompletely understood. Prior studies suggested an association with altered cardiac biomechanics and gene expression in disease. Since fibrosis may alter tissue biomechanics, we investigated the local microscopic association of t-system remodeling with fibrosis in a rabbit model of myocardial infarction (MI). Biopsies were taken from the MI border zone of 6 infarcted hearts and from 6 control hearts. Using confocal microscopy and automated image analysis, we quantified t-system integrity (I TT ) and the local fraction of extracellular matrix (f ECM ). In control, f ECM was 18 ± 0.3%. I TT was high and homogeneous (0.07 ± 0.006), and did not correlate with f ECM (R 2  = 0.05 ± 0.02). The MI border zone exhibited increased f ECM within 3 mm from the infarct scar (30 ± 3.5%, p < 0.01 vs control), indicating fibrosis. Myocytes in the MI border zone exhibited significant t-system remodeling, with dilated, sheet-like components, resulting in low I TT (0.03 ± 0.008, p < 0.001 vs control). While both f ECM and t-system remodeling decreased with infarct distance, I TT correlated better with decreasing f ECM (R 2  = 0.44) than with infarct distance (R 2  = 0.24, p < 0.05). Our results show that t-system remodeling in the rabbit MI border zone resembles a phenotype previously described in human heart failure. T-system remodeling correlated with the amount of local fibrosis, which is known to stiffen cardiac tissue, but was not found in regions without fibrosis. Thus, locally altered tissue mechanics may contribute to t-system remodeling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of maternal folic acid supplementation on airway remodeling and allergic airway disease development.

PubMed

İscan, Burcin; Tuzun, Funda; Eroglu Filibeli, Berna; Cilekar Micili, Serap; Ergur, Bekir Ugur; Duman, Nuray; Ozkan, Hasan; Kumral, Abdullah

2018-03-27

Maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy to reduce the risk of infant neural tube defects. However, an uncertain relationship between folic acid supplementation during pregnancy and development of childhood asthma exists. Recent data show a methyl donor-rich diet could increase the risk of developing allergic airway disease through DNA methylation and aberrant gene transcription. This study evaluated the effect of folic acid supplementation during pregnancy on airway remodeling and allergic airway disease vulnerability in a mouse asthma model. BALB/c mice were divided into four groups according to gestational folic acid supplementation and postnatal ovalbumin (OVA) exposure: Group 1 (whole pregnancy folic acid supplementation + OVA-exposed group), Group 2 (first gestational week folic acid supplementation + OVA-exposed group), Group 3 (no folic acid supplementation + OVA-exposed group), and Group 4 (control group). Offspring were sacrificed on day 45 for immunohistological and ultrastructural tests. In OVA challenged groups, folic acid supplementation led to a thicker epithelial and subepithelial smooth muscle layer than in the unsupplemented group. Moreover, folic acid supplementation during whole pregnancy (Group 1) was associated with a thicker epithelial and subepithelial smooth muscle layer than folic acid supplementation during the first week of pregnancy (Group 2), suggesting a duration-response relationship. Electron microscopic imaging revealed that structural changes including the loss of epithelial integrity, thickening of basement membrane, and subepithelial fibrosis were more prominent in the folic acid supplementation groups. This study suggested that maternal folic acid supplementation during pregnancy affects airway remodeling and increases the allergic responses induced by ovalbumin challenge in offspring. In addition, the effect size increased as the duration and cumulative dose increased.

Remodelling the extracellular matrix in development and disease

PubMed Central

Bonnans, Caroline; Chou, Jonathan; Werb, Zena

2015-01-01

The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes that are responsible for ECM degradation, such as metalloproteinases. The ECM interacts with cells to regulate diverse functions, including proliferation, migration and differentiation. ECM remodelling is crucial for regulating the morphogenesis of the intestine and lungs, as well as of the mammary and submandibular glands. Dysregulation of ECM composition, structure, stiffness and abundance contributes to several pathological conditions, such as fibrosis and invasive cancer. A better understanding of how the ECM regulates organ structure and function and of how ECM remodelling affects disease progression will contribute to the development of new therapeutics. PMID:25415508

RosettaRemodel: A Generalized Framework for Flexible Backbone Protein Design

PubMed Central

Huang, Po-Ssu; Ban, Yih-En Andrew; Richter, Florian; Andre, Ingemar; Vernon, Robert; Schief, William R.; Baker, David

2011-01-01

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. PMID:21909381

Profilin-1 Promotes the Development of Hypertension-induced Artery Remodeling

PubMed Central

Wang, Yan; Zhang, Jun; Gao, Haiqing; Zhao, Shaohua; Ji, Xiang; Liu, Xiangju; You, Beian; Li, Xiao

2014-01-01

Hypertension is associated with the structural remodeling and stiffening of arteries and is known to increase cardiovascular risk. In the present study, we investigated the effects of overexpression and knock down of profilin-1 on the vascular structural remodeling in spontaneous hypertensive rats (SHRs) using an adenovirus injection to knock down or overexpress profilin-1 mRNA. As a control, blank adenovirus was injected into age-matched SHRs and Wistar-Kyoto rats (WKYs). We quantified arterial structural remodeling through morphological methods, with thoracic aortas stained with hematoxylin–eosin and picosirius red. Western blotting was performed to measure the protein expression of inducible nitric oxide synthase (iNOS) and p38 mitogen-activated protein kinase (p38), and peroxynitrite was quantified by immunohistochemical staining. Overexpression of profilin-1 significantly promoted aortic remodeling, including an increase in vessel size, wall thickness, and collagen content, whereas the knockdown of profilin-1 could reverse these effects. In addition, the expression of phosphorylated p38, iNOS and peroxynitrite was significantly upregulated in SHRs with profilin-1 overexpression along with an increased level of interleukin- 6 (IL-6). These changes could be reversed by knockdown of profilin-1. Our results demonstrate a crucial role for profilin-1 in hypertension-induced arterial structural remodeling at least in part through the p38–iNOS–peroxynitrite pathway. PMID:24399041

Transforming Growth Factor β1 Function in Airway Remodeling and Hyperresponsiveness. The Missing Link?

PubMed

Ojiaku, Christie A; Yoo, Edwin J; Panettieri, Reynold A

2017-04-01

The pathogenesis of asthma includes a complex interplay among airway inflammation, hyperresponsiveness, and remodeling. Current evidence suggests that airway structural cells, including bronchial smooth muscle cells, myofibroblasts, fibroblasts, and epithelial cells, mediate all three aspects of asthma pathogenesis. Although studies show a connection between airway remodeling and changes in bronchomotor tone, the relationship between the two remains unclear. Transforming growth factor β1 (TGF-β1), a growth factor elevated in the airway of patients with asthma, plays a role in airway remodeling and in the shortening of various airway structural cells. However, the role of TGF-β1 in mediating airway hyperresponsiveness remains unclear. In this review, we summarize the literature addressing the role of TGF-β1 in airway remodeling and shortening. Through our review, we aim to further elucidate the role of TGF-β1 in asthma pathogenesis and the link between airway remodeling and airway hyperresponsiveness in asthma and to define TGF-β1 as a potential therapeutic target for reducing asthma morbidity and mortality.

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

PubMed Central

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

2015-01-01

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) dissociates TATA box-binding protein (TBP):DNA complexes, offering a useful system to address the structural mechanisms of Swi2/Snf2 ATPases. Here, we report the crystal structure of the N-terminal domain of Mot1 in complex with TBP, DNA, and the transcription regulator negative cofactor 2 (NC2). Our data show that Mot1 reduces DNA:NC2 interactions and unbends DNA as compared to the TBP:DNA:NC2 state, suggesting that Mot1 primes TBP:NC2 displacement in an ATP-independent manner. Electron microscopy and cross-linking data suggest that the Swi2/Snf2 domain of Mot1 associates with the upstream DNA and the histone fold of NC2, thereby revealing parallels to some nucleosome remodelers. This study provides a structural framework for how a Swi2/Snf2 ATPase interacts with its substrate DNA:protein complex. DOI: http://dx.doi.org/10.7554/eLife.07432.001 PMID:26258880

Chromatin remodelling: the industrial revolution of DNA around histones.

PubMed

Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R

2006-06-01

Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

[Atrial fibrillation as consequence and cause of structural changes of atria].

PubMed

Aparina, O P; Chikhireva, L N; Stukalova, O V; Mironova, N A; Kashtanova, S Iu; Ternovoĭ, S K; Golitsyn, S P

2014-01-01

Changes of atrial structure and function are the contributors of atrial fibrillation clinical course, complications and treatment effectiveness. Effects of inflammation and mechanical stretch on atrial structural remodeling leading to atrial fibrillation are reviewed in the article. Contemporary invasive and non-invasive methods of evaluation (including late gadolinium enhancement magnetic resonance imaging) of patients with atrial structural remodeling in atrial fibrillation are also described.

A Coincidence Detection Mechanism Controls PX-BAR Domain-Mediated Endocytic Membrane Remodeling via an Allosteric Structural Switch.

PubMed

Lo, Wen-Ting; Vujičić Žagar, Andreja; Gerth, Fabian; Lehmann, Martin; Puchkov, Dymtro; Krylova, Oxana; Freund, Christian; Scapozza, Leonardo; Vadas, Oscar; Haucke, Volker

2017-11-20

Clathrin-mediated endocytosis occurs by bending and remodeling of the membrane underneath the coat. Bin-amphiphysin-rvs (BAR) domain proteins are crucial for endocytic membrane remodeling, but how their activity is spatiotemporally controlled is largely unknown. We demonstrate that the membrane remodeling activity of sorting nexin 9 (SNX9), a late-acting endocytic PX-BAR domain protein required for constriction of U-shaped endocytic intermediates, is controlled by an allosteric structural switch involving coincident detection of the clathrin adaptor AP2 and phosphatidylinositol-3,4-bisphosphate (PI(3,4)P 2 ) at endocytic sites. Structural, biochemical, and cell biological data show that SNX9 is autoinhibited in solution. Binding to PI(3,4)P 2 via its PX-BAR domain, and concomitant association with AP2 via sequences in the linker region, releases SNX9 autoinhibitory contacts to enable membrane constriction. Our results reveal a mechanism for restricting the latent membrane remodeling activity of BAR domain proteins to allow spatiotemporal coupling of membrane constriction to the progression of the endocytic pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Phospholipase Cβ1 induces membrane tubulation and is involved in caveolae formation

PubMed Central

Inaba, Takehiko; Kishimoto, Takuma; Murate, Motohide; Tajima, Takuya; Sakai, Shota; Abe, Mitsuhiro; Makino, Asami; Tomishige, Nario; Ishitsuka, Reiko; Ikeda, Yasuo; Takeoka, Shinji; Kobayashi, Toshihide

2016-01-01

Lipid membrane curvature plays important roles in various physiological phenomena. Curvature-regulated dynamic membrane remodeling is achieved by the interaction between lipids and proteins. So far, several membrane sensing/sculpting proteins, such as Bin/amphiphysin/Rvs (BAR) proteins, are reported, but there remains the possibility of the existence of unidentified membrane-deforming proteins that have not been uncovered by sequence homology. To identify new lipid membrane deformation proteins, we applied liposome-based microscopic screening, using unbiased-darkfield microscopy. Using this method, we identified phospholipase Cβ1 (PLCβ1) as a new candidate. PLCβ1 is well characterized as an enzyme catalyzing the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2). In addition to lipase activity, our results indicate that PLCβ1 possessed the ability of membrane tubulation. Lipase domains and inositol phospholipids binding the pleckstrin homology (PH) domain of PLCβ1 were not involved, but the C-terminal sequence was responsible for this tubulation activity. Computational modeling revealed that the C terminus displays the structural homology to the BAR domains, which is well known as a membrane sensing/sculpting domain. Overexpression of PLCβ1 caused plasma membrane tubulation, whereas knockdown of the protein reduced the number of caveolae and induced the evagination of caveolin-rich membrane domains. Taken together, our results suggest a new function of PLCβ1: plasma membrane remodeling, and in particular, caveolae formation. PMID:27342861

Zn deposition at the bone cartilage interface in equine articular cartilage

NASA Astrophysics Data System (ADS)

Bradley, D. A.; Moger, C. J.; Winlove, C. P.

2007-09-01

In articular cartilage metalloproteinases, a family of enzymes whose function relies on the presence of divalent cations such as Zn and Ca plays a central role in the normal processes of growth and remodelling and in the degenerative and inflammatory processes of arthritis. Another important enzyme, alkaline phosphatase, involved in cartilage mineralisation also relies on metallic cofactors. The local concentration of divalent cations is therefore of considerable interest in cartilage pathophysiology and several authors have used synchrotron X-ray fluorescence (XRF) to map metal ion distributions in bone and cartilage. We report use of a bench-top XRF analytical microscope, providing spatial resolution of 10 μm and applicable to histological sections, facilitating correlation of the distribution with structural features. The study seeks to establish the elemental distribution in normal tissue as a precursor to investigation of changes in disease. For six samples prepared from equine metacarpophalangeal joint, we observed increased concentration of Zn and Sr ions around the tidemark between normal and mineralised cartilage. This is believed to be an active site of remodelling but its composition has hitherto lacked detailed characterization. We also report preliminary results on two of the samples using Proton-Induced X-ray Emission (PIXE). This confirms our previous observations using synchrotron-based XRF of enhanced deposition of Sr and Zn at the surface of the subchondral bone and in articular cartilage.

Bone remodelling: its local regulation and the emergence of bone fragility.

PubMed

Martin, T John; Seeman, Ego

2008-10-01

Bone modelling prevents the occurrence of damage by adapting bone structure - and hence bone strength - to its loading circumstances. Bone remodelling removes damage, when it inevitably occurs, in order to maintain bone strength. This cellular machinery is successful during growth, but fails during advancing age because of the development of a negative balance between the volumes of bone resorbed and formed during remodelling by the basic multicellular unit (BMU), high rates of remodelling during midlife in women and late in life in both sexes, and a decline in periosteal bone formation. together resulting in bone loss and structural decay each time a remodelling event occurs. The two steps in remodelling - resorption of a volume of bone by osteoclasts and formation of a comparable volume by osteoblasts - are sequential, but the regulatory events leading to these two fully differentiated functions are not. Reparative remodelling is initiated by damage producing osteocyte apoptosis, which signals the location of damage via the osteocyte canalicular system to endosteal lining cells which forms the canopy of a bone-remodelling compartment (BRC). Within the BRC, local recruitment of osteoblast precursors from the lining cells, the marrow and circulation, direct contact with osteoclast precursors, osteoclastogenesis and molecular cross-talk between precursors, mature cells, cells of the immune system, and products of the resorbed matrix, titrate the birth, work and lifespan of the cells of this multicellular remodelling machinery to either remove or form a net volume of bone appropriate to the mechanical requirements.

The HVAC Challenges of Upgrading an Old Lab for High-end Light Microscopes

PubMed Central

Richard, R.; Martone, P.; Callahan, L.M.

2014-01-01

The University of Rochester Medical Center forms the centerpiece of the University of Rochester's health research, teaching, patient care, and community outreach missions. Within this large facility of over 5 million square feet, demolition and remodeling of existing spaces is a constant activity. With more than $145 million in federal research funding, lab space is frequently repurposed and renovated to support this work. The URMC Medical Center Facilities Organization supporting small to medium space renovations is constantly challenged and constrained by the existing mechanical infrastructure and budgets to deliver a renovated space that functions within the equipment environmental parameters. One recent project, sponsored by the URMC Shared Resources Laboratory, demonstrates these points. The URMC Light Microscopy Shared Resource Laboratory requested renovation of a 121 sq. ft. room in a 40 year old building which would enable placement of a laser capture microdissection microscope and a Pascal 5 laser scanning confocal microscope with the instruments separated by a blackout curtain. This poster discusses the engineering approach implemented to bring an older lab into the environmental specifications needed for the proper operation of the high-end light microscopes.

The Chromatin Remodeler SPLAYED Regulates Specific Stress Signaling Pathways

PubMed Central

Walley, Justin W.; Rowe, Heather C.; Xiao, Yanmei; Chehab, E. Wassim; Kliebenstein, Daniel J.; Wagner, Doris; Dehesh, Katayoon

2008-01-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks. PMID:19079584

The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

PubMed

Walley, Justin W; Rowe, Heather C; Xiao, Yanmei; Chehab, E Wassim; Kliebenstein, Daniel J; Wagner, Doris; Dehesh, Katayoon

2008-12-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

Cell Mechanisms of Bone Tissue Loss Under Space Flight Conditions

NASA Astrophysics Data System (ADS)

Rodionova, Natalia

Investigations on the space biosatellites has shown that the bone skeleton is one of the most im-portant targets of the effect space flight factors on the organism. Bone tissue cells were studied by electron microscopy in biosamples of rats' long bones flown on the board american station "SLS-2" and in experiments with modelling of microgravity ("tail suspension" method) with using autoradiography. The analysis of data permits to suppose that the processes of remod-eling in bone tissue at microgravity include the following succession of cell-to-cell interactions. Osteocytes as mechanosensory cells are first who respond to a changing "mechanical field". The next stage is intensification of osteolytic processes in osteocytes, leading to a volume en-largement of the osteocytic lacunae and removal of the "excess bone". Then mechanical signals have been transmitted through a system of canals and processes of the osteocytic syncitium to certain superficial bone zones and are perceived by osteoblasts and bone-lining cells (superficial osteocytes), as well as by the bone-marrow stromal cells. The sensitivity of stromal cells, pre-osteoblasts and osteoblasts, under microgravity was shown in a number of works. As a response to microgravity, the system of stromal cells -preosteoblasts -osteoblasts displays retardation of proliferation, differentiation and specific functions of osteogenetic cells. This is supported by the 3H-thymidine studies of the dynamics of differentiation of osteogenetic cells in remodeling zones. But unloading is not adequate and in part of the osteocytes are apoptotic changes as shown by our electron microscopic investigations. An osteocytic apoptosis can play the role in attraction the osteoclasts and in regulation of bone remodeling. The apoptotic bodies with a liquid flow through a system of canals are transferred to the bone surface, where they fulfil the role of haemoattractants for monocytes come here and form osteoclasts. The osteoclasts destroy bone tissue. The macrophages are incorporated into resorption lacunaes and utilize the organic matrix and cellular detritus. The products are secreted to remodeling zones and act as haemoattractants for recruiting and subsequent differentiation here of the osteogenic precursor cells. However, as shown by our results with 3H-glycine, in absence of mechanical stimulus the activization of osteoblastogenesis either doesn't occur, or takes place on a smaller scale. According to our electron-microscopic data a load deficit leads to an adaptive differentiation of fibroblasts and adipocytes in this remodeling zones. This sequence of events is considered as a mechanism of bone tissue loss which underlies the development of osteopenia and osteoporosis under space flight condition.

Organization and dynamics of the actin cytoskeleton during dendritic spine morphological remodeling.

PubMed

Chazeau, Anaël; Giannone, Grégory

2016-08-01

In the central nervous system, most excitatory post-synapses are small subcellular structures called dendritic spines. Their structure and morphological remodeling are tightly coupled to changes in synaptic transmission. The F-actin cytoskeleton is the main driving force of dendritic spine remodeling and sustains synaptic plasticity. It is therefore essential to understand how changes in synaptic transmission can regulate the organization and dynamics of actin binding proteins (ABPs). In this review, we will provide a detailed description of the organization and dynamics of F-actin and ABPs in dendritic spines and will discuss the current models explaining how the actin cytoskeleton sustains both structural and functional synaptic plasticity.

DNA repair goes hip-hop: SMARCA and CHD chromatin remodellers join the break dance.

PubMed

Rother, Magdalena B; van Attikum, Haico

2017-10-05

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.

Membrane remodeling by amyloidogenic and non-amyloidogenic proteins studied by EPR

NASA Astrophysics Data System (ADS)

Varkey, Jobin; Langen, Ralf

2017-07-01

The advancement in site-directed spin labeling of proteins has enabled EPR studies to expand into newer research areas within the umbrella of protein-membrane interactions. Recently, membrane remodeling by amyloidogenic and non-amyloidogenic proteins has gained a substantial interest in relation to driving and controlling vital cellular processes such as endocytosis, exocytosis, shaping of organelles like endoplasmic reticulum, Golgi and mitochondria, intracellular vesicular trafficking, formation of filopedia and multivesicular bodies, mitochondrial fusion and fission, and synaptic vesicle fusion and recycling in neurotransmission. Misregulation in any of these processes due to an aberrant protein (mutation or misfolding) or alteration of lipid metabolism can be detrimental to the cell and cause disease. Dissection of the structural basis of membrane remodeling by proteins is thus quite necessary for an understanding of the underlying mechanisms, but it remains a formidable task due to the difficulties of various common biophysical tools in monitoring the dynamic process of membrane binding and bending by proteins. This is largely since membranes generally complicate protein structure analysis and this problem is amplified for structural analysis in the presence of different types of membrane curvatures. Recent EPR studies on membrane remodeling by proteins show that a significant structural information can be generated to delineate the role of different protein modules, domains and individual amino acids in the generation of membrane curvature. These studies also show how EPR can complement the data obtained by high resolution techniques such as X-ray and NMR. This perspective covers the application of EPR in recent studies for understanding membrane remodeling by amyloidogenic and non-amyloidogenic proteins that is useful for researchers interested in using or complimenting EPR to gain better understanding of membrane remodeling. We also discuss how a single protein can generate different type of membrane curvatures using specific conformations for specific membrane structures and how EPR is a versatile tool well-suited to analyze subtle alterations in structures under such modifying conditions which otherwise would have been difficult using other biophysical tools.

Multiple roles of the Rho GEF ephexin1 in synapse remodeling

PubMed Central

Shi, Lei; Fu, Amy KY

2010-01-01

Synapse remodeling, which involves changes in the synaptic structure and their molecular composition, is required for the maturation and refinement of neural circuits. Although synapse remodeling is known to be tightly dependent on the assembly of local actin cytoskeleton, how actin directs the structural changes of synapse and targeting of synaptic proteins are not fully understood. Recently, we identified ephexin1, a Rho guanine nucleotide exchange factor (GEF) that regulates actin dynamics, to play an essential role in the maturation and functioning of the mammalian neuromuscular junction (NMJ). We showed that ephexin1 regulates the synaptic organization of the neurotransmitter receptor acetylcholine receptor (AChR) clusters through RhoA-dependent actin reorganization. Interestingly, ephexin1 has been implicated in the regulation of postsynaptic structure as well as the presynaptic vesicle release at various types of synapses. Our findings thus establish a novel function of ephexin1 in synapse remodeling through regulating the synaptic targeting of neurotransmitter receptors, revealing a versatile role of ephexin1 at synapses. PMID:21331259

Regulation of the basement membrane by epithelia generated forces

NASA Astrophysics Data System (ADS)

Tanner, Kandice

2012-12-01

Tumor metastasis involves a progressive loss of tissue architecture and dissolution of structural boundaries between the epithelium and connective tissue. The basement membrane (BM), a specialized network of extracellular matrix proteins forms a barrier that physically restricts pre-invasive lesions such that they remain as local insults. The BM is not a static structure, but one that is constantly regenerated and remodeled in the adult organism. Matrix organization also regulates cell function. Thus alterations in the balance of synthesis, remodeling and proteolytic degradation of the extracellular matrix proteins may contribute to a loss of structural integrity. However, the de novo assembly and maintenance of the complex structural properties of in vivo basement membranes remain elusive. Here, this paper highlights the current understanding on the structural properties and the establishment of the BM, and discusses the potential role of self-generated forces in adult tissue remodeling and the maintenance of the BM as a malignancy suppressor.

Recent developments in metabolic bone diseases: a gnathic perspective.

PubMed

Raubenheimer, Erich J; Noffke, Claudia E; Hendrik, Hilde D

2014-12-01

Metabolic bone diseases often are asymptomatic and progress sub clinically. Many patients present at a late stage with catastrophic skeletal and extra skeletal complications. In this article, we provide an overview of normal bone remodeling and a synopsis of recent developments in the following conditions: osteoporosis, rickets/osteomalacia, endocrine-induced bone disease, chronic kidney disease-mineral bone disorder and Paget's disease of bone. Our discussion will emphasize the clinical and microscopic manifestations of these diseases in the jaws.

Character of skin on photo-thermal response and its regeneration process using second-harmonic generation microscopy.

PubMed

Wu, Shu-lian; Li, Hui; Zhang, Xiao-man; Chen, Wei R; Wang, Yun-Xia

2014-01-01

Quantitative characterization of skin collagen on photo-thermal response and its regeneration process is an important but difficult task. In this study, morphology and spectrum characteristics of collagen during photo-thermal response and its light-induced remodeling process were obtained by second-harmonic generation microscope in vivo. The texture feature of collagen orientation index and fractal dimension was extracted by image processing. The aim of this study is to detect the information hidden in skin texture during the process of photo-thermal response and its regeneration. The quantitative relations between injured collagen and texture feature were established for further analysis of the injured characteristics. Our results show that it is feasible to determine the main impacts of phototherapy on the skin. It is important to understand the process of collagen remodeling after photo-thermal injuries from texture feature.

Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis.

PubMed

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

2017-11-01

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.

Mandibular bone remodeling under a choline-deficient diet: a histomorphometric study in rats.

PubMed

Gorustovich, Alejandro A; Espósito, María A; Guglielmotti, María B; Giglio, Máximo J

2003-06-01

A deficiency of lipotropic factors in the rat induces renal, hepatic, and/or hematic damage. The aim of the present study was to evaluate the effect of a choline-deficient diet and refeeding on mandibular bone remodeling. Fifty Wistar rats were divided into 5 groups: group 1 (G1): control diet for 15 days; group 2 (G2): choline-deficient diet for 15 days; group 3 (G3): control diet for 30 days; group 4 (G4): choline-deficient diet for 30 days; and group 5 (G5): choline-deficient diet for 15 days and control diet for 15 days. All animals were sacrificed by ether overdose. The mandibles were resected, radiographed, decalcified, processed, and embedded in paraffin. Bucco-lingually oriented sections were obtained at the level of the interradicular bone of the medial roots of the left first molar, and stained with hematoxylin and eosin (H & E). Bone tissue density and bone remodeling were determined histomorphometrically. Body weight, food intake, hematocrit, and hemoglobinemia were also recorded. Microscopic observation revealed that osteogenesis was lower in rats fed a choline-deficient diet, at both 15 and 30 days, and that this decrease did not revert with a control diet. Histomorphometric evaluation showed 37% and 27% reduction in bone tissue density at 15 and 30 days, respectively, and a 30% decrease in bone formation at 30 days, compared to controls. In this experimental model, a choline-deficient diet led to altered bone remodeling as observed by a marked reduction in osteogenesis.

Dynamic expression of chymotrypsin-like elastase 1 over the course of murine lung development

PubMed Central

Liu, Sheng; Young, Sarah Marie

2014-01-01

Postnatal lung development requires coordination of three processes (surface area expansion, microvascular growth, and matrix remodeling). Because normal elastin structure is important for lung morphogenesis, because physiological remodeling of lung elastin has never been defined, and because elastin remodeling is angiogenic, we sought to test the hypothesis that, during lung development, elastin is remodeled in a defined temporal-spatial pattern, that a novel protease is associated with this remodeling, and that angiogenesis is associated with elastin remodeling. By elastin in situ zymography, lung elastin remodeling increased 24-fold between embryonic day (E) 15.5 and postnatal day (PND) 14. Remodeling was restricted to major vessels and airways on PND1 with a sevenfold increase in alveolar wall elastin remodeling from PND1 to PND14. By inhibition assays and literature review, we identified chymotrypsin-like elastase 1 (CELA1) as a potential mediator of elastin remodeling. CELA1 mRNA levels increased 12-fold from E15.5 to PND9, and protein levels increased 3.4-fold from E18.5 to PND9. By costaining experiments, the temporal-spatial pattern of CELA1 expression matched that of elastin remodeling, and 58–85% of CELA1+ cells were <10 μm from an elastase signal. An association between elastin remodeling and angiogenesis was tested by similar methods. At PND7 and PND14, 60–95% of angiogenin+ cells were associated with elastin remodeling. Both elastase inhibition and CELA1 silencing impaired angiogenesis in vitro. Our data defines the temporal-spatial pattern of elastin remodeling during lung development, demonstrates an association of this remodeling with CELA1, and supports a role for elastin remodeling in regulating angiogenesis. PMID:24793170

Activity-Induced Synaptic Structural Modifications by an Activator of Integrin Signaling at the Drosophila Neuromuscular Junction.

PubMed

Lee, Joo Yeun; Geng, Junhua; Lee, Juhyun; Wang, Andrew R; Chang, Karen T

2017-03-22

Activity-induced synaptic structural modification is crucial for neural development and synaptic plasticity, but the molecular players involved in this process are not well defined. Here, we report that a protein named Shriveled (Shv) regulates synaptic growth and activity-dependent synaptic remodeling at the Drosophila neuromuscular junction. Depletion of Shv causes synaptic overgrowth and an accumulation of immature boutons. We find that Shv physically and genetically interacts with βPS integrin. Furthermore, Shv is secreted during intense, but not mild, neuronal activity to acutely activate integrin signaling, induce synaptic bouton enlargement, and increase postsynaptic glutamate receptor abundance. Consequently, loss of Shv prevents activity-induced synapse maturation and abolishes post-tetanic potentiation, a form of synaptic plasticity. Our data identify Shv as a novel trans-synaptic signal secreted upon intense neuronal activity to promote synapse remodeling through integrin receptor signaling. SIGNIFICANCE STATEMENT The ability of neurons to rapidly modify synaptic structure in response to neuronal activity, a process called activity-induced structural remodeling, is crucial for neuronal development and complex brain functions. The molecular players that are important for this fundamental biological process are not well understood. Here we show that the Shriveled (Shv) protein is required during development to maintain normal synaptic growth. We further demonstrate that Shv is selectively released during intense neuronal activity, but not mild neuronal activity, to acutely activate integrin signaling and trigger structural modifications at the Drosophila neuromuscular junction. This work identifies Shv as a key modulator of activity-induced structural remodeling and suggests that neurons use distinct molecular cues to differentially modulate synaptic growth and remodeling to meet synaptic demand. Copyright © 2017 the authors 0270-6474/17/373246-18$15.00/0.

From changes in local RAAS to structural remodeling of the left atrium: A beautiful cycle in atrial fibrillation.

PubMed

Yongjun, Q; Huanzhang, S; Wenxia, Z; Hong, T; Xijun, X

2015-05-01

In earlier studies, we reported structural remodeling was associated with atrial fibrillation (AF) and showed that the renin-angiotensin-aldosterone system (RAAS) was linked to AF. It is reasonable to hypothesize that there is a cycle, from RAAS to structural remodeling to AF. Our study group consisted of 80 patients scheduled for mitral valve replacement surgery. Tissue samples of the left atrial appendages were obtained. Masson's trichrome staining and immunohistochemical staining were performed to assess the extent of fibrosis. Radioimmunoassay was carried out to investigate the expression levels of local RAAS. RAAS-related genes were analyzed by RT-PCR. There was a significantly increased degree of fibrosis in AF patients compared with sinus rhythm (SR) patients (p = 0.023). There were significant differences in the expression levels of local angiotensin (Ang) II between the SR and the AF groups (p = 0.002). The expression levels of local Ang II correlated with the duration of AF (r = 0.727851, p = 0.001) and with collagen type I (r = 0.672189, p = 0.032). In the AF group, the mRNA expressions of the AT1R and ACE genes were markedly up-regulated in comparison with the SR group (p = 0.021 and p = 0.037). On the basis of this study, and in combination with results of our previous studies, we demonstrate for the first time that there is a cycle involving RAAS, structural remodeling, and AF. RAAS, structural remodeling, and AF are the principal aspects in this cycle.

Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression.

PubMed

Hajszan, Tibor; Dow, Antonia; Warner-Schmidt, Jennifer L; Szigeti-Buck, Klara; Sallam, Nermin L; Parducz, Arpad; Leranth, Csaba; Duman, Ronald S

2009-03-01

Although it has been postulated for many years that depression is associated with loss of synapses, primarily in the hippocampus, and that antidepressants facilitate synapse growth, we still lack ultrastructural evidence that changes in depressive behavior are indeed correlated with structural synaptic modifications. We analyzed hippocampal spine synapses of male rats (n=127) with electron microscopic stereology in association with performance in the learned helplessness paradigm. Inescapable footshock (IES) caused an acute and persistent loss of spine synapses in each of CA1, CA3, and dentate gyrus, which was associated with a severe escape deficit in learned helplessness. On the other hand, IES elicited no significant synaptic alterations in motor cortex. A single injection of corticosterone reproduced both the hippocampal synaptic changes and the behavioral responses induced by IES. Treatment of IES-exposed animals for 6 days with desipramine reversed both the hippocampal spine synapse loss and the escape deficit in learned helplessness. We noted, however, that desipramine failed to restore the number of CA1 spine synapses to nonstressed levels, which was associated with a minor escape deficit compared with nonstressed control rats. Shorter, 1-day or 3-day desipramine treatments, however, had neither synaptic nor behavioral effects. These results indicate that changes in depressive behavior are associated with remarkable remodeling of hippocampal spine synapses at the ultrastructural level. Because spine synapse loss contributes to hippocampal dysfunction, this cellular mechanism may be an important component in the neurobiology of stress-related disorders such as depression.

Fibrous tissues growth and remodeling: Evolutionary micro-mechanical theory

NASA Astrophysics Data System (ADS)

Lanir, Yoram

2017-10-01

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.

Modalities for Visualization of Cortical Bone Remodeling: The Past, Present, and Future

PubMed Central

Harrison, Kimberly D.; Cooper, David M. L.

2015-01-01

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 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 of 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 architecture.” 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.” PMID:26322017

Structural and molecular remodeling of dendritic spine substructures during long-term potentiation

PubMed Central

Bosch, Miquel; Castro, Jorge; Saneyoshi, Takeo; Matsuno, Hitomi; Sur, Mriganka; Hayashi, Yasunori

2014-01-01

SUMMARY Synapses store information by long-lasting modifications of their structure and molecular composition, but the precise chronology of these changes has not been studied at single synapse resolution in real time. Here we describe the spatiotemporal reorganization of postsynaptic substructures during long-term potentiation (LTP) at individual dendritic spines. Proteins translocated to the spine in four distinct patterns through three sequential phases. In the initial phase, the actin cytoskeleton was rapidly remodeled while active cofilin was massively transported to the spine. In the stabilization phase, cofilin formed a stable complex with F-actin, was persistently retained at the spine, and consolidated spine expansion. In contrast, the postsynaptic density (PSD) was independently remodeled, as PSD scaffolding proteins did not change their amount and localization until a late protein synthesis-dependent third phase. Our findings show how and when spine substructures are remodeled during LTP and explain why synaptic plasticity rules change over time. PMID:24742465

Scleraxis is required for cell lineage differentiation and extracellular matrix remodeling during murine heart valve formation in vivo.

PubMed

Levay, Agata K; Peacock, Jacqueline D; Lu, Yinhui; Koch, Manuel; Hinton, Robert B; Kadler, Karl E; Lincoln, Joy

2008-10-24

Heart valve structures, derived from mesenchyme precursor cells, are composed of differentiated cell types and extracellular matrix arranged to facilitate valve function. Scleraxis (scx) is a transcription factor required for tendon cell differentiation and matrix organization. This study identified high levels of scx expression in remodeling heart valve structures at embryonic day 15.5 through postnatal stages using scx-GFP reporter mice and determined the in vivo function using mice null for scx. Scx(-/-) mice display significantly thickened heart valve structures from embryonic day 17.5, and valves from mutant mice show alterations in valve precursor cell differentiation and matrix organization. This is indicated by decreased expression of the tendon-related collagen type XIV, increased expression of cartilage-associated genes including sox9, as well as persistent expression of mesenchyme cell markers including msx1 and snai1. In addition, ultrastructure analysis reveals disarray of extracellular matrix and collagen fiber organization within the valve leaflet. Thickened valve structures and increased expression of matrix remodeling genes characteristic of human heart valve disease are observed in juvenile scx(-/-) mice. In addition, excessive collagen deposition in annular structures within the atrioventricular junction is observed. Collectively, our studies have identified an in vivo requirement for scx during valvulogenesis and demonstrate its role in cell lineage differentiation and matrix distribution in remodeling valve structures.

The Chd1 Chromatin Remodeler Shifts Nucleosomal DNA Bidirectionally as a Monomer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Yupeng; Levendosky, Robert F.; Chakravarthy, Srinivas

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 withmore » 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.« less

Mmp1 processing of the PDF neuropeptide regulates circadian structural plasticity of pacemaker neurons.

PubMed

Depetris-Chauvin, Ana; Fernández-Gamba, Agata; Gorostiza, E Axel; Herrero, Anastasia; Castaño, Eduardo M; Ceriani, M Fernanda

2014-10-01

In the Drosophila brain, the neuropeptide PIGMENT DISPERSING FACTOR (PDF) is expressed in the small and large Lateral ventral neurons (LNvs) and regulates circadian locomotor behavior. Interestingly, PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result of a remarkable remodeling of sLNv projections. Despite the relevance of this phenomenon to circuit plasticity and behavior, the underlying mechanisms remain poorly understood. In this work we provide evidence that PDF along with matrix metalloproteinases (Mmp1 and 2) are key in the control of circadian structural remodeling. Adult-specific downregulation of PDF levels per se hampers circadian axonal remodeling, as it does altering Mmp1 or Mmp2 levels within PDF neurons post-developmentally. However, only Mmp1 affects PDF immunoreactivity at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by Mmp1, thereby suggesting that Mmp1 could directly terminate its biological activity. These data demonstrate that Mmp1 modulates PDF processing, which leads to daily structural remodeling and circadian behavior.

Mmp1 Processing of the PDF Neuropeptide Regulates Circadian Structural Plasticity of Pacemaker Neurons

PubMed Central

Depetris-Chauvin, Ana; Fernández-Gamba, Ágata; Gorostiza, E. Axel; Herrero, Anastasia; Castaño, Eduardo M.; Ceriani, M. Fernanda

2014-01-01

In the Drosophila brain, the neuropeptide PIGMENT DISPERSING FACTOR (PDF) is expressed in the small and large Lateral ventral neurons (LNvs) and regulates circadian locomotor behavior. Interestingly, PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result of a remarkable remodeling of sLNv projections. Despite the relevance of this phenomenon to circuit plasticity and behavior, the underlying mechanisms remain poorly understood. In this work we provide evidence that PDF along with matrix metalloproteinases (Mmp1 and 2) are key in the control of circadian structural remodeling. Adult-specific downregulation of PDF levels per se hampers circadian axonal remodeling, as it does altering Mmp1 or Mmp2 levels within PDF neurons post-developmentally. However, only Mmp1 affects PDF immunoreactivity at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by Mmp1, thereby suggesting that Mmp1 could directly terminate its biological activity. These data demonstrate that Mmp1 modulates PDF processing, which leads to daily structural remodeling and circadian behavior. PMID:25356918

Lung capillary injury and repair in left heart disease: a new target for therapy?

PubMed

Azarbar, Sayena; Dupuis, Jocelyn

2014-07-01

The lungs are the primary organs affected in LHD (left heart disease). Increased left atrial pressure leads to pulmonary alveolar-capillary stress failure, resulting in cycles of alveolar wall injury and repair. The reparative process causes the proliferation of MYFs (myofibroblasts) with fibrosis and extracellular matrix deposition, resulting in thickening of the alveolar wall. Although the resultant reduction in vascular permeability is initially protective against pulmonary oedema, the process becomes maladaptive causing a restrictive lung syndrome with impaired gas exchange. This pathological process may also contribute to PH (pulmonary hypertension) due to LHD. Few clinical trials have specifically evaluated lung structural remodelling and the effect of related therapies in LHD. Currently approved treatment for chronic HF (heart failure) may have direct beneficial effects on lung structural remodelling. In the future, novel therapies specifically targeting the remodelling processes may potentially be utilized. In the present review, we summarize data supporting the clinical importance and pathophysiological mechanisms of lung structural remodelling in LHD and propose that this pathophysiological process should be explored further in pre-clinical studies and future therapeutic trials.

Imaging denatured collagen strands in vivo and ex vivo via photo-triggered hybridization of caged collagen mimetic peptides.

PubMed

Li, Yang; Foss, Catherine A; Pomper, Martin G; Yu, S Michael

2014-01-31

Collagen is a major structural component of the extracellular matrix that supports tissue formation and maintenance. Although collagen remodeling is an integral part of normal tissue renewal, excessive amount of remodeling activity is involved in tumors, arthritis, and many other pathological conditions. During collagen remodeling, the triple helical structure of collagen molecules is disrupted by proteases in the extracellular environment. In addition, collagens present in many histological tissue samples are partially denatured by the fixation and preservation processes. Therefore, these denatured collagen strands can serve as effective targets for biological imaging. We previously developed a caged collagen mimetic peptide (CMP) that can be photo-triggered to hybridize with denatured collagen strands by forming triple helical structure, which is unique to collagens. The overall goals of this procedure are i) to image denatured collagen strands resulting from normal remodeling activities in vivo, and ii) to visualize collagens in ex vivo tissue sections using the photo-triggered caged CMPs. To achieve effective hybridization and successful in vivo and ex vivo imaging, fluorescently labeled caged CMPs are either photo-activated immediately before intravenous injection, or are directly activated on tissue sections. Normal skeletal collagen remolding in nude mice and collagens in prefixed mouse cornea tissue sections are imaged in this procedure. The imaging method based on the CMP-collagen hybridization technology presented here could lead to deeper understanding of the tissue remodeling process, as well as allow development of new diagnostics for diseases associated with high collagen remodeling activity.

The angiotensin receptor blocker losartan reduces coronary arteriole remodeling in type 2 diabetic mice

PubMed Central

Husarek, Kathryn E.; Katz, Paige S.; Trask, Aaron J.; Galantowicz, Maarten L.; Cismowski, Mary J.; Lucchesi, Pamela A.

2017-01-01

Cardiovascular complications are a leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM) and are associated with alterations of blood vessel structure and function. Although endothelial dysfunction and aortic stiffness have been documented, little is known about the effects of T2DM on coronary microvascular structural remodeling. The renin–angiotensin–aldosterone system plays an important role in large artery stiffness and mesenteric vessel remodeling in hypertension and T2DM. The goal of this study was to determine whether the blockade of AT1R signaling dictates vascular smooth muscle growth that partially underlies coronary arteriole remodeling in T2DM. Control and db/db mice were given AT1R blocker losartan via drinking water for 4 weeks. Using pressure myography, we found that coronary arterioles from 16-week db/db mice undergo inward hypertrophic remodeling due to increased wall thickness and wall-to-lumen ratio with a decreased lumen diameter. This remodeling was accompanied by decreased elastic modulus (decreased stiffness). Losartan treatment decreased wall thickness, wall-to-lumen ratio, and coronary arteriole cell number in db/db mice. Losartan treatment did not affect incremental elastic modulus. However, losartan improved coronary flow reserve. Our data suggest that Ang II–AT1R signaling mediates, at least in part, coronary arteriole inward hypertrophic remodeling in T2DM without affecting vascular mechanics, further suggesting that targeting the coronary microvasculature in T2DM may help reduce cardiac ischemic events. PMID:26133668

Membrane remodeling by amyloidogenic and non-amyloidogenic proteins studied by EPR.

PubMed

Varkey, Jobin; Langen, Ralf

2017-07-01

The advancement in site-directed spin labeling of proteins has enabled EPR studies to expand into newer research areas within the umbrella of protein-membrane interactions. Recently, membrane remodeling by amyloidogenic and non-amyloidogenic proteins has gained a substantial interest in relation to driving and controlling vital cellular processes such as endocytosis, exocytosis, shaping of organelles like endoplasmic reticulum, Golgi and mitochondria, intracellular vesicular trafficking, formation of filopedia and multivesicular bodies, mitochondrial fusion and fission, and synaptic vesicle fusion and recycling in neurotransmission. Misregulation in any of these processes due to an aberrant protein (mutation or misfolding) or alteration of lipid metabolism can be detrimental to the cell and cause disease. Dissection of the structural basis of membrane remodeling by proteins is thus quite necessary for an understanding of the underlying mechanisms, but it remains a formidable task due to the difficulties of various common biophysical tools in monitoring the dynamic process of membrane binding and bending by proteins. This is largely since membranes generally complicate protein structure analysis and this problem is amplified for structural analysis in the presence of different types of membrane curvatures. Recent EPR studies on membrane remodeling by proteins show that a significant structural information can be generated to delineate the role of different protein modules, domains and individual amino acids in the generation of membrane curvature. These studies also show how EPR can complement the data obtained by high resolution techniques such as X-ray and NMR. This perspective covers the application of EPR in recent studies for understanding membrane remodeling by amyloidogenic and non-amyloidogenic proteins that is useful for researchers interested in using or complimenting EPR to gain better understanding of membrane remodeling. We also discuss how a single protein can generate different type of membrane curvatures using specific conformations for specific membrane structures and how EPR is a versatile tool well-suited to analyze subtle alterations in structures under such modifying conditions which otherwise would have been difficult using other biophysical tools. Copyright © 2017 Elsevier Inc. All rights reserved.

High-resolution study of the 3D collagen fibrillary matrix of Achilles tendons without tissue labelling and dehydrating.

PubMed

Wu, Jian-Ping; Swift, Benjamin John; Becker, Thomas; Squelch, Andrew; Wang, Allan; Zheng, Yong-Chang; Zhao, Xuelin; Xu, Jiake; Xue, Wei; Zheng, Minghao; Lloyd, David; Kirk, Thomas Brett

2017-06-01

Knowledge of the collagen structure of an Achilles tendon is critical to comprehend the physiology, biomechanics, homeostasis and remodelling of the tissue. Despite intensive studies, there are still uncertainties regarding the microstructure. The majority of studies have examined the longitudinally arranged collagen fibrils as they are primarily attributed to the principal tensile strength of the tendon. Few studies have considered the structural integrity of the entire three-dimensional (3D) collagen meshwork, and how the longitudinal collagen fibrils are integrated as a strong unit in a 3D domain to provide the tendons with the essential tensile properties. Using second harmonic generation imaging, a 3D imaging technique was developed and used to study the 3D collagen matrix in the midportion of Achilles tendons without tissue labelling and dehydration. Therefore, the 3D collagen structure is presented in a condition closely representative of the in vivo status. Atomic force microscopy studies have confirmed that second harmonic generation reveals the internal collagen matrix of tendons in 3D at a fibril level. Achilles tendons primarily contain longitudinal collagen fibrils that braid spatially into a dense rope-like collagen meshwork and are encapsulated or wound tightly by the oblique collagen fibrils emanating from the epitenon region. The arrangement of the collagen fibrils provides the longitudinal fibrils with essential structural integrity and endows the tendon with the unique mechanical function for withstanding tensile stresses. A novel 3D microscopic method has been developed to examine the 3D collagen microstructure of tendons without tissue dehydrating and labelling. The study also provides new knowledge about the collagen microstructure in an Achilles tendon, which enables understanding of the function of the tissue. The knowledge may be important for applying surgical and tissue engineering techniques to tendon reconstruction. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Physiological Implications of Myocardial Scar Structure

PubMed Central

Richardson, WJ; Clarke, SA; Quinn, TA; Holmes, JW

2016-01-01

Once myocardium dies during a heart attack, it is replaced by scar tissue over the course of several weeks. The size, location, composition, structure and mechanical properties of the healing scar are all critical determinants of the fate of patients who survive the initial infarction. While the central importance of scar structure in determining pump function and remodeling has long been recognized, it has proven remarkably difficult to design therapies that improve heart function or limit remodeling by modifying scar structure. Many exciting new therapies are under development, but predicting their long-term effects requires a detailed understanding of how infarct scar forms, how its properties impact left ventricular function and remodeling, and how changes in scar structure and properties feed back to affect not only heart mechanics but also electrical conduction, reflex hemodynamic compensations, and the ongoing process of scar formation itself. In this article, we outline the scar formation process following an MI, discuss interpretation of standard measures of heart function in the setting of a healing infarct, then present implications of infarct scar geometry and structure for both mechanical and electrical function of the heart and summarize experiences to date with therapeutic interventions that aim to modify scar geometry and structure. One important conclusion that emerges from the studies reviewed here is that computational modeling is an essential tool for integrating the wealth of information required to understand this complex system and predict the impact of novel therapies on scar healing, heart function, and remodeling following myocardial infarction. PMID:26426470

Effects of nucleosome stability on remodeler-catalyzed repositioning

NASA Astrophysics Data System (ADS)

Morgan, Aaron M.; LeGresley, Sarah E.; Briggs, Koan; Al-Ani, Gada; Fischer, Christopher J.

2018-03-01

Chromatin remodelers are molecular motors that play essential roles in the regulation of nucleosome positioning and chromatin accessibility. These machines couple the energy obtained from the binding and hydrolysis of ATP to the mechanical work of manipulating chromatin structure through processes that are not completely understood. Here we present a quantitative analysis of nucleosome repositioning by the imitation switch (ISWI) chromatin remodeler and demonstrate that nucleosome stability significantly impacts the observed activity. We show how DNA damage induced changes in the affinity of DNA wrapping within the nucleosome can affect ISWI repositioning activity and demonstrate how assay-dependent limitations can bias studies of nucleosome repositioning. Together, these results also suggest that some of the diversity seen in chromatin remodeler activity can be attributed to the variations in the thermodynamics of interactions between the remodeler, the histones, and the DNA, rather than reflect inherent properties of the remodeler itself.

Nanointaglio fabrication of optical lipid multilayer diffraction gratings with applications in biosensing

NASA Astrophysics Data System (ADS)

Lowry, Troy Warren

The dynamic self-organization of lipids in biological systems is a highly regulated process that enables the compartmentalization of living systems at microscopic and nanoscopic levels. Exploiting the self-organization and innate biofunctionality of lyotropic liquid crystalline phospholipids, a novel nanofabrication process called "nanointaglio" was invented in order to rapidly and scalably integrate lipid nanopatterns onto the surface. The work presented here focuses on using nanointaglio fabricated lipid diffraction micro- and nanopatterns for the development of new sensing and bioactivity studies. The lipids are patterned as diffraction gratings for sensor functionality. The lipid multilayer gratings operate as nanomechanical sensor elements that are capable of transducing molecular binding to fluid lipid multilayers into optical signals in a label free manner due to shape changes in the lipid nanostructures. To demonstrate the label free detection capabilities, lipid nanopatterns are shown to be suitable for the integration of chemically different lipid multilayer gratings into a sensor array capable of distinguishing vapors by means of an optical nose. Sensor arrays composed of six different lipid formulations are integrated onto a surface and their optical response to three different vapors (water, ethanol and acetone) in air as well as pH under water is monitored as a function of time. Principal component analysis of the array response results in distinct clustering, indicating the suitability of the arrays for distinguishing these analytes. Importantly, the nanointaglio process used is capable of producing lipid gratings out of different materials with sufficiently uniform heights for the fabrication of an optical nose. A second main application is demonstrated for the study of membrane binding proteins. Although in vitro methods for assaying the catalytic activity of individual enzymes are well established, quantitative methods for assaying the kinetics of supramolecular remodeling such as vesicle formation from planar lipid bilayers or multilayers are needed to understand cellular self-organization. Presented next is a nanointaglio based method for quantitative measurements of lipid-protein interactions and its suitability for quantifying the membrane binding, inflation, and budding activity of the membrane-remodeling protein Sar1. Optical diffraction gratings composed of lipids are printed on surfaces using nanointaglio, resulting in lipid multilayer gratings. Exposure of lipid multilayer gratings to Sar1 results in the inflation of lipid multilayers into unilamellar structures, the kinetics of which can be detected in a label-free manner by monitoring the diffraction of white light through an optical microscope. Local variations in lipid multilayer volume on the surface can be used to vary substrate availability in a microarray format, allowing kinetic and thermodynamic data to be obtained from a single experiment without the need for varying enzyme concentration. A quantitative model is developed and fits to the data allow measurements of both binding affinity (KD) and kinetics (kon and koff). Importantly, this assay is uniquely capable of quantifying membrane remodeling. Upon Sar1 induced inflation of single bilayers from surface supported multilayers, the semi-cylindrical grating lines are observed to remodel into semi-spherical buds when a critical radius of curvature equal to 300 nm is reached, which is explained in terms of a Rayleigh type instability.

Understanding the structural features of symptomatic calcific aortic valve stenosis: A broad-spectrum clinico-pathologic study in 236 consecutive surgical cases.

PubMed

Galli, Daniela; Manuguerra, Roberta; Monaco, Rodolfo; Manotti, Laura; Goldoni, Matteo; Becchi, Gabriella; Carubbi, Cecilia; Vignali, Giulia; Cucurachi, Nicola; Gherli, Tiziano; Nicolini, Francesco; Lorusso, Roberto; Vitale, Marco; Corradi, Domenico

2017-02-01

With age, aortic valve cusps undergo varying degrees of sclerosis which, sometimes, can progress to calcific aortic valve stenosis (AVS). To perform a retrospective clinico-pathologic investigation in patients with calcific AVS. We characterized and graded the structural remodeling in 236 aortic valves (200 tricuspid and 36 bicuspid) from patients with calcific AVS (148 males; average 72years); possible relationships between general/clinical/echocardiographic characteristics and the histopathologic changes were explored. Twenty autopsy aortic valves served as controls. In 40 cases, we also tested the immunohistochemical expression of metalloproteinases and cytokines, and characterized the inflammatory infiltrate. In 5 cases, we cultured cusp stem cells and explored their potential to differentiate into osteoblasts/adipocytes. AVS cusps showed structural remodeling as severe fibrosis (100%), calcific nodules (100%), neoangiogenesis (81%), inflammation (71%), bone metaplasia with or without hematopoiesis (6% and 53%, respectively), adipose metaplasia (16%), and cartilaginous metaplasia (7%). At multivariate analysis, AVS degree and interventricular septum thickness were the only predictors of remodeling (barring inflammation). All the tested metalloproteinases (except MMP-13) and cytokines were expressed in AVS cusps. Inflammation mainly consisted of B and T lymphocytes (CD4+/CD8+ cell ratio 3:1) and plasma cells. AVS changes were mostly different from typical atherosclerosis. Cultured mesenchymal cusp stem cells could differentiate into osteoblasts/adipocytes. Structural remodeling in AVS is peculiar and considerable, and is related to the severity of the disease. However, the different newly formed tissues-where "valvular interstitial cells" play a key role-and their well-known slow turnover suggest a reverse structural remodeling improbable. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells

NASA Astrophysics Data System (ADS)

Xu, Wenwei; Mezencev, Roman; Kim, Byungkyu; Wang, Lijuan; McDonald, John; Sulchek, Todd; Sulchek Team; McDonald Team

2013-03-01

The metastatic potential of cells is an important parameter in the design of optimal strategies for the personalized treatment of cancer. Using atomic force microscopy (AFM), we show that ovarian cancer cells are generally softer and display lower intrinsic variability in cell stiffness than non-malignant ovarian epithelial cells. A detailed study of highly invasive ovarian cancer cells (HEY A8) and their less invasive parental cells (HEY), demonstrates that deformability can serve as an accurate biomarker of metastatic potential. Comparative gene expression profiling indicate that the reduced stiffness of highly metastatic HEY A8 cells is associated with actin cytoskeleton remodeling, microscopic examination of actin fiber structure in these cell lines is consistent with this prediction. Our results indicate that cell stiffness not only distinguishes ovarian cancer cells from non-malignant cells, but may also be a useful biomarker to evaluate the relative metastatic potential of ovarian and perhaps other types of cancer cells.

Simulations of Biomechanical Phenomena

NASA Astrophysics Data System (ADS)

Gonzalez, Jose Cruz

Recent studies have published breakthroughs in the application of finite element (FEA) studies in the design and analysis of advanced orthodontics. However, FEA has not captured bone remodeling responses to advanced orthodontics. The results of these simulations report unrealistic displacement around the nasal bridge, which impeded correlation with clinical data. Bone remodeling has been previously documented in FEA and has shown bone response to mechanical stimulus in femur bone models. However, the relationship between mechanical stimulus and bone remodeling has not been reported in orthodontic studies due to the complexity of the skull. In the current study, strain energy is used as the mechanical stimulus to control remodeling, from which density and modulus evolve. Due to the localization of forces in orthodontics, current remodeling algorithms have limited application. In turn, we developed an algorithm that dynamically collects, sorts, and bins stresses in all elements for regional remodeling based on the proximity of the element to the load. The results demonstrate that bone response to orthodontic appliances is different than that of an FEA without bone remodeling, due to load path changes based upon evolution of the bone properties. It was also found that density and moduli proximal to the load application site exhibit faster remodeling than those located remotely. Modeling another biomechanical phenomena, a 3D simulation was created to simulate recent experimental results that discovered a difference in impact mitigation properties of dense-polymer/foam bilayer structure based on the orientation of the dense-polymer with respect to the impact site. The impact energy transmitted varied in time of arrival and amplitude depending on the orientation of the structure (thin layer up or down). By creating a 3D explicit dynamic FEA simulation, it is expected to reduce costly experiments and time consumed in set up, and offer opportunities for optimization for future applications in armor. The results agreed with the experimental results, displaying a delay in impact wave arrival, depending on the orientation of the structure. The FEA revealed also revealed that mid-body strains showed an increase at different time intervals, indicating the dense polymer's engagement and impact mitigation.

Correlation of structural stability with functional remodeling of high-density lipoproteins: the importance of being disordered.

PubMed

Guha, Madhumita; Gao, Xuan; Jayaraman, Shobini; Gursky, Olga

2008-11-04

High-density lipoproteins (HDLs) are protein-lipid assemblies that remove excess cell cholesterol and prevent atherosclerosis. HDLs are stabilized by kinetic barriers that decelerate protein dissociation and lipoprotein fusion. We propose that similar barriers modulate metabolic remodeling of plasma HDLs; hence, changes in particle composition that destabilize HDLs and accelerate their denaturation may accelerate their metabolic remodeling. To test this notion, we correlate existing reports on HDL-mediated cell cholesterol efflux and esterification, which are obligatory early steps in cholesterol removal, with our kinetic studies of HDL stability. The results support our hypothesis and show that factors accelerating cholesterol efflux and esterification in model discoidal lipoproteins (including reduced protein size, reduced fatty acyl chain length, and/or increased level of cis unsaturation) destabilize lipoproteins and accelerate their fusion and apolipoprotein dissociation. Oxidation studies of plasma spherical HDLs show a similar trend: mild oxidation by Cu(2+) or OCl(-) accelerates cell cholesterol efflux, protein dissociation, and HDL fusion, while extensive oxidation inhibits these reactions. Consequently, moderate destabilization may be beneficial for HDL functions by facilitating insertion of cholesterol and lipophilic enzymes, promoting dissociation of lipid-poor apolipoproteins, which are primary acceptors of cell cholesterol, and thereby accelerating HDL metabolism. Therefore, HDL stability must be delicately balanced to maintain the structural integrity of the lipoprotein assembly and ensure structural specificity necessary for interactions of HDL with its metabolic partners, while facilitating rapid HDL remodeling and turnover at key junctures of cholesterol transport. The inverse correlation between HDL stability and remodeling illustrates the functional importance of structural disorder in macromolecular assemblies stabilized by kinetic barriers.

Aging by epigenetics-A consequence of chromatin damage?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sedivy, John M.; Banumathy, Gowrishankar; Adams, Peter D.

Chromatin structure is not fixed. Instead, chromatin is dynamic and is subject to extensive developmental and age-associated remodeling. In some cases, this remodeling appears to counter the aging and age-associated diseases, such as cancer, and extend organismal lifespan. However, stochastic non-deterministic changes in chromatin structure might, over time, also contribute to the break down of nuclear, cell and tissue function, and consequently aging and age-associated diseases.

Histomorphometry and cortical robusticity of the adult human femur.

PubMed

Miszkiewicz, Justyna Jolanta; Mahoney, Patrick

2018-01-13

Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n = 233) and female (n = 217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

Drosophila transcription factor Tramtrack69 binds MEP1 to recruit the chromatin remodeler NuRD.

PubMed

Reddy, B Ashok; Bajpe, Prashanth Kumar; Bassett, Andrew; Moshkin, Yuri M; Kozhevnikova, Elena; Bezstarosti, Karel; Demmers, Jeroen A A; Travers, Andrew A; Verrijzer, C Peter

2010-11-01

ATP-dependent chromatin-remodeling complexes (remodelers) are essential regulators of chromatin structure and gene transcription. How remodelers can act in a gene-selective manner has remained enigmatic. A yeast two-hybrid screen for proteins binding the Drosophila transcription factor Tramtrack69 (TTK69) identified MEP1. Proteomic characterization revealed that MEP1 is a tightly associated subunit of the NuRD remodeler, harboring the Mi2 enzymatic core ATPase. In addition, we identified the fly homolog of human Deleted in oral cancer 1 (DOC1), also known as CDK2-associated protein 1 (CDK2AP1), as a bona fide NuRD subunit. Biochemical and genetic assays supported the functional association between MEP1, Mi2, and TTK69. Genomewide expression analysis established that TTK69, MEP1, and Mi2 cooperate closely to control transcription. The TTK69 transcriptome profile correlates poorly with remodelers other than NuRD, emphasizing the selectivity of remodeler action. On the genes examined, TTK69 is able to bind chromatin in the absence of NuRD, but targeting of NuRD is dependent on TTK69. Thus, there appears to be a hierarchical relationship in which transcription factor binding precedes remodeler recruitment.

Functional Coupling between HIV-1 Integrase and the SWI/SNF Chromatin Remodeling Complex for Efficient in vitro Integration into Stable Nucleosomes

PubMed Central

Lesbats, Paul; Botbol, Yair; Chevereau, Guillaume; Vaillant, Cédric; Calmels, Christina; Arneodo, Alain; Andreola, Marie-Line; Lavigne, Marc; Parissi, Vincent

2011-01-01

Establishment of stable HIV-1 infection requires the efficient integration of the retroviral genome into the host DNA. The molecular mechanism underlying the control of this process by the chromatin structure has not yet been elucidated. We show here that stably associated nucleosomes strongly inhibit in vitro two viral-end integration by decreasing the accessibility of DNA to integrase. Remodeling of the chromatinized template by the SWI/SNF complex, whose INI1 major component interacts with IN, restores and redirects the full-site integration into the stable nucleosome region. These effects are not observed after remodeling by other human remodeling factors such as SNF2H or BRG1 lacking the integrase binding protein INI1. This suggests that the restoration process depends on the direct interaction between IN and the whole SWI/SNF complex, supporting a functional coupling between the remodeling and integration complexes. Furthermore, in silico comparison between more than 40,000 non-redundant cellular integration sites selected from literature and nucleosome occupancy predictions also supports that HIV-1 integration is promoted in the genomic region of weaker intrinsic nucleosome density in the infected cell. Our data indicate that some chromatin structures can be refractory for integration and that coupling between nucleosome remodeling and HIV-1 integration is required to overcome this natural barrier. PMID:21347347

Second harmonic generation imaging as a potential tool for staging pregnancy and predicting preterm birth

NASA Astrophysics Data System (ADS)

Akins, Meredith L.; Luby-Phelps, Katherine; Mahendroo, Mala

2010-03-01

We use second harmonic generation (SHG) microscopy to assess changes in collagen structure of murine cervix during cervical remodeling of normal pregnancy and in a preterm birth model. Visual inspection of SHG images revealed substantial changes in collagen morphology throughout normal gestation. SHG images collected in both the forward and backward directions were analyzed quantitatively for changes in overall mean intensity, forward to backward intensity ratio, collagen fiber size, and porosity. Changes in mean SHG intensity and intensity ratio take place in early pregnancy, suggesting that submicroscopic changes in collagen fibril size and arrangement occur before macroscopic changes become evident. Fiber size progressively increased from early to late pregnancy, while pores between collagen fibers became larger and farther apart. Analysis of collagen features in premature cervical remodeling show that changes in collagen structure are dissimilar from normal remodeling. The ability to quantify multiple morphological features of collagen that characterize normal cervical remodeling and distinguish abnormal remodeling in preterm birth models supports future studies aimed at development of SHG endoscopic devices for clinical assessment of collagen changes during pregnancy in women and for predicting risk of preterm labor which occurs in 12.5% of all pregnancies.

Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor.

PubMed

Wang, H B; Zhang, Y

2001-06-15

Dynamic changes in chromatin structure play an important role in transcription regulation. Recent studies have revealed two mechanisms that alter chromatin structure. One involves ATP-dependent chromatin remodeling, and the other involves acetylation of the core histone tails. We have previously purified and characterized a multi-subunit protein complex, NuRD, which possesses both nucleosome remodeling and histone deacetylase activities. Despite extensive biochemical characterization of the complex, little is known about the functions of its individual components. In this study, we focused on Mi2, a component of the NuRD complex. We found that, similar to the native NuRD complex, recombinant Mi2 is a DNA-dependent, nucleosome-stimulated ATPase. Kinetic analysis of the ATP hydrolysis reaction indicated that the differential stimulation of the Mi2 ATPase by DNA and nucleosomes were primarily due to their differential effects on the turnover number of the reaction. Furthermore, we demonstrated that recombinant Mi2 is an efficient nucleosome remodeling factor when compared to that of the native NuRD complex. Our results define the biochemical function of Mi2 and set the stage for understanding the mechanism of nucleosome remodeling in a defined reconstituted system.

Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor

PubMed Central

Wang, Heng-Bin; Zhang, Yi

2001-01-01

Dynamic changes in chromatin structure play an important role in transcription regulation. Recent studies have revealed two mechanisms that alter chromatin structure. One involves ATP-dependent chromatin remodeling, and the other involves acetylation of the core histone tails. We have previously purified and characterized a multi-subunit protein complex, NuRD, which possesses both nucleosome remodeling and histone deacetylase activities. Despite extensive biochemical characterization of the complex, little is known about the functions of its individual components. In this study, we focused on Mi2, a component of the NuRD complex. We found that, similar to the native NuRD complex, recombinant Mi2 is a DNA-dependent, nucleosome-stimulated ATPase. Kinetic analysis of the ATP hydrolysis reaction indicated that the differential stimulation of the Mi2 ATPase by DNA and nucleosomes were primarily due to their differential effects on the turnover number of the reaction. Furthermore, we demonstrated that recombinant Mi2 is an efficient nucleosome remodeling factor when compared to that of the native NuRD complex. Our results define the biochemical function of Mi2 and set the stage for understanding the mechanism of nucleosome remodeling in a defined reconstituted system. PMID:11410659

The angiotensin receptor blocker losartan reduces coronary arteriole remodeling in type 2 diabetic mice.

PubMed

Husarek, Kathryn E; Katz, Paige S; Trask, Aaron J; Galantowicz, Maarten L; Cismowski, Mary J; Lucchesi, Pamela A

2016-01-01

Cardiovascular complications are a leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM) and are associated with alterations of blood vessel structure and function. Although endothelial dysfunction and aortic stiffness have been documented, little is known about the effects of T2DM on coronary microvascular structural remodeling. The renin-angiotensin-aldosterone system plays an important role in large artery stiffness and mesenteric vessel remodeling in hypertension and T2DM. The goal of this study was to determine whether the blockade of AT1R signaling dictates vascular smooth muscle growth that partially underlies coronary arteriole remodeling in T2DM. Control and db/db mice were given AT1R blocker losartan via drinking water for 4 weeks. Using pressure myography, we found that coronary arterioles from 16-week db/db mice undergo inward hypertrophic remodeling due to increased wall thickness and wall-to-lumen ratio with a decreased lumen diameter. This remodeling was accompanied by decreased elastic modulus (decreased stiffness). Losartan treatment decreased wall thickness, wall-to-lumen ratio, and coronary arteriole cell number in db/db mice. Losartan treatment did not affect incremental elastic modulus. However, losartan improved coronary flow reserve. Our data suggest that Ang II-AT1R signaling mediates, at least in part, coronary arteriole inward hypertrophic remodeling in T2DM without affecting vascular mechanics, further suggesting that targeting the coronary microvasculature in T2DM may help reduce cardiac ischemic events. Copyright © 2015 Elsevier Inc. All rights reserved.

Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions

PubMed Central

Pellman, Jason; Sheikh, Farah

2017-01-01

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting 1% to 2% of the general population. It is characterized by rapid and disorganized atrial activation leading to impaired atrial function, which can be diagnosed on an EKG by lack of a P-wave and irregular QRS complexes. AF is associated with increased morbidity and mortality and is a risk factor for embolic stroke and worsening heart failure. Current research on AF support and explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria, either specifically as in lone AF or secondary to other heart disease as in heart failure-associated AF. Remodeling in AF can be grouped into three categories that include: (i) electrical remodeling, which includes modulation of L-type Ca2+ current, various K+ currents and gap junction function; (ii) structural remodeling, which includes changes in tissues properties, size, and ultrastructure; and (iii) autonomic remodeling, including altered sympathovagal activity and hyperinnervation. Electrical, structural, and autonomic remodeling all contribute to creating an AF-prone substrate which is able to produce AF-associated electrical phenomena including a rapidly firing focus, complex multiple reentrant circuit or rotors. Although various remodeling events occur in AF, current AF therapies focus on ventricular rate and rhythm control strategies using pharmacotherapy and surgical interventions. Recent progress in the field has started to focus on the underlying substrate that drives and maintains AF (termed upstream therapies); however, much work is needed in this area. Here, we review current knowledge of AF mechanisms, therapies, and new areas of investigation. PMID:25880508

Evaluation of structural remodeling of the atria with OCT in a chronic rat model of myocardial infarction (Conference Presentation)

NASA Astrophysics Data System (ADS)

Eberle, Melissa M.; Thorn, Stephanie; Young, Lawerence; Pfau, Daniel; Madwed, Jeffrey; Small, Kersten; Kilmas, Michael; Choma, Michael A.; Sinusas, Albert J.

2017-02-01

Atrial fibrillation (AF) occurs following myocardial infarction (MI) and is associated with left ventricular dysfunction, which promotes the development of atrial remodeling and permanent atrial fibrosis. The purpose of this study was determining the effects of MI on left atrial (LA) remodeling with and without therapy with an angiotensin converting enzyme inhibition (ACEi) utilizing optical coherence tomography (OCT). As the composition of the myocardial tissue changes during LA remodeling the optical attenuation of the light will also change providing a metric to quantify the structural remodeling process. Lewis rats (240-275 g) underwent either surgical ligation of left coronary artery creating chronic MI, or SHAM surgery. 13 weeks post-surgery, ex vivo OCT imaging was performed of the LA appendage. Depth-resolved, attenuation coefficient volumes were calculated and the resulting atrial wall attenuation values were analyzed for four experimental groups: SHAM, SHAM with ACEi, MI no ACEi, and MI with ACEi. Quantification of tissue attenuation was performed and shown to significantly increase with MI in association with increases in collagen as verified with corresponding histological sectioning. Fractal analysis of the LA wall trabeculation patterns, 100 µm below the surface, was performed to quantify wall thickening associated with LA remodeling. A significant increase in fractal dimension was determined post MI compared to SHAM corresponding to a loss of the trabeculation pattern and wall thickening. The results from this study demonstrate OCT as an imaging technique capable of investigate LA remodeling with high resolution and label-free optical contrast processing.

Imaging the ovary.

PubMed

Feng, Yi; Tamadon, Amin; Hsueh, Aaron J W

2018-05-01

During each reproductive cycle, the ovary exhibits tissue remodelling and cyclic vasculature changes associated with hormonally regulated folliculogenesis, follicle rupture, luteal formation and regression. However, the relationships among different types of follicles and corpora lutea are unclear, and the role of ovarian vasculature in folliculogenesis and luteal dynamics has not been extensively investigated. Understanding of ovarian physiology and pathophysiology relies upon elucidation of ovarian morphology and architecture. This paper summarizes the literature on traditional approaches to the imaging of ovarian structures and discusses recent advances in ovarian imaging. Traditional in-vivo ultrasound, together with histological and electron microscopic approaches provide detailed views of the ovary at organ, tissue and molecular levels. However, in-vivo imaging is limited to antral and larger follicles whereas histological imaging is mainly two-dimensional in nature. Also discussed are emerging approaches in the use of near-infrared fluorophores to image follicles in live animals to detect preantral follicles as well as visualizing ovarian structures using CLARITY in fixed whole ovaries to elucidate three-dimensional interrelationships among follicles, corpora lutea and ovarian vasculature. Advances in ovarian imaging techniques provide new understanding of ovarian physiology and allow for the development of better tools to diagnose ovarian pathophysiology. Copyright © 2018 Reproductive Healthcare Ltd. All rights reserved.

Osteonic organization of limb bones in mammals, including humans, and birds: a preliminary study.

PubMed

Castrogiovanni, Paola; Imbesi, Rosa; Fisichella, Marco; Mazzone, Venera

2011-01-01

As it is well known, bone tissue is characterized by a calcified extracellular matrix which makes this tissue suitable to support the body and protect the inner organs. Lamellar bone tissue is organized in lamellae, 3-7 microm in thickness, and arranged concentrically around vascular channels: the basic structure in this type of organization is called Haversian system or osteon and the diameter of osteons depends on the number of lamellae. Shape and regional density of osteons are related to the bone segment and the specific functional requirements to meet. Aim of this study is to correlate the compact bone tissue microstructure in various classes of mammals, including humans, and birds in order to find an adequate identification key. The results of our study show that in bone tissue samples from various classes of mammals, including humans, and birds the osteonic structure shows peculiar features, often depending on the rate of bone remodelling, different in different animal species. We conclude that a careful microscopic analysis of bone tissue and the characterization of distinctive osteonic features could give a major contribution to forensic medicine to obtain a more reliable recognition of bone findings.

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

PubMed Central

Florencio-Silva, Rinaldo; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

2015-01-01

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling. PMID:26247020

Biophotonics and Bone Biology

NASA Technical Reports Server (NTRS)

Zimmerli, Gregory; Fischer, David; Asipauskas, Marius; Chauhan, Chirag; Compitello, Nicole; Burke, Jamie; Tate, Melissa Knothe

2004-01-01

One of the more serious side effects of extended space flight is an accelerated bone loss. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It is well known that bone remodeling responds to mechanical forces. We are developing two-photon microscopy techniques to study bone tissue and bone cell cultures to better understand the fundamental response mechanism in bone remodeling. Osteoblast and osteoclast cell cultures are being studied, and the goal is to use molecular biology techniques in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) to study the physiology of in-vitro cell cultures in response to various stimuli, such as fluid flow induced shear stress and mechanical stress. We have constructed a two-photon fluorescence microscope for these studies, and are currently incorporating FLIM detection. Current progress will be reviewed. This work is supported by the NASA John Glenn Biomedical Engineering Consortium.

Extracellular Matrix Degradation and Remodeling in Development and Disease

PubMed Central

Lu, Pengfei; Takai, Ken; Weaver, Valerie M.; Werb, Zena

2011-01-01

The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnormal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine. PMID:21917992

HIF-1α and VEGF expression correlates with thrombus remodeling in cases of intravascular papillary endothelial hyperplasia

PubMed Central

Kim, Sunzoo; Jun, Jae Hun; Kim, Jeongshik; Kim, Do Won; Jang, Yong Hyun; Lee, Weon Ju; Chung, Ho Yun; Lee, Seok-Jong

2013-01-01

Intravascular papillary endothelial hyperplasia (IPEH) is histopathologically characterized by endothelium-lined papillary structures encircling an acellular fibrin core. The process of IPEH pathogenesis is unclear. The purpose of our study was to identify histopathological and immunohistochemical characteristics of IPEH to better understand the pathogenesis of this disease. After reviewing microscopic and medical records from Kyungpook National University Hospital, we selected 16 cases of IPEH. Masson’s trichrome and immunohistochemical staining as well as hematoxylin-eosin staining for 16 cases of IPH were performed. Immunohistochemical studies included CD31, CD68, mast cell tryptase, hypoxia-inducible factor-1 (HIF-1α), and vascular endothelial growth factor (VEGF). Sections from all our cases showed three distinct histological regions including a papillary portion with hyalinized fibrous or fibroblastic cores, an area containing an unorganized thrombus, and organization area with an ingrowth of endothelial cells, myofibroblasts, and fibroblasts. In the organization area, HIF-1α-positive cells were identified in the loose connective tissue. Endothelial cells forming vascular channels were negative for HIF-1α while VEGF was highly expressed in both interstitial mononuclear and endothelial cells. In the papillary portion, the cellular cores were strongly positive for both HIF-1α and VEGF, but the acellular cores were negative. Our investigation confirmed that IPEH is a reactive lesion that incidentally arises during the organization process of older thrombi. It was also found that HIF-1α and VEGF expression was dependent on the thrombus remodeling stage in cases of IPEH. PMID:24294378

Lung remodeling in a porcine model of cyanotic congenital heart defect with decreased pulmonary blood flow.

PubMed

Xu, Yaoqiang; Liu, Yinglong; Li, Zhiqiang; Su, Junwu; Li, Gang; Sun, Lizhong

2012-09-01

Hypoperfusion of the pulmonary vascular bed under the condition of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the mechanistic understanding of this disease, we examined the biochemical and morphological changes of the lung in a relevant animal model and provided valuable insights into the underlying mechanisms of the pathogenesis of pulmonary hypotension. A model of congenital heart defect with decreased pulmonary blood flow was implemented into 8 piglets (the cyanosis group). Another 8 piglets underwent a sham operation (the control group). Two months postoperatively, lung biopsy specimens were harvested for the measurement of the expression levels of MMP-2, MMP-9, TIMP-1, VEGF, and type I and type III collagens. Moreover, the light-microscopic morphology, morphometry, and ultrastructure of lobes were examined. Compared to the controls, the histopathological changes of the pulmonary vasculature in the cyanosis group showed evident hypoplasia and degeneration. The expression levels of MMP-2, MMP-9, TIMP-1, VEGF, and type I collagen, as well as the microvessel density, in the cyanosis group were significantly lower than those in the control group, whereas the level of type III collagen in the cyanosis group was significantly higher than that in the control group. The observed morphological changes may represent an adaptive reaction to the prolonged decrease of pulmonary blood flow. The underlying mechanism of lung remodeling may be attributed to the changes in the expression of structural proteins and cytokines in the pulmonary extracellular matrix induced by modulating factors.

Remodeling of Hippocampal Spine Synapses in the Rat Learned Helplessness Model of Depression

PubMed Central

Hajszan, Tibor; Dow, Antonia; Warner-Schmidt, Jennifer L.; Szigeti-Buck, Klara; Sallam, Nermin L.; Parducz, Arpad; Leranth, Csaba; Duman, Ronald S.

2009-01-01

Background Although it has been postulated for many years that depression is associated with loss of synapses, primarily in the hippocampus, and that antidepressants facilitate synapse growth, we still lack ultrastructural evidence that changes in depressive behavior are indeed correlated with structural synaptic modifications. Methods We analyzed hippocampal spine synapses of male rats (n=127) with electron microscopic stereology in association with performance in the learned helplessness paradigm. Results Inescapable footshock (IES) caused an acute and persistent loss of spine synapses in each of CA1, CA3, and dentate gyrus, which was associated with a severe escape deficit in learned helplessness. On the other hand, IES elicited no significant synaptic alterations in motor cortex. A single injection of corticosterone reproduced both the hippocampal synaptic changes and the behavioral responses induced by IES. Treatment of IES-exposed animals for six days with desipramine reversed both the hippocampal spine synapse loss and the escape deficit in learned helplessness. We noted, however, that desipramine failed to restore the number of CA1 spine synapses to nonstressed levels, which was associated with a minor escape deficit compared to nonstressed controls. Shorter, one-day or three-day desipramine treatments, however, had neither synaptic nor behavioral effects. Conclusions These results indicate that changes in depressive behavior are associated with remarkable remodeling of hippocampal spine synapses at the ultrastructural level. Because spine synapse loss contributes to hippocampal dysfunction, this cellular mechanism may be an important component in the neurobiology of stress-related disorders such as depression. PMID:19006787

Structural basis for host membrane remodeling induced by protein 2B of hepatitis A virus.

PubMed

Vives-Adrián, Laia; Garriga, Damià; Buxaderas, Mònica; Fraga, Joana; Pereira, Pedro José Barbosa; Macedo-Ribeiro, Sandra; Verdaguer, Núria

2015-04-01

The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle preceded by an N-terminally curved five-stranded antiparallel β-sheet that displays striking structural similarity to the β-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. No structural information is currently available for the 2B protein of any picornavirus despite it being involved in a critical process in viral factory formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions, can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral 2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genera within the Picornaviridae family. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

PubMed Central

Vives-Adrián, Laia; Garriga, Damià; Buxaderas, Mònica; Fraga, Joana; Pereira, Pedro José Barbosa

2015-01-01

ABSTRACT The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle preceded by an N-terminally curved five-stranded antiparallel β-sheet that displays striking structural similarity to the β-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. IMPORTANCE No structural information is currently available for the 2B protein of any picornavirus despite it being involved in a critical process in viral factory formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions, can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral 2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genera within the Picornaviridae family. PMID:25589659

Ovalbumin-induced allergic inflammation lead to structural alterations in mouse model and protective effects of intranasal curcumin: A comparative study.

PubMed

Subhashini; Chauhan, P S; Singh, R

2016-01-01

Antigen exposure and persistent inflammation leads to structural changes in the asthmatic airways which are collectively termed as "airway remodelling". Presently available asthma medications ameliorate inflammations but are unable to prevent or reverse the airway remodelling process as most of the treatment strategies are only focused on inflammation instead of remodelling. Curcumin, a phytochemical present in the rhizome of Curcuma longa is well known for its anti-inflammatory activity; however, the main drawback is its poor bioavailability which limits its therapeutic approval. So, the effect of nasal curcumin on acute and chronic asthma has been studied where short exposure to ovalbumin (4 days) represents acute phase whereas repeated exposures for longer (twice per week till 5 weeks) represents chronic asthma. Disodium cromoglycate (DSCG, 50mg/kg, i.p.) and dexamethasone (1mg/kg, i.p.) were used as standard drugs in acute and chronic model of asthma respectively. OVA-induced airway inflammation initiated in acute stage led to remodelling due to persistent inflammation, epithelial and sub epithelial thickening (smooth muscle thickening), extracellular matrix (ECM) deposition, goblet cell hyperplasia and mucus plug formation. Intranasal curcumin is effective in inhibiting airway inflammation and remodelling both by maintaining the structural integrity of lungs in terms of inflammation, airway wall thickening and mucus production. Our findings suggest that curcumin administered through nasal route might prove therapeutically efficient in inhibiting allergic airway inflammations and maintaining structural integrity in the mouse model of allergic asthma. This may lead to the development of curcumin aerosol in near future. Copyright © 2016 SEICAP. Published by Elsevier Espana. All rights reserved.

Second harmonic generation microscopy differentiates collagen type I and type III in COPD

NASA Astrophysics Data System (ADS)

Suzuki, Masaru; Kayra, Damian; Elliott, W. Mark; Hogg, James C.; Abraham, Thomas

2012-03-01

The structural remodeling of extracellular matrix proteins in peripheral lung region is an important feature in chronic obstructive pulmonary disease (COPD). Multiphoton microscopy is capable of inducing specific second harmonic generation (SHG) signal from non-centrosymmetric structural proteins such as fibrillar collagens. In this study, SHG microscopy was used to examine structural remodeling of the fibrillar collagens in human lungs undergoing emphysematous destruction (n=2). The SHG signals originating from these diseased lung thin sections from base to apex (n=16) were captured simultaneously in both forward and backward directions. We found that the SHG images detected in the forward direction showed well-developed and well-structured thick collagen fibers while the SHG images detected in the backward direction showed striking different morphological features which included the diffused pattern of forward detected structures plus other forms of collagen structures. Comparison of these images with the wellestablished immunohistochemical staining indicated that the structures detected in the forward direction are primarily the thick collagen type I fibers and the structures identified in the backward direction are diffusive structures of forward detected collagen type I plus collagen type III. In conclusion, we here demonstrate the feasibility of SHG microscopy in differentiating fibrillar collagen subtypes and understanding their remodeling in diseased lung tissues.

Drosophila Transcription Factor Tramtrack69 Binds MEP1 To Recruit the Chromatin Remodeler NuRD ▿ †

PubMed Central

Reddy, B. Ashok; Bajpe, Prashanth Kumar; Bassett, Andrew; Moshkin, Yuri M.; Kozhevnikova, Elena; Bezstarosti, Karel; Demmers, Jeroen A. A.; Travers, Andrew A.; Verrijzer, C. Peter

2010-01-01

ATP-dependent chromatin-remodeling complexes (remodelers) are essential regulators of chromatin structure and gene transcription. How remodelers can act in a gene-selective manner has remained enigmatic. A yeast two-hybrid screen for proteins binding the Drosophila transcription factor Tramtrack69 (TTK69) identified MEP1. Proteomic characterization revealed that MEP1 is a tightly associated subunit of the NuRD remodeler, harboring the Mi2 enzymatic core ATPase. In addition, we identified the fly homolog of human Deleted in oral cancer 1 (DOC1), also known as CDK2-associated protein 1 (CDK2AP1), as a bona fide NuRD subunit. Biochemical and genetic assays supported the functional association between MEP1, Mi2, and TTK69. Genomewide expression analysis established that TTK69, MEP1, and Mi2 cooperate closely to control transcription. The TTK69 transcriptome profile correlates poorly with remodelers other than NuRD, emphasizing the selectivity of remodeler action. On the genes examined, TTK69 is able to bind chromatin in the absence of NuRD, but targeting of NuRD is dependent on TTK69. Thus, there appears to be a hierarchical relationship in which transcription factor binding precedes remodeler recruitment. PMID:20733004

CorMatrix valved conduit in a porcine model: long-term remodelling and biomechanical characterization.

PubMed

Mosala Nezhad, Zahra; Poncelet, Alain; de Kerchove, Laurent; Fervaille, Caroline; Banse, Xavier; Bollen, Xavier; Dehoux, Jean-Paul; El Khoury, Gebrine; Gianello, Pierre

2017-01-01

Porcine small intestinal submucosa extracellular matrix (CorMatrix; CorMatrix Cardiovascular, Rosewell, GA) is a relatively novel tissue substitute used in cardiovascular applications. We investigated the biological reaction and remodelling of CorMatrix as a tri-leaflet valved conduit in a pig model. We hypothesized that CorMatrix maintains a durable architecture as a valved conduit and remodels to resemble surrounding tissues. We fashioned the valved conduit using a 7 × 10 cm 4-ply CorMatrix sheet and placed it in the thoracic aorta of seven landrace pigs for 3, 4, 5 and 6 months. Biodegradation, replacement by native tissue, strength and durability were examined by histology, immunohistochemistry and mechanical testing. Four pigs, one per time frame, completed the study. The conduit lost its original architecture as a tri-leaflet valve due to cusp immobility, subsequent attachment to the wall segment and consequent maintenance of a thick arterial wall-like structure. Scaffold resorption was incomplete, with disorganized inconsistent spatial and temporal degradation even at 6 months. Fibrosis, scarring and calcification started at 4 months and chronic inflammation persisted. The partially remodelled scaffold did not resemble the aortic wall, suggesting impaired remodelling. Mechanical testing showed progressive weakening of the tissues over time, which were liable to breakage. CorMatrix is biodegradable; however, it failed to remodel in a structured and anatomical fashion in an arterial environment. Progressive mechanical and remodelling failure in this scenario might be explained by the complexity of the conduit design and the host's chronic inflammatory response, leading to early fibrosis and calcification. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Reverse right ventricular structural and extracellular matrix remodeling by estrogen in severe pulmonary hypertension

PubMed Central

Nadadur, Rangarajan D.; Umar, Soban; Wong, Gabriel; Eghbali, Mansour; Iorga, Andrea; Matori, Humann; Partow-Navid, Rod

2012-01-01

Chronic pulmonary hypertension (PH) leads to right-ventricular failure (RVF) characterized by RV remodeling. Ventricular remodeling is emerging as an important process during heart failure and recovery. Remodeling in RVF induced by PH is not fully understood. Recently we discovered that estrogen (E2) therapy can rescue severe preexisting PH. Here, we focused on whether E2 (42.5 μg·kg−1·day−1, 10 days) can reverse adverse RV structural and extracellular matrix (ECM) remodeling induced by PH using monocrotaline (MCT, 60 mg/kg). RV fibrosis was evident in RVF males. Intact females developed less severe RV remodeling compared with males and ovariectomized (OVX) females. Novel ECM-degrading disintegrin-metalloproteinases ADAM15 and ADAM17 transcripts were elevated ∼2-fold in all RVF animals. E2 therapy reversed RV remodeling in all groups. In vitro, E2 directly inhibited ANG II-induced expression of fibrosis markers as well as the metalloproteinases in cultured cardiac fibroblasts. Estrogen receptor-β agonist diarylpropionitrile (DPN) but not estrogen receptor-α agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) was as effective as E2 in inhibiting expression of these genes. Expression of ECM-interacting cardiac fetal-gene osteopontin (OPN) also increased ∼9-fold in RVF males. Intact females were partially protected from OPN upregulation (∼2-fold) but OVX females were not. E2 reversed OPN upregulation in all groups. Upregulation of OPN was also reversed in vitro by E2. Plasma OPN was elevated in RVF (∼1.5-fold) and decreased to control levels in the E2 group. RVF resulted in elevated Akt phosphorylation, but not ERK, in the RV, and E2 therapy restored Akt phosphorylation. In conclusion, E2 therapy reverses adverse RV remodeling associated with PH by reversing fibrosis and upregulation of novel ECM enzymes ADAM15, ADAM17, and OPN. These effects are likely mediated through estrogen receptor-β. PMID:22628376

A Rhizobium leguminosarum CHDL- (Cadherin-Like-) Lectin Participates in Assembly and Remodeling of the Biofilm Matrix

PubMed Central

Vozza, Nicolás F.; Abdian, Patricia L.; Russo, Daniela M.; Mongiardini, Elías J.; Lodeiro, Aníbal R.; Molin, Søren; Zorreguieta, Angeles

2016-01-01

In natural environments most bacteria live in multicellular structures called biofilms. These cell aggregates are enclosed in a self-produced polymeric extracellular matrix, which protects the cells, provides mechanical stability and mediates cellular cohesion and adhesion to surfaces. Although important advances were made in the identification of the genetic and extracellular factors required for biofilm formation, the mechanisms leading to biofilm matrix assembly, and the roles of extracellular proteins in these processes are still poorly understood. The symbiont Rhizobium leguminosarum requires the synthesis of the acidic exopolysaccharide and the PrsDE secretion system to develop a mature biofilm. PrsDE is responsible for the secretion of the Rap family of proteins that share one or two Ra/CHDL (cadherin-like-) domains. RapA2 is a calcium-dependent lectin with a cadherin-like β sheet structure that specifically recognizes the exopolysaccharide, either as a capsular polysaccharide (CPS) or in its released form [extracellular polysaccharide (EPS)]. In this study, using gain and loss of function approaches combined with phenotypic and microscopic studies we demonstrated that RapA lectins are involved in biofilm matrix development and cellular cohesion. While the absence of any RapA protein increased the compactness of bacterial aggregates, high levels of RapA1 expanded distances between cells and favored the production of a dense matrix network. Whereas endogenous RapA(s) are predominantly located at one bacterial pole, we found that under overproduction conditions, RapA1 surrounded the cell in a way that was reminiscent of the capsule. Accordingly, polysaccharide analyses showed that the RapA lectins promote CPS formation at the expense of lower EPS production. Besides, polysaccharide analysis suggests that RapA modulates the EPS size profile. Collectively, these results show that the interaction of RapA lectins with the polysaccharide is involved in rhizobial biofilm matrix assembly and remodeling. PMID:27790205

3D-Reconstructions and Virtual 4D-Visualization to Study Metamorphic Brain Development in the Sphinx Moth Manduca Sexta

PubMed Central

Huetteroth, Wolf; el Jundi, Basil; el Jundi, Sirri; Schachtner, Joachim

2009-01-01

During metamorphosis, the transition from the larva to the adult, the insect brain undergoes considerable remodeling: new neurons are integrated while larval neurons are remodeled or eliminated. One well acknowledged model to study metamorphic brain development is the sphinx moth Manduca sexta. To further understand mechanisms involved in the metamorphic transition of the brain we generated a 3D standard brain based on selected brain areas of adult females and 3D reconstructed the same areas during defined stages of pupal development. Selected brain areas include for example mushroom bodies, central complex, antennal- and optic lobes. With this approach we eventually want to quantify developmental changes in neuropilar architecture, but also quantify changes in the neuronal complement and monitor the development of selected neuronal populations. Furthermore, we used a modeling software (Cinema 4D) to create a virtual 4D brain, morphing through its developmental stages. Thus the didactical advantages of 3D visualization are expanded to better comprehend complex processes of neuropil formation and remodeling during development. To obtain datasets of the M. sexta brain areas, we stained whole brains with an antiserum against the synaptic vesicle protein synapsin. Such labeled brains were then scanned with a confocal laser scanning microscope and selected neuropils were reconstructed with the 3D software AMIRA 4.1. PMID:20339481

3D-Reconstructions and Virtual 4D-Visualization to Study Metamorphic Brain Development in the Sphinx Moth Manduca Sexta.

PubMed

Huetteroth, Wolf; El Jundi, Basil; El Jundi, Sirri; Schachtner, Joachim

2010-01-01

DURING METAMORPHOSIS, THE TRANSITION FROM THE LARVA TO THE ADULT, THE INSECT BRAIN UNDERGOES CONSIDERABLE REMODELING: new neurons are integrated while larval neurons are remodeled or eliminated. One well acknowledged model to study metamorphic brain development is the sphinx moth Manduca sexta. To further understand mechanisms involved in the metamorphic transition of the brain we generated a 3D standard brain based on selected brain areas of adult females and 3D reconstructed the same areas during defined stages of pupal development. Selected brain areas include for example mushroom bodies, central complex, antennal- and optic lobes. With this approach we eventually want to quantify developmental changes in neuropilar architecture, but also quantify changes in the neuronal complement and monitor the development of selected neuronal populations. Furthermore, we used a modeling software (Cinema 4D) to create a virtual 4D brain, morphing through its developmental stages. Thus the didactical advantages of 3D visualization are expanded to better comprehend complex processes of neuropil formation and remodeling during development. To obtain datasets of the M. sexta brain areas, we stained whole brains with an antiserum against the synaptic vesicle protein synapsin. Such labeled brains were then scanned with a confocal laser scanning microscope and selected neuropils were reconstructed with the 3D software AMIRA 4.1.

Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4.

PubMed

Morra, Rosa; Lee, Benjamin M; Shaw, Heather; Tuma, Roman; Mancini, Erika J

2012-07-30

CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which provide a structural explanation for the regulation of CHD4 activities by intramolecular domain communication. Our results demonstrate functional interdependency between domains within a chromatin remodeller. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Executive summary.

Treesearch

David B. McKeever

1997-01-01

The repair and remodeling of residential units in the existing housing stock is an important market for wood products. Included are many, and varied repair and remodeling activities and projects, some of which require substantial amounts of wood products, some of which do not. Currently, about 24 percent of all lumber, 23 percent of all structural panels, 15 percent of...

CREB Selectively Controls Learning-Induced Structural Remodeling of Neurons

ERIC Educational Resources Information Center

Middei, Silvia; Spalloni, Alida; Longone, Patrizia; Pittenger, Christopher; O'Mara, Shane M.; Marie, Helene; Ammassari-Teule, Martine

2012-01-01

The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons…

Histone H3 Lysine 14 (H3K14) Acetylation Facilitates DNA Repair in a Positioned Nucleosome by Stabilizing the Binding of the Chromatin Remodeler RSC (Remodels Structure of Chromatin)*

PubMed Central

Duan, Ming-Rui; Smerdon, Michael J.

2014-01-01

Histone H3 acetylation is induced by UV damage in yeast and may play an important role in regulating the repair of UV photolesions in nucleosome-loaded genomic loci. However, it remains elusive how H3 acetylation facilitates repair. We generated a strongly positioned nucleosome containing homogeneously acetylated H3 at Lys-14 (H3K14ac) and investigated possible mechanisms by which H3K14 acetylation modulates repair. We show that H3K14ac does not alter nucleosome unfolding dynamics or enhance the repair of UV-induced cyclobutane pyrimidine dimers by UV photolyase. Importantly, however, nucleosomes with H3K14ac have a higher affinity for purified chromatin remodeling complex RSC (Remodels the Structure of Chromatin) and show greater cyclobutane pyrimidine dimer repair compared with unacetylated nucleosomes. Our study indicates that, by anchoring RSC, H3K14 acetylation plays an important role in the unfolding of strongly positioned nucleosomes during repair of UV damage. PMID:24515106

Collagen and the myocardium: fibrillar structure, biosynthesis and degradation in relation to hypertrophy and its regression.

PubMed

Eghbali, M; Weber, K T

1990-07-17

The extracellular matrix of the myocardium contains an elaborate structural matrix composed mainly of fibrillar types I and III collagen. This matrix is responsible for the support and alignment of myocytes and capillaries. Because of its alignment, location, configuration and tensile strength, relative to cardiac myocytes, the collagen matrix represents a major determinant of myocardial stiffness. Cardiac fibroblasts, not myocytes, contain the mRNA for these fibrillar collagens. In the hypertrophic remodeling of the myocardium that accompanies arterial hypertension, a progressive structural and biochemical remodeling of the matrix follows enhanced collagen gene expression. The resultant significant accumulation of collagen in the interstitium and around intramyocardial coronary arteries, or interstitial and perivascular fibrosis, represents a pathologic remodeling of the myocardium that compromises this normally efficient pump. This report reviews the structural nature, biosynthesis and degradation of collagen in the normal and hypertrophied myocardium. It suggests that interstitial heart disease, or the disproportionate growth of the extracellular matrix relative to myocyte hypertrophy, is an entity that merits greater understanding, particularly the factors regulating types I and III collagen gene expression and their degradation.

Childhood obesity and cardiac remodeling: from cardiac structure to myocardial mechanics.

PubMed

Tadic, Marijana; Cuspidi, Cesare

2015-08-01

Epidemic of obesity, especially morbid obesity, among children and adolescents, is a key factor associated with the dramatic increase in prevalence of type 2 diabetes mellitus, arterial hypertension, and metabolic syndrome in this population. Furthermore, childhood obesity represents a very important predictor of obesity in adulthood that is related to cardiovascular and cerebrovascular diseases. Overweight and obesity in children and adolescents are associated with impairment of cardiac structure and function. The majority of studies investigated the influence of obesity on left ventricular remodeling. However, the impact of obesity on the right ventricle, both the atria, and myocardial mechanics has been insufficiently studied. The aim of this review article is to summarize all data about heart remodeling in childhood, from cardiac size, throughout systolic and diastolic function, to myocardial mechanics, using a wide range of mainly echocardiographic techniques and parameters. Additionally, we sought to present current knowledge about the influence of weight loss, achieved by various therapeutic approaches, on the improvement of cardiac geometry, structure, and function in obese children and adolescents.

Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease

PubMed Central

Hunt, James M.; Bethea, Brian; Liu, Xiang; Gandjeva, Aneta; Mammen, Pradeep P. A.; Stacher, Elvira; Gandjeva, Marina R.; Parish, Elisabeth; Perez, Mario; Smith, Lynelle; Graham, Brian B.; Kuebler, Wolfgang M.

2013-01-01

Despite the importance of pulmonary veins in normal lung physiology and the pathobiology of pulmonary hypertension with left heart disease (PH-LHD), pulmonary veins remain largely understudied. Difficult to identify histologically, lung venous endothelium or smooth muscle cells display no unique characteristic functional and structural markers that distinguish them from pulmonary arteries. To address these challenges, we undertook a search for unique molecular markers in pulmonary veins. In addition, we addressed the expression pattern of a candidate molecular marker and analyzed the structural pattern of vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung tissue of patients with PH-LHD obtained at time of placement on a left ventricular assist device. We detected urokinase plasminogen activator receptor (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with PH-LHD; however, we also detected induction of uPAR expression in remodeled pulmonary arteries. These findings were validated in lungs of patients with PH-LHD. In selected patients with sequential lung biopsy at the time of removal of the left ventricular assist device, we present early data suggesting improvement in pulmonary hemodynamics and venous remodeling, indicating potential regression of venous remodeling in response to assist device treatment. Our data indicate that remodeling of pulmonary veins is an integral part of PH-LHD and that pulmonary veins share some key features present in remodeled yet not normotensive pulmonary arteries. PMID:24039255

Effect of Brain-Derived Neurotrophic Factor Haploinsufficiency on Stress-Induced Remodeling of Hippocampal Neurons

PubMed Central

Magariños, A.M.; Li, C.J.; Toth, J. Gal; Bath, K.G.; Jing, D.; Lee, F.S.; McEwen, B.S.

2010-01-01

Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the hippocampus and released from neurons in an activity-dependent manner, as a mediator of the stress-induced dendritic remodeling. The analysis of Golgi-impregnated hippocampal sections revealed that wild type (WT) C57BL/6 male mice showed a similar CA3 apical dendritic remodeling in response to three weeks of CRS to that previously described for rats. Haploinsufficient BDNF mice (BDNF±) did not show such remodeling, but, even without CRS, they presented shorter and simplified CA3 apical dendritic arbors, like those observed in stressed WT mice. Furthermore, unstressed BDNF± mice showed a significant decrease in total hippocampal volume. The dendritic arborization of CA1 pyramidal neurons was not affected by CRS or genotype. However, only in WT mice, CRS induced changes in the density of dendritic spine shape subtypes in both CA1 and CA3 apical dendrites. These results suggest a complex role of BDNF in maintaining the dendritic and spine morphology of hippocampal neurons and the associated volume of the hippocampal formation. The inability of CRS to modify the dendritic structure of CA3 pyramidal neurons in BDNF± mice suggests an indirect, perhaps permissive, role of BDNF in mediating hippocampal dendritic remodeling. PMID:20095008

New aspects of vascular remodelling: the involvement of all vascular cell types.

PubMed

McGrath, John C; Deighan, Clare; Briones, Ana M; Shafaroudi, Majid Malekzadeh; McBride, Melissa; Adler, Jeremy; Arribas, Silvia M; Vila, Elisabet; Daly, Craig J

2005-07-01

Conventionally, the architecture of arteries is based around the close-packed smooth muscle cells and extracellular matrix. However, the adventitia and endothelium are now viewed as key players in vascular growth and repair. A new dynamic picture has emerged of blood vessels in a constant state of self-maintenance. Recent work raises fundamental questions about the cellular heterogeneity of arteries and the time course and triggering of normal and pathological remodelling. A common denominator emerging in hypertensive remodelling is an early increase in adventitial cell density suggesting that adventitial cells drive remodelling and may initiate subsequent changes such as re-arrangement of smooth muscle cells and extracellular matrix. The organization of vascular smooth muscle cells follows regular arrangements that can be modelled mathematically. In hypertension, new patterns can be quantified in these terms and give insights to how structure affects function. As with smooth muscle, little is known about the organization of the vascular endothelium, or its role in vascular remodelling. Current observations suggest that there may be a close relationship between the helical organization of smooth muscle cells and the underlying pattern of endothelial cells. The function of myoendothelial connections is a topic of great current interest and may relate to the structure of the internal elastic lamina through which the connections must pass. In hypertensive remodelling this must present an organizational challenge. The objective of this paper is to show how the functions of blood vessels depend on their architecture and a continuous interaction of different cell types and extracellular proteins.

Adaptive remodeling of the biliary tree: the essence of liver progenitor cell expansion.

PubMed

Kok, Cindy Yuet-Yin; Miyajima, Atsushi; Itoh, Tohru

2015-07-01

The liver progenitor cell population has long been thought to exist within the liver. However, there are no standardized criteria for defining the liver progenitor cells, and there has been intense debate about the origin of these cells in the adult liver. The characteristics of such cells vary depending on the disease model used and also on the method of analysis. Visualization of three-dimensional biliary structures has revealed that the emergence of liver progenitor cells essentially reflects the adaptive remodeling of the hepatic biliary network in response to liver injury. We propose that the progenitor cell exists as a subpopulation in the biliary tree and show that the appearance of liver progenitor cells in injured parenchyma is reflective of extensive remodeling of the biliary structure. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Minor Groove Binder Distamycin Remodels Chromatin but Inhibits Transcription

PubMed Central

Majumder, Parijat; Banerjee, Amrita; Shandilya, Jayasha; Senapati, Parijat; Chatterjee, Snehajyoti; Kundu, Tapas K.; Dasgupta, Dipak

2013-01-01

The condensed structure of chromatin limits access of cellular machinery towards template DNA. This in turn represses essential processes like transcription, replication, repair and recombination. The repression is alleviated by a variety of energy dependent processes, collectively known as “chromatin remodeling”. In a eukaryotic cell, a fine balance between condensed and de-condensed states of chromatin helps to maintain an optimum level of gene expression. DNA binding small molecules have the potential to perturb such equilibrium. We present herein the study of an oligopeptide antibiotic distamycin, which binds to the minor groove of B-DNA. Chromatin mobility assays and circular dichroism spectroscopy have been employed to study the effect of distamycin on chromatosomes, isolated from the liver of Sprague-Dawley rats. Our results show that distamycin is capable of remodeling both chromatosomes and reconstituted nucleosomes, and the remodeling takes place in an ATP-independent manner. Binding of distamycin to the linker and nucleosomal DNA culminates in eviction of the linker histone and the formation of a population of off-centered nucleosomes. This hints at a possible corkscrew type motion of the DNA with respect to the histone octamer. Our results indicate that distamycin in spite of remodeling chromatin, inhibits transcription from both DNA and chromatin templates. Therefore, the DNA that is made accessible due to remodeling is either structurally incompetent for transcription, or bound distamycin poses a roadblock for the transcription machinery to advance. PMID:23460895

Wood products used for residential repair and remodeling in the United States, 1991

Treesearch

D. B. McKeever; R. G. Anderson

Large amounts of lumber and wood panel products are used annually for the repair and remodeling of residential structures and properties in the United States. In response to the need by government and industry for detailed information on this important market for timber products, a study was conducted by the Timber Demand and Technology...

Early inhibitory effects of zoledronic acid in tooth extraction sockets in dogs are negated by recombinant human bone morphogenetic protein.

PubMed

Gerard, David A; Carlson, Eric R; Gotcher, Jack E; Pickett, David O

2014-01-01

This study was conducted with 2 purposes. The first was to determine the effect of a single dose of zoledronic acid (ZA) on the healing of a tooth extraction socket in dogs. The second was to determine if placement of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) - INFUSE, (Medtronic, Memphis, TN) into these extraction sockets would inhibit the inhibition on bone healing and remodeling by ZA. Nine adult female beagle dogs (2 to 3 yr old) were placed into 3 groups of 3 dogs each. Group I received 15 mL of sterile saline intravenously; group II received 2.5 mg of ZA intravenously; and group III received 5 mg of ZA intravenously. Forty-five days after treatment, all dogs underwent extraction of noncontiguous right and left mandibular first molars and second premolars. In group I, the right mandibular extraction sockets had nothing placed in them, whereas the left mandibular sockets had only ACS placed in them. In groups II and III, the right mandibular sockets had rhBMP-2/ACS placed in them, whereas the left mandibular sockets had only ACS placed. All extraction sockets were surgically closed. Tetracycline was given intravenously 5 and 12 days later, and all animals were euthanized 15 days after tooth extraction. The extraction sockets and rib and femur samples were harvested immediately after euthanasia, processed, and studied microscopically. A single dose of ZA significantly inhibited healing and bone remodeling in the area of the tooth extractions. The combination of rhBMP-2/ACS appeared to over-ride some of the bone remodeling inhibition of the ZA and increased bone fill in the extraction sites, and remodeling activity in the area was noted. The effects of rhBMP-2/ACS were confined to the area of the extraction sockets because bone activity at distant sites was not influenced. A single dose of ZA administered intravenously inhibits early healing of tooth extraction sockets and bone remodeling in this animal model. The combination of rhBMP-2/ACS significantly increased bone fill and bone remodeling in these areas, negating much of the effect of the ZA. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Osteo-odonto-keratoprosthesis: a human model of autotransplant.

PubMed

Pecorella, Irene; Taloni, Maurizio; Ciardi, Antonio; Alexander, Robert A; Falcinelli, Giancarlo

2006-10-01

We evaluated the microscopical changes that occurred when bone and dental tissue were exposed to such a foreign environment as the ocular surface and anterior chamber in 17 osteo-odonto-keratoprostheses removed from the recipient's eye after 1 to 20 years. Histochemical methods were performed to demonstrate elastic and precursor fibers, while immunohistochemical procedures were used to study the distribution of collagen types I to VI. Islands of heterotopic, newly formed bone were observed in the dentin and the periodontal space, leading to focal dentoalveolar ankylosis. Remodelling and disappearance of the periodontal ligament was never diffuse.

A magnesium-induced triplex pre-organizes the SAM-II riboswitch

PubMed Central

Roy, Susmita; Lammert, Heiko; Dayie, T. Kwaku; Sanbonmatsu, Karissa Y.

2017-01-01

Our 13C- and 1H-chemical exchange saturation transfer (CEST) experiments previously revealed a dynamic exchange between partially closed and open conformations of the SAM-II riboswitch in the absence of ligand. Here, all-atom structure-based molecular simulations, with the electrostatic effects of Manning counter-ion condensation and explicit magnesium ions are employed to calculate the folding free energy landscape of the SAM-II riboswitch. We use this analysis to predict that magnesium ions remodel the landscape, shifting the equilibrium away from the extended, partially unfolded state towards a compact, pre-organized conformation that resembles the ligand-bound state. Our CEST and SAXS experiments, at different magnesium ion concentrations, quantitatively confirm our simulation results, demonstrating that magnesium ions induce collapse and pre-organization. Agreement between theory and experiment bolsters microscopic interpretation of our simulations, which shows that triplex formation between helix P2b and loop L1 is highly sensitive to magnesium and plays a key role in pre-organization. Pre-organization of the SAM-II riboswitch allows rapid detection of ligand with high selectivity, which is important for biological function. PMID:28248966

Genetic screen in Drosophila muscle identifies autophagy-mediated T-tubule remodeling and a Rab2 role in autophagy.

PubMed

Fujita, Naonobu; Huang, Wilson; Lin, Tzu-Han; Groulx, Jean-Francois; Jean, Steve; Nguyen, Jen; Kuchitsu, Yoshihiko; Koyama-Honda, Ikuko; Mizushima, Noboru; Fukuda, Mitsunori; Kiger, Amy A

2017-01-07

Transverse (T)-tubules make-up a specialized network of tubulated muscle cell membranes involved in excitation-contraction coupling for power of contraction. Little is known about how T-tubules maintain highly organized structures and contacts throughout the contractile system despite the ongoing muscle remodeling that occurs with muscle atrophy, damage and aging. We uncovered an essential role for autophagy in T-tubule remodeling with genetic screens of a developmentally regulated remodeling program in Drosophila abdominal muscles. Here, we show that autophagy is both upregulated with and required for progression through T-tubule disassembly stages. Along with known mediators of autophagosome-lysosome fusion, our screens uncovered an unexpected shared role for Rab2 with a broadly conserved function in autophagic clearance. Rab2 localizes to autophagosomes and binds to HOPS complex members, suggesting a direct role in autophagosome tethering/fusion. Together, the high membrane flux with muscle remodeling permits unprecedented analysis both of T-tubule dynamics and fundamental trafficking mechanisms.

Exploring photoreceptor reflectivity via multimodal imaging of outer retinal tubulation in advanced age-related macular degeneration

PubMed Central

Litts, Katie M.; Wang, Xiaolin; Clark, Mark E.; Owsley, Cynthia; Freund, K. Bailey; Curcio, Christine A.; Zhang, Yuhua

2016-01-01

Purpose To investigate the microscopic structure of outer retinal tubulation (ORT) and optical properties of cone photoreceptors in vivo, we studied ORT appearance by multimodal imaging, including spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO). Methods Four eyes of 4 subjects with advanced AMD underwent color fundus photography, infrared reflectance imaging, SD-OCT, and AOSLO with a high-resolution research instrument. ORT was identified in closely spaced (11 μm) SD-OCT volume scans. Results ORT in cross-sectional and en face SD-OCT was a hyporeflective area representing a lumen surrounded by a hyperreflective border consisting of cone photoreceptor mitochondria and external limiting membrane, per previous histology. In contrast, ORT by AOSLO was a hyporeflective structure of the same shape as in en face SD-OCT but lacking visualizable cone photoreceptors. Conclusion Lack of ORT cone reflectivity by AOSLO indicates that cones have lost their normal directionality and waveguiding property due to loss of outer segments and subsequent retinal remodeling. Reflective ORT cones by SD-OCT, in contrast, may depend partly on mitochondria as light scatterers within inner segments of these degenerating cells, a phenomenon enhanced by coherent imaging. Multimodal imaging of ORT provides insight into cone degeneration and reflectivity sources in OCT. PMID:27584549

A histological atlas of the tissues and organs of neotenic and metamorphosed axolotl.

PubMed

Demircan, Turan; İlhan, Ayşe Elif; Aytürk, Nilüfer; Yıldırım, Berna; Öztürk, Gürkan; Keskin, İlknur

2016-09-01

Axolotl (Ambystoma Mexicanum) has been emerging as a promising model in stem cell and regeneration researches due to its exceptional regenerative capacity. Although it represents lifelong lasting neoteny, induction to metamorphosis with thyroid hormones (THs) treatment advances the utilization of Axolotl in various studies. It has been reported that amphibians undergo anatomical and histological remodeling during metamorphosis and this transformation is crucial for adaptation to terrestrial conditions. However, there is no comprehensive histological investigation regarding the morphological alterations of Axolotl organs and tissues throughout the metamorphosis. Here, we reveal the histological differences or resemblances between the neotenic and metamorphic axolotl tissues. In order to examine structural features and cellular organization of Axolotl organs, we performed Hematoxylin & Eosin, Luxol-Fast blue, Masson's trichrome, Alcian blue, Orcein and Weigart's staining. Stained samples from brain, gallbladder, heart, intestine, liver, lung, muscle, skin, spleen, stomach, tail, tongue and vessel were analyzed under the light microscope. Our findings contribute to the validation of the link between newly acquired functions and structural changes of tissues and organs as observed in tail, skin, gallbladder and spleen. We believe that this descriptive work provides new insights for a better histological understanding of both neotenic and metamorphic Axolotl tissues. Copyright © 2016 Elsevier GmbH. All rights reserved.

Stimulated Emission Depletion Live-Cell Super-Resolution Imaging Shows Proliferative Remodeling of T-Tubule Membrane Structures After Myocardial Infarction

PubMed Central

Wagner, Eva; Lauterbach, Marcel A.; Kohl, Tobias; Westphal, Volker; Williams, George S.B.; Steinbrecher, Julia H.; Streich, Jan-Hendrik; Korff, Brigitte; Tuan, Hoang-Trong M.; Hagen, Brian; Luther, Stefan; Hasenfuss, Gerd; Parlitz, Ulrich; Jafri, M. Saleet; Hell, Stefan W.; Lederer, W. Jonathan; Lehnart, Stephan E.

2014-01-01

Rationale Transverse tubules (TTs) couple electric surface signals to remote intracellular Ca2+ release units (CRUs). Diffraction-limited imaging studies have proposed loss of TT components as disease mechanism in heart failure (HF). Objectives Objectives were to develop quantitative super-resolution strategies for live-cell imaging of TT membranes in intact cardiomyocytes and to show that TT structures are progressively remodeled during HF development, causing early CRU dysfunction. Methods and Results Using stimulated emission depletion (STED) microscopy, we characterized individual TTs with nanometric resolution as direct readout of local membrane morphology 4 and 8 weeks after myocardial infarction (4pMI and 8pMI). Both individual and network TT properties were investigated by quantitative image analysis. The mean area of TT cross sections increased progressively from 4pMI to 8pMI. Unexpectedly, intact TT networks showed differential changes. Longitudinal and oblique TTs were significantly increased at 4pMI, whereas transversal components appeared decreased. Expression of TT-associated proteins junctophilin-2 and caveolin-3 was significantly changed, correlating with network component remodeling. Computational modeling of spatial changes in HF through heterogeneous TT reorganization and RyR2 orphaning (5000 of 20 000 CRUs) uncovered a local mechanism of delayed subcellular Ca2+ release and action potential prolongation. Conclusions This study introduces STED nanoscopy for live mapping of TT membrane structures. During early HF development, the local TT morphology and associated proteins were significantly altered, leading to differential network remodeling and Ca2+ release dyssynchrony. Our data suggest that TT remodeling during HF development involves proliferative membrane changes, early excitation-contraction uncoupling, and network fracturing. PMID:22723297

Characterizing Brain Structures and Remodeling after TBI Based on Information Content, Diffusion Entropy

PubMed Central

Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P.; Zhang, Zheng Gang; Lehman, Norman L.; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

2013-01-01

Background To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Methods Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Results Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Conclusions Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease. PMID:24143186

Characterizing brain structures and remodeling after TBI based on information content, diffusion entropy.

PubMed

Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P; Zhang, Zheng Gang; Lehman, Norman L; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

2013-01-01

To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease.

The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

PubMed Central

Atochina-Vasserman, Elena N.; Massa, Christopher B.; Birkelbach, Bastian; Guo, Chang-Jiang; Scott, Pamela; Haenni, Beat; Beers, Michael F.; Ochs, Matthias; Gow, Andrew J.

2015-01-01

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd−/−) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd−/− mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd−/− mice. These changes were reduced in DiNOS, and compared with Sftpd−/− mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd−/−. Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces. PMID:26320150

Cerebrovasculoprotective Effects of Azilsartan Medoxomil in Diabetes

PubMed Central

Abdelsaid, Mohammed; Coucha, Maha; Ergul, Adviye

2014-01-01

We have shown that Goto-Kakizaki (GK) rats, a lean model of type 2 diabetes, develop significant cerebrovascular remodeling by 18 weeks of age, which is characterized by increased media thickness and matrix deposition. While early glycemic control prevents diabetes-mediated remodeling of the cerebrovasculature, whether the remodeling can be reversed is unknown. Given that angiotensin II Type 1 receptor blockers (ARBs) reverse pathological vascular remodeling and function independent of changes in blood pressure in other vascular beds, we hypothesized that azilsartan medoxomil, a new ARB, is vasculoprotective by preventing and reversing cerebrovascular remodeling in diabetes. Control Wistar and diabetic GK rats (n=6–8/group), were treated with vehicle (water) or azilsartan medoxomil (3 mg/kg/day) from 14 to 18 or 18 to 22 weeks of age before or after vascular remodeling is established, respectively. Blood glucose and blood pressure were monitored and middle cerebral artery structure and function were evaluated using pressurized arteriography. Blood glucose was higher in GK rats compared to Wistar rats. Azilsartan treatment lowered blood glucose in diabetes with no effect on blood pressure. Diabetic animals exhibited lower myogenic tone, increased wall thickness, and cross sectional area compared to controls, which were corrected by azilsartan treatment when started at the onset of diabetes or later after vascular remodeling is established. Azilsartan medoxomil offers preventive and therapeutic vasculoprotection in diabetes-induced cerebrovascular remodeling and myogenic dysfunction and this is independent of blood pressure. PMID:24999268

Perspectives on biomechanical growth and remodeling mechanisms in glaucoma⋆

PubMed Central

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

2012-01-01

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. PMID:23109748

Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling.

PubMed

Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K; Marmer, Barry; Goldberg, Gregory I; Neuman, Keir C

2016-07-26

Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal-strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments.

Increased Diels-Alderase activity through backbone remodeling guided by Foldit players.

PubMed

Eiben, Christopher B; Siegel, Justin B; Bale, Jacob B; Cooper, Seth; Khatib, Firas; Shen, Betty W; Players, Foldit; Stoddard, Barry L; Popovic, Zoran; Baker, David

2012-01-22

Computational enzyme design holds promise for the production of renewable fuels, drugs and chemicals. De novo enzyme design has generated catalysts for several reactions, but with lower catalytic efficiencies than naturally occurring enzymes. Here we report the use of game-driven crowdsourcing to enhance the activity of a computationally designed enzyme through the functional remodeling of its structure. Players of the online game Foldit were challenged to remodel the backbone of a computationally designed bimolecular Diels-Alderase to enable additional interactions with substrates. Several iterations of design and characterization generated a 24-residue helix-turn-helix motif, including a 13-residue insertion, that increased enzyme activity >18-fold. X-ray crystallography showed that the large insertion adopts a helix-turn-helix structure positioned as in the Foldit model. These results demonstrate that human creativity can extend beyond the macroscopic challenges encountered in everyday life to molecular-scale design problems.

Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling

PubMed Central

Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K.; Marmer, Barry; Goldberg, Gregory I.; Neuman, Keir C.

2016-01-01

Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal–strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments. PMID:27402741

Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

PubMed Central

Gomez, Juan F.; Cardona, Karen; Martinez, Laura; Saiz, Javier; Trenor, Beatriz

2014-01-01

Background 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. Objective In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations. Methods 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. Results 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. Conclusion 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. PMID:25054335

Size, shape, and stamina: the impact of left ventricular geometry on exercise capacity.

PubMed

Lam, Carolyn S P; Grewal, Jasmine; Borlaug, Barry A; Ommen, Steve R; Kane, Garvan C; McCully, Robert B; Pellikka, Patricia A

2010-05-01

Although several studies have examined the cardiac functional determinants of exercise capacity, few have investigated the effects of structural remodeling. The current study evaluated the association between cardiac geometry and exercise capacity. Subjects with ejection fraction > or = 50% and no valvular disease, myocardial ischemia, or arrhythmias were identified from a large prospective exercise echocardiography database. Left ventricular mass index and relative wall thickness were used to classify geometry into normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. All of the subjects underwent symptom-limited treadmill exercise according to standard Bruce protocol. Maximal exercise tolerance was measured in metabolic equivalents. Of 366 (60+/-14 years; 57% male) subjects, 166 (45%) had normal geometry, 106 (29%) had concentric remodeling, 40 (11%) had eccentric hypertrophy, and 54 (15%) had concentric hypertrophy. Geometry was related to exercise capacity: in descending order, the maximum achieved metabolic equivalents were 9.9+/-2.8 in normal, 8.9+/-2.6 in concentric remodeling, 8.6+/-3.1 in eccentric hypertrophy, and 8.0+/-2.7 in concentric hypertrophy (all P<0.02 versus normal). Left ventricular mass index and relative wall thickness were negatively correlated with exercise tolerance in metabolic equivalents (r=-0.14; P=0.009 and r=-0.21; P<0.001, respectively). Augmentation of heart rate and ejection fraction with exercise were blunted in concentric hypertrophy compared with normal, even after adjusting for medications. In conclusion, the pattern of ventricular remodeling is related to exercise capacity among low-risk adults. Subjects with concentric hypertrophy display the greatest limitation, and this is related to reduced systolic and chronotropic reserve. Reverse remodeling strategies may prevent or treat functional decline in patients with structural heart disease.

Size, Shape and Stamina: The Impact of Left Ventricular Geometry on Exercise Capacity

PubMed Central

Lam, Carolyn S.P.; Grewal, Jasmine; Borlaug, Barry A.; Ommen, Steve R.; Kane, Garvan C.; McCully, Robert B.; Pellikka, Patricia A.

2010-01-01

While several studies have examined the cardiac functional determinants of exercise capacity, few have investigated the effects of structural remodeling. The current study evaluated the association between cardiac geometry and exercise capacity. Subjects with ejection fraction ≥ 50% and no valvular disease, myocardial ischemia or arrhythmias were identified from a large prospective exercise echocardiography database. Left ventricular mass index and relative wall thickness were used to classify geometry into normal, concentric remodeling, eccentric hypertrophy and concentric hypertrophy. All subjects underwent symptom-limited treadmill exercise according to standard Bruce protocol. Maximal exercise tolerance was measured in metabolic equivalents. Of 366 (60±14 years; 57% male) subjects, 166(45%) had normal geometry, 106(29%) had concentric remodeling, 40(11%) had eccentric hypertrophy and 54(15%) had concentric hypertrophy. Geometry was related to exercise capacity: in descending order, the maximum achieved metabolic equivalents was 9.9±2.8 in normal, 8.9±2.6 in concentric remodeling, 8.6±3.1 in eccentric hypertrophy and 8.0±2.7 in concentric hypertrophy (all p<0.02 vs normal). Left ventricular mass index and relative wall thickness were negatively correlated with exercise tolerance in metabolic equivalents (r= -0.14; p=0.009 and r= -0.21; p<0.001, respectively). Augmentation of heart rate and ejection fraction with exercise were blunted in concentric hypertrophy compared to normal, even after adjusting for medications. In conclusion, the pattern of ventricular remodeling is related to exercise capacity among low-risk adults. Subjects with concentric hypertrophy display the greatest limitation and this is related to reduced systolic and chronotropic reserve. Reverse remodeling strategies may prevent or treat functional decline in patients with structural heart disease. PMID:20215563

Regulating the chromatin landscape: structural and mechanistic perspectives.

PubMed

Bartholomew, Blaine

2014-01-01

A large family of chromatin remodelers that noncovalently modify chromatin is crucial in cell development and differentiation. They are often the targets of cancer, neurological disorders, and other human diseases. These complexes alter nucleosome positioning, higher-order chromatin structure, and nuclear organization. They also assemble chromatin, exchange out histone variants, and disassemble chromatin at defined locations. We review aspects of the structural organization of these complexes, the functional properties of their protein domains, and variation between complexes. We also address the mechanistic details of these complexes in mobilizing nucleosomes and altering chromatin structure. A better understanding of these issues will be vital for further analyses of subunits of these chromatin remodelers, which are being identified as targets in human diseases by NGS (next-generation sequencing).

Wood used in residential repair and remodeling in the United States, 2014

Treesearch

Joe Elling; David B. McKeever

2018-01-01

The repair, remodeling, and renovation of existing residential structures and properties has been, and continues to be, a vital market for the use of wood products in the United States. This market is either the first or second largest market (alternating with new residential construction) for a number of wood products including softwood lumber, engineered wood...

Membrane Remodeling by the Double-Barrel Scaffolding Protein of Poxvirus

PubMed Central

Hijnen, Marcel; Schult, Philipp; Pettikiriarachchi, Anne; Mitra, Alok K.; Coulibaly, Fasséli

2011-01-01

In contrast to most enveloped viruses, poxviruses produce infectious particles that do not acquire their internal lipid membrane by budding through cellular compartments. Instead, poxvirus immature particles are generated from atypical crescent-shaped precursors whose architecture and composition remain contentious. Here we describe the 2.6 Å crystal structure of vaccinia virus D13, a key structural component of the outer scaffold of viral crescents. D13 folds into two jellyrolls decorated by a head domain of novel fold. It assembles into trimers that are homologous to the double-barrel capsid proteins of adenovirus and lipid-containing icosahedral viruses. We show that, when tethered onto artificial membranes, D13 forms a honeycomb lattice and assembly products structurally similar to the viral crescents and immature particles. The architecture of the D13 honeycomb lattice and the lipid-remodeling abilities of D13 support a model of assembly that exhibits similarities with the giant mimivirus. Overall, these findings establish that the first committed step of poxvirus morphogenesis utilizes an ancestral lipid-remodeling strategy common to icosahedral DNA viruses infecting all kingdoms of life. Furthermore, D13 is the target of rifampicin and its structure will aid the development of poxvirus assembly inhibitors. PMID:21931553

The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.

PubMed

Zhang, Y; LeRoy, G; Seelig, H P; Lane, W S; Reinberg, D

1998-10-16

Histone acetylation and deacetylation were found to be catalyzed by structurally distinct, multisubunit complexes that mediate, respectively, activation and repression of transcription. ATP-dependent nucleosome remodeling, mediated by different multisubunit complexes, was thought to be involved only in transcription activation. Here we report the isolation of a protein complex that contains both histone deacetylation and ATP-dependent nucleosome remodeling activities. The complex contains the histone deacetylases HDAC1/2, histone-binding proteins, the dermatomyositis-specific autoantigen Mi2beta, a polypeptide related to the metastasis-associated protein 1, and a novel polypeptide of 32 kDa. Patients with dermatomyositis have a high rate of malignancy. The finding that Mi2beta exists in a complex containing histone deacetylase and nucleosome remodeling activities suggests a role for chromatin reorganization in cancer metastasis.

Left ventricular remodelling in chronic primary mitral regurgitation: implications for medical therapy.

PubMed

McCutcheon, Keir; Manga, Pravin

Surgical repair or replacement of the mitral valve is currently the only recommended therapy for severe primary mitral regurgitation. The chronic elevation of wall stress caused by the resulting volume overload leads to structural remodelling of the muscular, vascular and extracellular matrix components of the myocardium. These changes are initially compensatory but in the long term have detrimental effects, which ultimately result in heart failure. Understanding the changes that occur in the myocardium due to volume overload at the molecular and cellular level may lead to medical interventions, which potentially could delay or prevent the adverse left ventricular remodelling associated with primary mitral regurgitation. The pathophysiological changes involved in left ventricular remodelling in response to chronic primary mitral regurgitation and the evidence for potential medical therapy, in particular beta-adrenergic blockers, are the focus of this review.

Non-Equilibrium Cytoquake Dynamics in Cytoskeletal Remodeling and Stabilization

PubMed Central

Alencar, Adriano Mesquita; Ferraz, Mariana Sacrini Ayres; Park, Chan Young; Millet, Emil; Trepat, Xavier; Butler, James P.; Fredberg, Jeffrey J.

2016-01-01

The cytoskeleton (CSK) is a tensed fiber framework that supports, shapes and stabilizes the cell. The CSK is in a constant state of remodeling, moreover, which is an active non-equilibrium thermodynamic process. We report here that cytoskeletal remodeling involves reconfigurations that are not only sudden but also are transmitted to great distances within the cell in a fashion reminiscent of quakes in the Earth's crust. Remarkably, these events in the cell conform both qualitatively and quantitatively to empirical laws typical of earthquakes, including hierarchical fault structures, cumulative energy distributions following the Gutenberg-Richter law, and rate of after-shocks following Omori's law. While it is well-established that remodeling and stabilization of the cytoskeleton are non-equilibrium process, these new unanticipated observations establish that these processes are also remarkably non-local and strongly cooperative. PMID:27722665

Hypertrophic remodeling of subcutaneous small resistance arteries in patients with Cushing's syndrome.

PubMed

Rizzoni, Damiano; Porteri, Enzo; De Ciuceis, Carolina; Rodella, Luigi F; Paiardi, Silvia; Rizzardi, Nicola; Platto, Caterina; Boari, Gianluca E M; Pilu, Annamaria; Tiberio, Guido A M; Giulini, Stefano M; Favero, Gaia; Rezzani, Rita; Rosei, Claudia Agabiti; Bulgari, Giuseppe; Avanzi, Daniele; Rosei, Enrico Agabiti

2009-12-01

Structural alterations of small resistance arteries in essential hypertensive patients (EH) are mostly characterized by inward eutrophic remodeling. However, we observed hypertrophic remodeling in patients with renovascular hypertension, in those with acromegaly, as well as in patients with non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure, even independent from the hemodynamic load. Cortisol may stimulate the renin-angiotensin system and may induce cardiac hypertrophy. However, presently no data are available about small artery structure in patients with Cushing's syndrome. We have investigated the structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12 EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries from sc fat were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media to lumen ratio, and the media cross-sectional area were measured, as well as indices of oxidative stress. Demographic variables were similar in the three groups, except for clinic blood pressure. The media to lumen ratio was significantly greater in EH and CS, compared with NT; no difference was observed between EH and CS. The media cross-sectional area was significantly greater in CS compared with EH and with NT. An increased vascular oxidative stress was present in CS, as demonstrated by increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric oxide synthase in the microvessels. Our results suggest the presence of hypertrophic remodeling in sc small resistance arteries of CS, probably as a consequence of growth-promoting properties of circulating cortisol and/or increased vascular oxidative stress.

Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

PubMed Central

Srinivasan, Vivek J.; Mandeville, Emiri T.; Can, Anil; Blasi, Francesco; Climov, Mihail; Daneshmand, Ali; Lee, Jeong Hyun; Yu, Esther; Radhakrishnan, Harsha; Lo, Eng H.; Sakadžić, Sava; Eikermann-Haerter, Katharina; Ayata, Cenk

2013-01-01

Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties. PMID:23940761

Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

NASA Astrophysics Data System (ADS)

Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

2004-04-01

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.

TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

DOE PAGES

Ye, Qiaozhen; Rosenberg, Scott C.; Moeller, Arne; ...

2015-04-28

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from amore » signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.« less

Cardiac Physiology of Aging: Extracellular Considerations.

PubMed

Horn, Margaux A

2015-07-01

Aging is a major risk factor for the development of cardiovascular disease, with the majority of affected patients being elderly. Progressive changes to myocardial structure and function occur with aging, often in concert with underlying pathologies. However, whether chronological aging results in a remodeled "aged substrate" has yet to be established. In addition to myocyte contractility, myocardial performance relies heavily on the cardiac extracellular matrix (ECM), the roles of which are as dynamic as they are significant; including providing structural integrity, assisting in force transmission throughout the cardiac cycle and acting as a signaling medium for communication between cells and the extracellular environment. In the healthy heart, ECM homeostasis must be maintained, and matrix deposition is in balance with degradation. Consequently, alterations to, or misregulation of the cardiac ECM has been shown to occur in both aging and in pathological remodeling with disease. Mounting evidence suggests that age-induced matrix remodeling may occur at the level of ECM control; including collagen synthesis, deposition, maturation, and degradation. Furthermore, experimental studies using aged animal models not only suggest that the aged heart may respond differently to insult than the young, but the identification of key players specific to remodeling with age may hold future therapeutic potential for the treatment of cardiac dysfunction in the elderly. This review will focus on the role of the cardiac interstitium in the physiology of the aging myocardium, with particular emphasis on the implications to age-related remodeling in disease. © 2015 American Physiological Society.

Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling

PubMed Central

Yamaguchi, Osamu; Higuchi, Yoshiharu; Hirotani, Shinichi; Kashiwase, Kazunori; Nakayama, Hiroyuki; Hikoso, Shungo; Takeda, Toshihiro; Watanabe, Tetsuya; Asahi, Michio; Taniike, Masayuki; Matsumura, Yasushi; Tsujimoto, Ikuko; Hongo, Kenichi; Kusakari, Yoichiro; Kurihara, Satoshi; Nishida, Kazuhiko; Ichijo, Hidenori; Hori, Masatsugu; Otsu, Kinya

2003-01-01

Left ventricular remodeling that occurs after myocardial infarction (MI) and pressure overload is generally accepted as a determinant of the clinical course of heart failure. The molecular mechanism of this process, however, remains to be elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We used ASK1 knockout mice (ASK-/-) to test the hypothesis that ASK1 is involved in development of left ventricular remodeling. ASK-/- hearts showed no morphological or histological defects. Echocardiography and cardiac catheterization revealed normal global structure and function. Left ventricular structural and functional remodeling were determined 4 weeks after coronary artery ligation or thoracic transverse aortic constriction (TAC). ASK-/- had significantly smaller increases in left ventricular end-diastolic and end-systolic ventricular dimensions and smaller decreases in fractional shortening in both experimental models compared with WT mice. The number of terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling-positive myocytes after MI or TAC was decreased in ASK-/- compared with that in WT mice. Overexpression of a constitutively active mutant of ASK1 induced apoptosis in isolated rat neonatal cardiomyocytes, whereas neonatal ASK-/- cardiomyocytes were resistant to H2O2-induced apoptosis. An in vitro kinase assay showed increased ASK1 activity in heart after MI or TAC in WT mice. Thus, ASK1 plays an important role in regulating left ventricular remodeling by promoting apoptosis. PMID:14665690

Prognostic heterogeneity of diastolic abnormalities along left ventricular remodeling continuum according to survival rates and laser polarimetry of blood

NASA Astrophysics Data System (ADS)

Boychuk, T. M.; Ivashchuk, O. I.; Kolomoiets, M. Y.; Mikhaliev, K. O.; Chursina, T. Y.

2011-09-01

The results of examination of 35 arterial hypertension and coronary heart disease patients are presented. The clinical, paraclinical and echocardiographic examinations were performed, and the parameters of prognosis (survival) according to Seattle Heart Failure Model, as well as the optical (polarimetric) properties of erythrocytic suspension were determined. The group of patients under examination was stratified by patterns of remodeling of left ventricle (LV). It was determined that increasing of anisotropy of erythrocytic suspension along LV remodeling patterns continuum correlates with aggravation of structural and functional state of LV and is associated with unfavorable prognosis.

Prognosis parameters and polarimetric properties of erythrocytes of the patients suffering from arterial hypertension and coronary heart disease at various patterns of left ventricular remodeling

NASA Astrophysics Data System (ADS)

Ivaschuk, Oleg I.; Kolomoiets, M. Y.; Mikhaliev, K. O.; Chursina, T. Ya.

2011-09-01

The results of examination of 35 arterial hypertension and coronary heart disease patients are presented. The clinical, paraclinical and echocardiographic examinations were performed, and the parameters of prognosis (survival) according to Seattle Heart Failure Model, as well as the optical (polarimetric) properties of erythrocytic suspension were determined. The group of patients under examination was stratified by patterns of remodeling of left ventricle (LV). It was determined that increasing of anisotropy of erythrocytic suspension along LV remodeling patterns continuum correlates with aggravation of structural and functional state of LV and is associated with unfavorable prognosis.

Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial Parasympathetic Remodeling through MAPKs/Neurturin Pathway.

PubMed

Liu, Lei; Geng, Jianqiang; Zhao, Hongwei; Yun, Fengxiang; Wang, Xiaoyu; Yan, Sen; Ding, Xue; Li, Wenpeng; Wang, Dingyu; Li, Jianqiang; Pan, Zhenwei; Gong, Yongtai; Tan, Xiangyang; Li, Yue

2015-01-01

Angiotensin II receptor blockers (ARBs) have been proved to be effective in preventing atrial structural and electrical remodelinq in atrial fibrillation (AF). Previous studies have shown that parasympathetic remodeling plays an important role in AF. However, the effects of ARBs on atrial parasympathetic remodeling in AF and the underlying mechanisms are still unknown. Canines were divided into sham-operated, pacing and valsartan + pacing groups. Rats and HL-1 cardiomyocytes were divided into control, angiotensin II (Ang II) and Ang II + valsartan groups, respectively. Atrial parasympathetic remodeling was quantified by immunocytochemical staining with anti-choline acetyltransferase (ChAT) antibody. Western blot was used to analysis the protein expression of neurturin. Both inducibility and duration were increased in chronic atrial rapid-pacing canine model, which was significantly inhibited by the treatment with valsartan. The density of ChAT-positive nerves and the protein level of neurturin in the atria of pacing canines were both increased than those in sham-operated canines. Ang II treatment not only induced atrial parasympathetic remodeling in rats, but also up-regulated the protein expression of neurturin. Valsartan significantly prevented atrial parasympathetic remodeling, and suppressed the protein expression of neurturin. Meanwhile, valsartan inhibited Ang II -induced up-regulation of neurturin and MAPKs in cultured cardiac myocytes. Inhibition of MAPKs dramatically attenuated neurturin up-regulation induced by Ang II. Parasympathetic remodeling was present in animals subjected to rapid pacing or Ang II infusion, which was mediated by MAPKs/neurturin pathway. Valsartan is able to prevent atrial parasympathetic remodeling and the occurrence of AF via inhibiting MAPKs/neurturin pathway. © 2015 S. Karger AG, Basel.

Cerebrovasculoprotective effects of azilsartan medoxomil in diabetes.

PubMed

Abdelsaid, Mohammed; Coucha, Maha; Ergul, Adviye

2014-11-01

We have shown that Goto-Kakizaki (GK) rats, a lean model of type 2 diabetes, develop significant cerebrovascular remodeling by the age of 18 weeks, which is characterized by increased media thickness and matrix deposition. Although early glycemic control prevents diabetes-mediated remodeling of the cerebrovasculature, whether the remodeling can be reversed is unknown. Given that angiotensin II type 1 receptor blockers reverse pathologic vascular remodeling and function independent of changes in blood pressure in other vascular beds, we hypothesized that azilsartan medoxomil, a new angiotensin II type 1 receptor blocker, is vasculoprotective by preventing and reversing cerebrovascular remodeling in diabetes. Control Wistar and diabetic GK rats (n = 6-8 per group) were treated with vehicle (water) or azilsartan medoxomil (3 mg/kg/d) from the age of 14 to 18 or 18 to 22 weeks before or after vascular remodeling is established, respectively. Blood glucose and blood pressure were monitored and middle cerebral artery structure and function were evaluated using pressurized arteriography. Blood glucose was higher in GK rats compared with Wistar rats. Azilsartan treatment lowered blood glucose in diabetic animals with no effect on blood pressure. Diabetic animals exhibited lower myogenic tone, increased wall thickness, and cross-sectional area compared with control group animals, which were corrected by azilsartan treatment when started at the onset of diabetes or later after vascular remodeling is established. Azilsartan medoxomil offers preventive and therapeutic vasculoprotection in diabetes-induced cerebrovascular remodeling and myogenic dysfunction and this is independent of blood pressure. Published by Elsevier Inc.

The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells.

PubMed

Xu, Bowen; Cai, Ling; Butler, Jason M; Chen, Dongliang; Lu, Xiongdong; Allison, David F; Lu, Rui; Rafii, Shahin; Parker, Joel S; Zheng, Deyou; Wang, Gang Greg

2018-03-13

Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia. Genome-wide transcriptome profiling revealed that BPTF loss caused downregulation of HSC-specific gene-expression programs, which contain several master transcription factors (Meis1, Pbx1, Mn1, and Lmo2) required for HSC maintenance and self-renewal. Furthermore, we show that BPTF potentiates the chromatin accessibility of key HSC "stemness" genes. These results demonstrate an essential requirement of the chromatin remodeler BPTF and NURF for activation of "stemness" gene-expression programs and proper function of adult HSCs. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

The Pivotal Role of Airway Smooth Muscle in Asthma Pathophysiology

PubMed Central

Ozier, Annaïg; Allard, Benoit; Bara, Imane; Girodet, Pierre-Olivier; Trian, Thomas; Marthan, Roger; Berger, Patrick

2011-01-01

Asthma is characterized by the association of airway hyperresponsiveness (AHR), inflammation, and remodelling. The aim of the present article is to review the pivotal role of airway smooth muscle (ASM) in the pathophysiology of asthma. ASM is the main effector of AHR. The mechanisms of AHR in asthma may involve a larger release of contractile mediators and/or a lower release of relaxant mediators, an improved ASM cell excitation/contraction coupling, and/or an alteration in the contraction/load coupling. Beyond its contractile function, ASM is also involved in bronchial inflammation and remodelling. Whereas ASM is a target of the inflammatory process, it can also display proinflammatory and immunomodulatory functions, through its synthetic properties and the expression of a wide range of cell surface molecules. ASM remodelling represents a key feature of asthmatic bronchial remodelling. ASM also plays a role in promoting complementary airway structural alterations, in particular by its synthetic function. PMID:22220184

Differential nuclear remodeling of mammalian somatic cells by Xenopus laevis oocyte and egg cytoplasm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alberio, Ramiro; Johnson, Andrew D.; Stick, Reimer

2005-07-01

The mechanisms governing nuclear reprogramming have not been fully elucidated yet; however, recent studies show a universally conserved ability of both oocyte and egg components to reprogram gene expression in somatic cells. The activation of genes associated with pluripotency by oocyte/egg components may require the remodeling of nuclear structures, such that they can acquire the features of early embryos and pluripotent cells. Here, we report on the remodeling of the nuclear lamina of mammalian cells by Xenopus oocyte and egg extracts. Lamin A/C is removed from somatic cells incubated in oocyte and egg extracts in an active process that requiresmore » permeable nuclear pores. Removal of lamin A/C is specific, since B-type lamins are not changed, and it is not dependent on the incorporation Xenopus egg specific lamin III. Moreover, transcriptional activity is differentially regulated in somatic cells incubated in the extracts. Pol I and II transcriptions are maintained in cells in oocyte extracts; however, both activities are abolished in egg extracts. Our study shows that components of oocyte and egg extracts can modify the nuclear lamina of somatic cells and that this nuclear remodeling induces a structural change in the nucleus which may have implications for transcriptional activity. These experiments suggest that modifications in the nuclear lamina structure by the removal of somatic proteins and the incorporation of oocyte/egg components may contribute to the reprogramming of somatic cell nuclei and may define a characteristic configuration of pluripotent cells.« less

Left ventricular remodeling in the post-infarction heart: a review of cellular, molecular mechanisms, and therapeutic modalities.

PubMed

Gajarsa, Jason J; Kloner, Robert A

2011-01-01

As more patients survive myocardial infarctions, the incidence of heart failure increases. After an infarction, the human heart undergoes a series of structural changes, which are governed by cellular and molecular mechanisms in a pathological metamorphosis termed "remodeling." This review will discuss the current developments in our understanding of these molecular and cellular events in remodeling and the various pharmacological, cellular and device therapies used to treat, and potentially retard, this condition. Specifically, this paper will examine the neurohormonal activity of the renin-angiotensin-aldosterone axis and its molecular effects on the heart. The emerging understanding of the extra-cellular matrix and the various active molecules within it, such as the matrix metalloproteinases, elicits new appreciation for their role in cardiac remodeling and as possible future therapeutic targets. Cell therapy with stem cells is another recent therapy with great potential in improving post-infarcted hearts. Lastly, the cellular and molecular effects of left ventricular assist devices on remodeling will be reviewed. Our increasing knowledge of the cellular and molecular mechanisms underlying cardiac remodeling enables us not only to better understand how our more successful therapies, like angiotensin-converting enzyme inhibitors, work, but also to explore new therapies of the future.

Coarse-Grained Models for Protein-Cell Membrane Interactions

PubMed Central

Bradley, Ryan; Radhakrishnan, Ravi

2015-01-01

The physiological properties of biological soft matter are the product of collective interactions, which span many time and length scales. Recent computational modeling efforts have helped illuminate experiments that characterize the ways in which proteins modulate membrane physics. Linking these models across time and length scales in a multiscale model explains how atomistic information propagates to larger scales. This paper reviews continuum modeling and coarse-grained molecular dynamics methods, which connect atomistic simulations and single-molecule experiments with the observed microscopic or mesoscale properties of soft-matter systems essential to our understanding of cells, particularly those involved in sculpting and remodeling cell membranes. PMID:26613047

Extracellular Matrix Remodeling: The Common Denominator in Connective Tissue DiseasesPossibilities for Evaluation and Current Understanding of the Matrix as More Than a Passive Architecture, but a Key Player in Tissue Failure

PubMed Central

Nielsen, Mette J.; Sand, Jannie M.; Henriksen, Kim; Genovese, Federica; Bay-Jensen, Anne-Christine; Smith, Victoria; Adamkewicz, Joanne I.; Christiansen, Claus; Leeming, Diana J.

2013-01-01

Abstract Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive tissue remodeling leading to tissue stiffness, as well as by changes in the signaling potential of both intact matrix and fragments thereof. Although tissue structure until recently was viewed as a simple architecture anchoring cells and proteins, this complex grid may contain essential information enabling the maintenance of the structure and normal functioning of tissue. The aims of this review are to (1) discuss the structural components of the matrix and the relevance of their mutations to the pathology of diseases such as fibrosis and cancer, (2) introduce the possibility that post-translational modifications (PTMs), such as protease cleavage, citrullination, cross-linking, nitrosylation, glycosylation, and isomerization, generated during pathology, may be unique, disease-specific biochemical markers, (3) list and review the range of simple enzyme-linked immunosorbent assays (ELISAs) that have been developed for assessing the extracellular matrix (ECM) and detecting abnormal ECM remodeling, and (4) discuss whether some PTMs are the cause or consequence of disease. New evidence clearly suggests that the ECM at some point in the pathogenesis becomes a driver of disease. These pathological modified ECM proteins may allow insights into complicated pathologies in which the end stage is excessive tissue remodeling, and provide unique and more pathology-specific biochemical markers. PMID:23046407

Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus.

PubMed

Gonçalves, N; Gomes-Ferreira, C; Moura, C; Roncon-Albuquerque, R; Leite-Moreira, A F; Falcão-Pires, I

2016-08-15

Diabetic cardiomyopathy is characterized by cardiac structural and functional abnormalities. Additionally, chronic pressure overload conditions are highly prevalent amongst diabetic population and this association leads to a more severe myocardial impairment. The differences in myocardial pathophysiology between type 1 and type 2 diabetes mellitus (DM) still remain to be clarified. Thus, we aimed to investigate biventricular structural and functional changes promoted by the two types of DM and the impact of concomitant chronic pressure overload. Wistar rats were injected with streptozotocin (Type 1 DM, T1DM) or fed with a hypercaloric diet (Type 2 DM, T2DM). Pressure overload was imposed in DM animals by aortic constriction and after 5weeks of DM the cardiac function and structure were evaluated. Both types of DM promoted hypertrophy, increased fibrosis and advanced glycation end-products deposition, in the two ventricles. Interestingly, the induced myocardial alterations were distinct. While T1DM stimulated a pronounced hypertrophy and extracellular matrix remodeling, T2DM induced functional impairment. The negative impact of the association of DM with aortic constriction was more pronounced in T2DM, promoting impaired function and increased stiffness, particularly in the right ventricle. Our study demonstrated that the two types of diabetes induce distinct cardiac alterations per se or when combined with chronic pressure overload. T1DM promoted a more extensive remodeling in cardiac structure while T2DM significantly impaired ventricular function. The impact of pressure overload was more notorious in T2DM as observed by worse myocardial remodeling, suggesting a higher susceptibility to the deleterious effects of chronic pressure overload, namely hypertension, among this diabetic population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Extensive vascular remodeling in the spinal cord of pre-symptomatic experimental autoimmune encephalomyelitis mice; increased vessel expression of fibronectin and the α5β1 integrin

PubMed Central

Boroujerdi, Amin; Welser-Alves, Jennifer V.; Milner, Richard

2013-01-01

Alterations in vascular structure and function are a central component of demyelinating disease. In addition to blood-brain barrier (BBB) breakdown, which occurs early in the course of disease, recent studies have described angiogenic remodeling, both in multiple sclerosis tissue and in the mouse demyelinating model, experimental autoimmune encephalomyelitis (EAE). As the precise timing of vascular remodeling in demyelinating disease has yet to be fully defined, the purpose of the current study was to define the time-course of these events in the MOG35-55 EAE model. Quantification of endothelial cell proliferation and vessel density revealed that a large part of angiogenic remodeling in cervical spinal cord white matter occurs during the pre-symptomatic phase of EAE. At the height of vascular remodeling, blood vessels in the cervical spinal cord showed strong transient upregulation of fibronectin and the α5β1 integrin. In vitro experiments revealed that α5 integrin inhibition reduced brain endothelial cell proliferation under inflammatory conditions. Interestingly, loss of vascular integrity was evident in all vessels during the first 4–7 days post-immunization, but after 14 days, was localized predominantly to venules. Taken together, our data demonstrate that extensive vascular remodeling occurs during the pre-symptomatic phase of EAE and point to a potential role for the fibronectin-α5β1 integrin interaction in promoting vascular remodeling during demyelinating disease. PMID:24056042

Extensive vascular remodeling in the spinal cord of pre-symptomatic experimental autoimmune encephalomyelitis mice; increased vessel expression of fibronectin and the α5β1 integrin.

PubMed

Boroujerdi, Amin; Welser-Alves, Jennifer V; Milner, Richard

2013-12-01

Alterations in vascular structure and function are a central component of demyelinating disease. In addition to blood-brain barrier (BBB) breakdown, which occurs early in the course of disease, recent studies have described angiogenic remodeling, both in multiple sclerosis tissue and in the mouse demyelinating model, experimental autoimmune encephalomyelitis (EAE). As the precise timing of vascular remodeling in demyelinating disease has yet to be fully defined, the purpose of the current study was to define the time-course of these events in the MOG35-55 EAE model. Quantification of endothelial cell proliferation and vessel density revealed that a large part of angiogenic remodeling in cervical spinal cord white matter occurs during the pre-symptomatic phase of EAE. At the height of vascular remodeling, blood vessels in the cervical spinal cord showed strong transient upregulation of fibronectin and the α5β1 integrin. In vitro experiments revealed that α5 integrin inhibition reduced brain endothelial cell proliferation under inflammatory conditions. Interestingly, loss of vascular integrity was evident in all vessels during the first 4-7days post-immunization, but after 14days, was localized predominantly to venules. Taken together, our data demonstrate that extensive vascular remodeling occurs during the pre-symptomatic phase of EAE and point to a potential role for the fibronectin-α5β1 integrin interaction in promoting vascular remodeling during demyelinating disease. © 2013.

Effect of ovariectomy and Sideritis euboea extract administration on large artery mechanics, morphology, and structure in middle-aged rats.

PubMed

Sokolis, Dimitrios P; Dimitriou, Constantinos A; Lelovas, Pavlos; Kostomitsopoulos, Nikolaos G; Dontas, Ismene A

2017-01-01

Arterial function is regulated by estrogen, but no consistent pattern of arterial mechanical remodeling in response to depleted estrogen levels is available. To examine long-term effects of ovariectomy (OVX) on the mechanical properties, morphology, and histological structure of the carotid artery in middle-aged rats and a potentially protective effect of Sideritis euboea extract (SID), commonly consumed as "mountain tea". 10-month-old female Wistar rats were allocated into control (sham-operated), OVX, OVX+SID, and OVX+MALT (maltodextrin; excipient used for dilution of SID) groups. They were sacrificed after 6 months and their carotid arteries were submitted to inflation/extension tests and to dimensional and histological evaluation. Remodeling in OVX rats was characterized by a decreased in situ axial extension ratio, along with increased opening angle, thickness, and area of the vessel wall and of its medial layer, but unchanged lumen diameter. Compositional changes involved increased elastin/collagen densities. Characterization by the "four-fiber" microstructure-motivated model revealed similar in situ biaxial response of carotid arteries in OVX and control rats. Carotid artery remodeling in OVX rats was largely consistent with hypertensive remodeling, despite the minor arterial pressure changes found, and was not altered by administration of SID, despite previous evidence of its osteo-protective effect.

Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Persson, Jenna; Ekwall, Karl, E-mail: karl.ekwall@ki.se; School of Life Sciences, University College Sodertorn, NOVUM, Huddinge

Eukaryotic DNA is packaged around octamers of histone proteins into nucleosomes, the basic unit of chromatin. In addition to enabling meters of DNA to fit within the confines of a nucleus, the structure of chromatin has functional implications for cell identity. Covalent chemical modifications to the DNA and to histones, histone variants, ATP-dependent chromatin remodelers, small noncoding RNAs and the level of chromatin compaction all contribute to chromosomal structure and to the activity or silencing of genes. These chromatin-level alterations are defined as epigenetic when they are heritable from mother to daughter cell. The great diversity of epigenomes that canmore » arise from a single genome permits a single, totipotent cell to generate the hundreds of distinct cell types found in humans. Two recent studies in mouse and in fly have highlighted the importance of Chd1 chromatin remodelers for maintaining an open, active chromatin state. Based on evidence from fission yeast as a model system, we speculate that Chd1 remodelers are involved in the disassembly of nucleosomes at promoter regions, thus promoting active transcription and open chromatin. It is likely that these nucleosomes are specifically marked for disassembly by the histone variant H2A.Z.« less

Hypertension and Atrial Fibrillation: An Intimate Association of Epidemiology, Pathophysiology, and Outcomes.

PubMed

Dzeshka, Mikhail S; Shahid, Farhan; Shantsila, Alena; Lip, Gregory Y H

2017-08-01

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia found in clinical practice. AF rarely exists as a single entity but rather as part of a diverse clinical spectrum of cardiovascular diseases, related to structural and electrical remodeling within the left atrium, leading to AF onset, perpetuation, and progression. Due to the high overall prevalence within the AF population arterial hypertension plays a significant role in the pathogenesis of AF and its complications. Fibroblast proliferation, apoptosis of cardiomyocytes, gap junction remodeling, accumulation of collagen both in atrial and ventricular myocardium all accompany ageing-related structural remodeling with impact on electrical activity. The presence of hypertension also stimulates oxidative stress, systemic inflammation, rennin-angiotensin-aldosterone and sympathetic activation, which further drives the remodeling process in AF. Importantly, both hypertension and AF independently increase the risk of cardiovascular and cerebrovascular events, e.g., stroke and myocardial infarction. Given that both AF and hypertension often present with limited on patient wellbeing, treatment may be delayed resulting in development of complications as the first clinical manifestation of the disease. Antithrombotic prevention in AF combined with strict blood pressure control is of primary importance, since stroke risk and bleeding risk are both greater with underlying hypertension. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The major architects of chromatin: architectural proteins in bacteria, archaea and eukaryotes.

PubMed

Luijsterburg, Martijn S; White, Malcolm F; van Driel, Roel; Dame, Remus Th

2008-01-01

The genomic DNA of all organisms across the three kingdoms of life needs to be compacted and functionally organized. Key players in these processes are DNA supercoiling, macromolecular crowding and architectural proteins that shape DNA by binding to it. The architectural proteins in bacteria, archaea and eukaryotes generally do not exhibit sequence or structural conservation especially across kingdoms. Instead, we propose that they are functionally conserved. Most of these proteins can be classified according to their architectural mode of action: bending, wrapping or bridging DNA. In order for DNA transactions to occur within a compact chromatin context, genome organization cannot be static. Indeed chromosomes are subject to a whole range of remodeling mechanisms. In this review, we discuss the role of (i) DNA supercoiling, (ii) macromolecular crowding and (iii) architectural proteins in genome organization, as well as (iv) mechanisms used to remodel chromosome structure and to modulate genomic activity. We conclude that the underlying mechanisms that shape and remodel genomes are remarkably similar among bacteria, archaea and eukaryotes.

Spine growth in the anterior cingulate cortex is necessary for the consolidation of contextual fear memory

PubMed Central

Vetere, Gisella; Restivo, Leonardo; Cole, Christina J.; Ross, P. Joel; Ammassari-Teule, Martine; Josselyn, Sheena A.; Frankland, Paul W.

2011-01-01

Remodeling of cortical connectivity is thought to allow initially hippocampus-dependent memories to be expressed independently of the hippocampus at remote time points. Consistent with this, consolidation of a contextual fear memory is associated with dendritic spine growth in neurons of the anterior cingulate cortex (aCC). To directly test whether such cortical structural remodeling is necessary for memory consolidation, we disrupted spine growth in the aCC at different times following contextual fear conditioning in mice. We took advantage of previous studies showing that the transcription factor myocyte enhancer factor 2 (MEF2) negatively regulates spinogenesis both in vitro and in vivo. We found that increasing MEF2-dependent transcription in the aCC during a critical posttraining window (but not at later time points) blocked both the consolidation-associated dendritic spine growth and subsequent memory expression. Together, these data strengthen the causal link between cortical structural remodeling and memory consolidation and, further, identify MEF2 as a key regulator of these processes. PMID:21531906

Time Course of Electrical Remodeling of Native Conduction After Cardiac Resynchronization Therapy and Its Impact on Clinical Outcome.

PubMed

Cvijić, Marta; Žižek, David; Antolič, Bor; Zupan, Igor

2017-03-01

Cardiac resynchronization therapy (CRT) induces structural and electrical remodeling (ER) in heart failure (HF) patients. Our aim was to assess time course of ER of native conduction and mechanical remodeling after CRT and impact of CRT-induced ER on clinical outcome. We prospectively included 62 patients (aged 66 ± 10 years). Echocardiographic and ECG parameters were measured at baseline and 1, 3, 6, 9, and 12 months after implantation. Biventricular pacing was temporary inhibited during each follow-up to record intrinsic ECG. ER was defined as a decrease in native pre-implantation QRS duration ≥10 ms. During follow-up HF hospitalizations, cardiovascular death and transplantation (combined end point) were recorded. There were significant changes in intrinsic ECG parameters during follow-up; the narrowing of QRS duration was already observed after 1 month (median 185 ms [interquartile range (IQR) 175-194] vs 180 ms [170-194]; P < .001). Left ventricular (LV) volumes decreased only after 3 months of CRT (median end-systolic volume 167 mL [137-206] vs 140 mL [112-196]; P < .001). Only patients with ER (n = 24) exhibited significant mechanical remodeling and showed superior survival free from the combined end point compared with patients without ER (log-rank P = .028). Electrical remodeling of native conduction precedes detectable left ventricular structural changes after CRT. ER of native conduction is associated with better clinical outcome following CRT. Copyright © 2016 Elsevier Inc. All rights reserved.

Mars Life? - Microscopic Tubular Structures

NASA Image and Video Library

1996-08-09

This electron microscope image shows extremely tiny tubular structures that are possible microscopic fossils of bacteria-like organisms that may have lived on Mars more than 3.6 billion years ago. http://photojournal.jpl.nasa.gov/catalog/PIA00285

Mars Life? - Microscopic Egg-shaped Structures

NASA Image and Video Library

1996-08-09

This electron microscope image shows egg-shaped structures, some of which may be possible microscopic fossils of Martian origin as discussed by NASA research published in the Aug. 16, 1996. http://photojournal.jpl.nasa.gov/catalog/PIA00286

High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure

PubMed Central

Rosa-Garrido, Manuel; Chapski, Douglas J.; Schmitt, Anthony D.; Kimball, Todd H.; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J.; Ren, Shuxun; Wang, Yibin; Ren, Bing

2017-01-01

Background: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. Methods: To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload–induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Results: Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. Conclusions: These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. PMID:28802249

High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure.

PubMed

Rosa-Garrido, Manuel; Chapski, Douglas J; Schmitt, Anthony D; Kimball, Todd H; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J; Ren, Shuxun; Wang, Yibin; Ren, Bing; Vondriska, Thomas M

2017-10-24

Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. © 2017 The Authors.

Spatio-temporal regulation of connexin43 phosphorylation and gap junction dynamics.

PubMed

Solan, Joell L; Lampe, Paul D

2018-01-01

Gap junctions are specialized membrane domains containing tens to thousands of intercellular channels. These channels permit exchange of small molecules (<1000Da) including ions, amino acids, nucleotides, metabolites and secondary messengers (e.g., calcium, glucose, cAMP, cGMP, IP 3 ) between cells. The common reductionist view of these structures is that they are composed entirely of integral membrane proteins encoded by the 21 member connexin human gene family. However, it is clear that the normal physiological function of this structure requires interaction and regulation by a variety of proteins, especially kinases. Phosphorylation is capable of directly modulating connexin channel function but the most dramatic effects on gap junction activity occur via the organization of the gap junction structures themselves. This is a direct result of the short half-life of the primary gap junction protein, connexin, which requires them to be constantly assembled, remodeled and turned over. The biological consequences of this remodeling are well illustrated during cardiac ischemia, a process wherein gap junctions are disassembled and remodeled resulting in arrhythmia and ultimately heart failure. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomechanical remodeling of obstructed guinea pig jejunum

PubMed Central

Zhao, Jingbo; Liao, Donghua; Yang, Jian; Gregersen, Hans

2010-01-01

Data on morphological and biomechanical remodeling are needed to understand the mechanisms behind intestinal obstruction. The effect of partial obstruction on mechanical properties with reference to the zero-stress state and on the histomorphological properties of the guinea pig small intestine was determined in this study. Partial obstruction and sham operation were surgically created in mid-jejunum of guinea pigs. The animals survived 2, 4, 7, and 14 days respectively. The age-matched guinea pigs that were not operated served as normal controls. The segment proximal to the obstruction site was used for histological analysis, no-load state and zero-stress state data, and distension test. The segment for distension was immersed in an organ bath and inflated to 10 cmH20. The outer diameter change during the inflation was monitored using a microscope with CCD camera. Circumferential stresses and strains were computed from the diameter, pressure and the zero-stress state data. The opening angle and absolute value of residual strain decreased (P<0.01 and P<0.001) whereas the wall thickness, wall cross-sectional area, and the wall stiffness increased after 7 days obstruction (P<0.05, P<0.01). Histologically, the muscle and submucosa layers, especially the circumferential muscle layer increased in thickness after obstruction. The opening angle and residual strain mainly depended on the thickness of the muscle layer whereas the wall stiffness mainly depended on the thickness of the submucosa layer. In conclusion, the histomorphological and biomechanical properties of small intestine (referenced for the first time to the zero-stress state) remodel proximal to the obstruction site in a time-dependent manner. PMID:20189575

Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria

PubMed Central

Colman, Michael A; Aslanidi, Oleg V; Kharche, Sanjay; Boyett, Mark R; Garratt, Clifford; Hancox, Jules C; Zhang, Henggui

2013-01-01

Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche–Ramirez–Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca2+ handling. The single cell models for control and AF-remodelled conditions were incorporated into multicellular three-dimensional (3D) atrial tissue models. Effects of the AF-induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re-entry. The dynamic behaviour of re-entrant excitation waves in the 3D models was characterised. In our simulations, AF-induced electrical remodelling abbreviated atrial APD non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re-entry initiation at these tissue junctions was increased. The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. Under the AF-remodelled condition, re-entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF-induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate initiation and maintenance of re-entrant excitation waves. PMID:23732649

Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria.

PubMed

Colman, Michael A; Aslanidi, Oleg V; Kharche, Sanjay; Boyett, Mark R; Garratt, Clifford; Hancox, Jules C; Zhang, Henggui

2013-09-01

Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche-Ramirez-Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca(2+) handling. The single cell models for control and AF-remodelled conditions were incorporated into multicellular three-dimensional (3D) atrial tissue models. Effects of the AF-induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re-entry. The dynamic behaviour of re-entrant excitation waves in the 3D models was characterised. In our simulations, AF-induced electrical remodelling abbreviated atrial APD non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re-entry initiation at these tissue junctions was increased. The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. Under the AF-remodelled condition, re-entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF-induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate initiation and maintenance of re-entrant excitation waves.

Effects of estradiol on learned helplessness and associated remodeling of hippocampal spine synapses in female rats.

PubMed

Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; Maclusky, Neil J; Leranth, Csaba; Duman, Ronald S

2010-01-15

Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in female subjects is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant desipramine. Considering that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life might influence behavioral and synaptic responses to stress and depression. With electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n = 70), under different conditions of estradiol exposure. Stress induced an acute and persistent loss of hippocampal spine synapses, whereas subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either before stress or before escape testing of nonstressed animals increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. These findings suggest that hippocampal spine synapse remodeling might be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression.

Zone-specific remodeling of tumor blood vessels affects tumor growth.

PubMed

Tilki, Derya; Kilic, Nerbil; Sevinc, Sema; Zywietz, Friedrich; Stief, Christian G; Ergun, Suleyman

2007-11-15

Chaotic organization, abnormal leakiness, and structural instability are characteristics of tumor vessels. However, morphologic events of vascular remodeling in relation to tumor growth are not sufficiently studied yet. By using the rat rhabdomyosarcoma tumor model vascular morphogenesis was studied by light and electron microscopy and immunohistochemistry in relation to tumor regions such as tumor surrounding (TSZ), marginal (TMZ), intermediate (TIZ), and center (TCZ) zones. The analyses revealed that blood vessels of TSZ display a regular ultrastructure, whereas blood vessels of TMZ showed a chaotic organization and unstable structure with a diffuse or even lacking basal lamina, and missing or irregular assembled periendothelial cells. In contrast, blood vessels of TIZ and TCZ exhibited a more or less stabilized vessel structure with increased diameter. Correspondingly, normal assembly of alpha-smooth-muscle-actin (alpha-SMA)-positive cells into the vessel wall was observed in blood vessels of TSZ, TIZ, and TCZ. Also, Ang1 immunostaining was strongest in large vessels of TIZ and TCZ, whereas Ang2 staining was prominent in small vessels of TIZ. Tie2 staining was detectable in small and large vessels of all tumor zones. Immunostaining for alpha(v)beta(3)-integrin was strongest in small vessels of TMZ, whereas large vessels of TIZ and TCZ were almost negative. The results indicate a zone-specific remodeling of tumor blood vessels by stabilization of vessels in TIZ and TCZ, whereas small vessels of these zones obviously undergo regression leading to tumor necrosis. Thus, a better understanding of vascular remodeling and stabilization in tumors would enable new strategies in tumor therapy and imaging. (c) 2007 American Cancer Society.

A model for one-dimensional morphoelasticity and its application to fibroblast-populated collagen lattices.

PubMed

Menon, Shakti N; Hall, Cameron L; McCue, Scott W; McElwain, D L Sean

2017-10-01

The mechanical behaviour of solid biological tissues has long been described using models based on classical continuum mechanics. However, the classical continuum theories of elasticity and viscoelasticity cannot easily capture the continual remodelling and associated structural changes in biological tissues. Furthermore, models drawn from plasticity theory are difficult to apply and interpret in this context, where there is no equivalent of a yield stress or flow rule. In this work, we describe a novel one-dimensional mathematical model of tissue remodelling based on the multiplicative decomposition of the deformation gradient. We express the mechanical effects of remodelling as an evolution equation for the effective strain, a measure of the difference between the current state and a hypothetical mechanically relaxed state of the tissue. This morphoelastic model combines the simplicity and interpretability of classical viscoelastic models with the versatility of plasticity theory. A novel feature of our model is that while most models describe growth as a continuous quantity, here we begin with discrete cells and develop a continuum representation of lattice remodelling based on an appropriate limit of the behaviour of discrete cells. To demonstrate the utility of our approach, we use this framework to capture qualitative aspects of the continual remodelling observed in fibroblast-populated collagen lattices, in particular its contraction and its subsequent sudden re-expansion when remodelling is interrupted.

Clinical Nonlinear Laser Imaging of Human Skin: A Review

PubMed Central

Pavone, Francesco Saverio

2014-01-01

Nonlinear optical microscopy has the potential of being used in vivo as a noninvasive imaging modality for both epidermal and dermal imaging. This paper reviews the capabilities of nonlinear microscopy as a noninvasive high-resolution tool for clinical skin inspection. In particular, we show that two-photon fluorescence microscopy can be used as a diagnostic tool for characterizing epidermal layers by means of a morphological examination. Additional functional information on the metabolic state of cells can be provided by measuring the fluorescence decay of NADH. This approach allows differentiating epidermal layers having different structural and cytological features and has the potential of diagnosing pathologies in a very early stage. Regarding therapy follow-up, we demonstrate that nonlinear microscopy could be successfully used for monitoring the effect of a treatment. In particular, combined two-photon fluorescence and second-harmonic generation microscopy were used in vivo for monitoring collagen remodeling after microablative fractional laser resurfacing and for quantitatively monitoring psoriasis on the basis of the morphology of epidermal cells and dermal papillae. We believe that the described microscopic modalities could find in the near future a stable place in a clinical dermatological setting for quantitative diagnostic purposes and as a monitoring method for various treatments. PMID:25250337

Illuminating the Mechanistic Roles of Enzyme Conformational Dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, Jeffrey A.; Dunderstadt, Karl; Watkins, Lucas P.

2007-11-13

Many enzymes mold their structures to enclose substrates in their active sites such that conformational remodeling may be required during each catalytic cycle. In adenylate kinase (AK), this involves a large-amplitude rearrangement of the enzyme’s lid domain. Using our method of high-resolution single-molecule FRET, we directly followed AK’s domain movements on its catalytic time scale. To quantitatively measure the enzyme’s entire conformational distribution, we have applied maximum entropy-based methods to remove photon-counting noise from single-molecule data. This analysis shows unambiguously that AK is capable of dynamically sampling two distinct states, which correlate well with those observed by x-ray crystallography. Unexpectedly,more » the equilibrium favors the closed, active-site-forming configurations even in the absence of substrates. Our experiments further showed that interaction with substrates, rather than locking the enzyme into a compact state, restricts the spatial extent of conformational fluctuations and shifts the enzyme’s conformational equilibrium toward the closed form by increasing the closing rate of the lid. Integrating these microscopic dynamics into macroscopic kinetics allows us to model lid opening-coupled product release as the enzyme’s rate-limiting step.« less

Translational Genomics: Practical Applications of the Genomic Revolution in Breast Cancer.

PubMed

Yates, Lucy R; Desmedt, Christine

2017-06-01

The genomic revolution has fundamentally changed our perception of breast cancer. It is now apparent from DNA-based massively parallel sequencing data that at the genomic level, every breast cancer is unique and shaped by the mutational processes to which it was exposed during its lifetime. More than 90 breast cancer driver genes have been identified as recurrently mutated, and many occur at low frequency across the breast cancer population. Certain cancer genes are associated with traditionally defined histologic subtypes, but genomic intertumoral heterogeneity exists even between cancers that appear the same under the microscope. Most breast cancers contain subclonal populations, many of which harbor driver alterations, and subclonal structure is typically remodeled over time, across metastasis and as a consequence of treatment interventions. Genomics is deepening our understanding of breast cancer biology, contributing to an accelerated phase of targeted drug development and providing insights into resistance mechanisms. Genomics is also providing tools necessary to deliver personalized cancer medicine, but a number of challenges must still be addressed. Clin Cancer Res; 23(11); 2630-9. ©2017 AACR See all articles in this CCR Focus section, "Breast Cancer Research: From Base Pairs to Populations." ©2017 American Association for Cancer Research.

Cellular and molecular basis of RV hypertrophy in congenital heart disease

PubMed Central

Iacobazzi, D; Suleiman, M-S; Ghorbel, M; George, SJ; Caputo, M; Tulloh, RM

2016-01-01

RV hypertrophy (RVH) is one of the triggers of RV failure in congenital heart disease (CHD). Therefore, improving our understanding of the cellular and molecular basis of this pathology will help in developing strategic therapeutic interventions to enhance patient benefit in the future. This review describes the potential mechanisms that underlie the transition from RVH to RV failure. In particular, it addresses structural and functional remodelling that encompass contractile dysfunction, metabolic changes, shifts in gene expression and extracellular matrix remodelling. Both ischaemic stress and reactive oxygen species production are implicated in triggering these changes and will be discussed. Finally, RV remodelling in response to various CHDs as well as the potential role of biomarkers will be addressed. PMID:26516182

Stepwise Loop Insertion Strategy for Active Site Remodeling to Generate Novel Enzyme Functions.

PubMed

Hoque, Md Anarul; Zhang, Yong; Chen, Liuqing; Yang, Guangyu; Khatun, Mst Afroza; Chen, Haifeng; Hao, Liu; Feng, Yan

2017-05-19

The remodeling of active sites to generate novel biocatalysts is an attractive and challenging task. We developed a stepwise loop insertion strategy (StLois), in which randomized residue pairs are inserted into active site loops. The phosphotriesterase-like lactonase from Geobacillus kaustophilus (GkaP-PLL) was used to investigate StLois's potential for changing enzyme function. By inserting six residues into active site loop 7, the best variant ML7-B6 demonstrated a 16-fold further increase in catalytic efficiency toward ethyl-paraoxon compared with its initial template, that is a 609-fold higher, >10 7 fold substrate specificity shift relative to that of wild-type lactonase. The remodeled variants displayed 760-fold greater organophosphate hydrolysis activity toward the organophosphates parathion, diazinon, and chlorpyrifos. Structure and docking computations support the source of notably inverted enzyme specificity. Considering the fundamental importance of active site loops, the strategy has potential for the rapid generation of novel enzyme functions by loop remodeling.

Local alignment vectors reveal cancer cell-induced ECM fiber remodeling dynamics

PubMed Central

Lee, Byoungkoo; Konen, Jessica; Wilkinson, Scott; Marcus, Adam I.; Jiang, Yi

2017-01-01

Invasive cancer cells interact with the surrounding extracellular matrix (ECM), remodeling ECM fiber network structure by condensing, degrading, and aligning these fibers. We developed a novel local alignment vector analysis method to quantitatively measure collagen fiber alignment as a vector field using Circular Statistics. This method was applied to human non-small cell lung carcinoma (NSCLC) cell lines, embedded as spheroids in a collagen gel. Collagen remodeling was monitored using second harmonic generation imaging under normal conditions and when the LKB1-MARK1 pathway was disrupted through RNAi-based approaches. The results showed that inhibiting LKB1 or MARK1 in NSCLC increases the collagen fiber alignment and captures outward alignment vectors from the tumor spheroid, corresponding to high invasiveness of LKB1 mutant cancer cells. With time-lapse imaging of ECM micro-fiber morphology, the local alignment vector can measure the dynamic signature of invasive cancer cell activity and cell-migration-induced ECM and collagen remodeling and realigning dynamics. PMID:28045069

Cardiac Metabolism in Heart Failure - Implications beyond ATP production

PubMed Central

Doenst, Torsten; Nguyen, T. Dung; Abel, E. Dale

2013-01-01

The heart has a high rate of ATP production and turnover which is required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure revealed several metabolic alterations termed metabolic remodeling, ranging from changes in substrate utilization to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during heart failure. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to heart failure by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in heart failure not only results in impaired cardiac energetics, but also induces other processes implicated in the development of heart failure such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in heart failure may have significant therapeutic relevance that goes beyond the energetic aspect. PMID:23989714

Adjusting protein graphs based on graph entropy.

PubMed

Peng, Sheng-Lung; Tsay, Yu-Wei

2014-01-01

Measuring protein structural similarity attempts to establish a relationship of equivalence between polymer structures based on their conformations. In several recent studies, researchers have explored protein-graph remodeling, instead of looking a minimum superimposition for pairwise proteins. When graphs are used to represent structured objects, the problem of measuring object similarity become one of computing the similarity between graphs. Graph theory provides an alternative perspective as well as efficiency. Once a protein graph has been created, its structural stability must be verified. Therefore, a criterion is needed to determine if a protein graph can be used for structural comparison. In this paper, we propose a measurement for protein graph remodeling based on graph entropy. We extend the concept of graph entropy to determine whether a graph is suitable for representing a protein. The experimental results suggest that when applied, graph entropy helps a conformational on protein graph modeling. Furthermore, it indirectly contributes to protein structural comparison if a protein graph is solid.

Adjusting protein graphs based on graph entropy

PubMed Central

2014-01-01

Measuring protein structural similarity attempts to establish a relationship of equivalence between polymer structures based on their conformations. In several recent studies, researchers have explored protein-graph remodeling, instead of looking a minimum superimposition for pairwise proteins. When graphs are used to represent structured objects, the problem of measuring object similarity become one of computing the similarity between graphs. Graph theory provides an alternative perspective as well as efficiency. Once a protein graph has been created, its structural stability must be verified. Therefore, a criterion is needed to determine if a protein graph can be used for structural comparison. In this paper, we propose a measurement for protein graph remodeling based on graph entropy. We extend the concept of graph entropy to determine whether a graph is suitable for representing a protein. The experimental results suggest that when applied, graph entropy helps a conformational on protein graph modeling. Furthermore, it indirectly contributes to protein structural comparison if a protein graph is solid. PMID:25474347

Thoracic and abdominal aortas stiffen through unique extracellular matrix changes in intrauterine growth restricted fetal sheep.

PubMed

Dodson, R Blair; Rozance, Paul J; Petrash, Carson C; Hunter, Kendall S; Ferguson, Virginia L

2014-02-01

Intrauterine growth restriction (IUGR) is a fetal complication of pregnancy epidemiologically linked to cardiovascular disease in the newborn later in life. However, the mechanism is poorly understood with very little research on the vascular structure and function during development in healthy and IUGR neonates. Previously, we found vascular remodeling and increased stiffness in the carotid and umbilical arteries, but here we examine the remodeling and biomechanics in the larger vessels more proximal to the heart. To study this question, thoracic and abdominal aortas were collected from a sheep model of placental insufficiency IUGR (PI-IUGR) due to exposure to elevated ambient temperatures. Aortas from control (n = 12) and PI-IUGR fetuses (n = 10) were analyzed for functional biomechanics and structural remodeling. PI-IUGR aortas had a significant increase in stiffness (P < 0.05), increased collagen content (P < 0.05), and decreased sulfated glycosaminoglycan content (P < 0.05). Our derived constitutive model from experimental data related increased stiffness to reorganization changes of increased alignment angle of collagen fibers and increased elastin (P < 0.05) in the thoracic aorta and increased concentration of collagen fibers in the abdominal aorta toward the circumferential direction verified through use of histological techniques. This fetal vascular remodeling in PI-IUGR may set the stage for possible altered growth and development and help to explain the pathophysiology of adult cardiovascular disease in previously IUGR individuals.

A new purified Lawsoniaside remodels amyloid-β42 fibrillation into a less toxic and non-amyloidogenic pathway.

PubMed

Dhouafli, Zohra; Leri, Manuela; Bucciantini, Monica; Stefani, Massimo; Gadhoumi, Hamza; Mahjoub, Borhane; Ben Jannet, Hichem; Guillard, Jérôme; Tounsi, Moufida Saidani; Ksouri, Riadh; Hayouni, El Akrem

2018-07-15

Mounting evidence indicates soluble Aβ 42 oligomers as the most toxic species causing neuronal death which leads to the onset and progression of Alzheimer disease (AD). Recently, it has been found that neurotoxic Aβ 42 oligomers grow from monomeric species or arise following secondary nucleation by preformed mature fibrils. Thus, the use of natural compounds such as polyphenols to hinder the growth or to remodel Aβ 42 fibrils is one of the most promising strategies for AD treatment. In our previous study, we showed that 1, 2, 4-trihydroxynaphthalene-2-O-β-d-glucopyranoside (THNG) inhibits Aβ 42 aggregation during the early steps of the aggregation process, inhibits its conformational change to a β-sheet-rich structure, decreases its polymerization, inhibits its fibrillogenisis and reduces oxidative stress and aggregate cytotoxicity. Here, we used different spectroscopic and cell culture methods to check the effect of THNG on fibrils disaggregation. We showed that THNG binds to mature Aβ 42 fibrils, rearrange their secondary structure, and remodels them into non-amyloid, less toxic, species by inhibiting their interaction with the plasma membrane. Our findings reveal that THNG is a good agent to remodel amyloid fibrils and could be used as a starting molecular scaffold to design new anti-AD drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

40 CFR 35.6015 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., repair, remodeling, improvement, or extension of buildings, structures or other property. Contract. A... 300. Operable unit. A discrete action, as described in the Cooperative Agreement or Superfund State...). Real property. Land, including land improvements, structures, and appurtenances thereto, excluding...

40 CFR 35.6015 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., repair, remodeling, improvement, or extension of buildings, structures or other property. Contract. A... 300. Operable unit. A discrete action, as described in the Cooperative Agreement or Superfund State...). Real property. Land, including land improvements, structures, and appurtenances thereto, excluding...

RNA helicase proteins as chaperones and remodelers

PubMed Central

Jarmoskaite, Inga; Russell, Rick

2014-01-01

Superfamily 2 helicase proteins are ubiquitous in RNA biology and have an extraordinarily broad set of functional roles. Central among these roles are to promote rearrangements of structured RNAs and to remodel RNA-protein complexes (RNPs), allowing formation of native RNA structure or progression through a functional cycle of structures. While all superfamily 2 helicases share a conserved helicase core, they are divided evolutionarily into several families, and it is principally proteins from three families, the DEAD-box, DEAH/RHA and Ski2-like families, that function to manipulate structured RNAs and RNPs. Strikingly, there are emerging differences in the mechanisms of these proteins, both between families and within the largest family (DEAD-box), and these differences appear to be tuned to their RNA or RNP substrates and their specific roles. This review outlines basic mechanistic features of the three families and surveys individual proteins and the current understanding of their biological substrates and mechanisms. PMID:24635478

Kinases and chromatin structure

PubMed Central

Miotto, Benoit

2013-01-01

Chromatin structure is regulated by families of proteins that are able to covalently modify the histones and the DNA, as well as to regulate the spacing of nucleosomes along the DNA. Over the years, these chromatin remodeling factors have been proven to be essential to a variety of processes, including gene expression, DNA replication, and chromosome cohesion. The function of these remodeling factors is regulated by a number of chemical and developmental signals and, in turn, changes in the chromatin structure eventually contribute to the response to changes in the cellular environment. Exciting new research findings by the laboratories of Sharon Dent and Steve Jackson indicate, in two different contexts, that changes in the chromatin structure may, in reverse, signal to intracellular signaling pathways to regulate cell fate. The discoveries clearly challenge our traditional view of ‘epigenetics’, and may have important implications in human health. PMID:23917692

Particle Interactions Mediated by Dynamical Networks: Assessment of Macroscopic Descriptions

NASA Astrophysics Data System (ADS)

Barré, J.; Carrillo, J. A.; Degond, P.; Peurichard, D.; Zatorska, E.

2018-02-01

We provide a numerical study of the macroscopic model of Barré et al. (Multiscale Model Simul, 2017, to appear) derived from an agent-based model for a system of particles interacting through a dynamical network of links. Assuming that the network remodeling process is very fast, the macroscopic model takes the form of a single aggregation-diffusion equation for the density of particles. The theoretical study of the macroscopic model gives precise criteria for the phase transitions of the steady states, and in the one-dimensional case, we show numerically that the stationary solutions of the microscopic model undergo the same phase transitions and bifurcation types as the macroscopic model. In the two-dimensional case, we show that the numerical simulations of the macroscopic model are in excellent agreement with the predicted theoretical values. This study provides a partial validation of the formal derivation of the macroscopic model from a microscopic formulation and shows that the former is a consistent approximation of an underlying particle dynamics, making it a powerful tool for the modeling of dynamical networks at a large scale.

Particle Interactions Mediated by Dynamical Networks: Assessment of Macroscopic Descriptions.

PubMed

Barré, J; Carrillo, J A; Degond, P; Peurichard, D; Zatorska, E

2018-01-01

We provide a numerical study of the macroscopic model of Barré et al. (Multiscale Model Simul, 2017, to appear) derived from an agent-based model for a system of particles interacting through a dynamical network of links. Assuming that the network remodeling process is very fast, the macroscopic model takes the form of a single aggregation-diffusion equation for the density of particles. The theoretical study of the macroscopic model gives precise criteria for the phase transitions of the steady states, and in the one-dimensional case, we show numerically that the stationary solutions of the microscopic model undergo the same phase transitions and bifurcation types as the macroscopic model. In the two-dimensional case, we show that the numerical simulations of the macroscopic model are in excellent agreement with the predicted theoretical values. This study provides a partial validation of the formal derivation of the macroscopic model from a microscopic formulation and shows that the former is a consistent approximation of an underlying particle dynamics, making it a powerful tool for the modeling of dynamical networks at a large scale.

Large area fabrication of plasmonic nanoparticle grating structure by conventional scanning electron microscope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sudheer,, E-mail: sudheer@rrcat.gov.in; Tiwari, P.; Rai, V. N.

Plasmonic nanoparticle grating (PNG) structure of different periods has been fabricated by electron beam lithography using silver halide based transmission electron microscope film as a substrate. Conventional scanning electron microscope is used as a fabrication tool for electron beam lithography. Optical microscope and energy dispersive spectroscopy (EDS) have been used for its morphological and elemental characterization. Optical characterization is performed by UV-Vis absorption spectroscopic technique.

Mars Life? - Microscopic Structures

NASA Image and Video Library

1996-08-09

In the center of this electron microscope image of a small chip from a meteorite are several tiny structures that are possible microscopic fossils of primitive, bacteria-like organisms that may have lived on Mars more than 3.6 billion years ago. http://photojournal.jpl.nasa.gov/catalog/PIA00283

Shear Stress Induced Reorganization of the Keratin Intermediate Filament Network Requires Phosphorylation by Protein Kinase C ζ

PubMed Central

Sivaramakrishnan, Sivaraj; Schneider, Jaime L.; Sitikov, Albert; Goldman, Robert D.

2009-01-01

Keratin intermediate filaments (KIFs) form a fibrous polymer network that helps epithelial cells withstand external mechanical forces. Recently, we established a correlation between the structure of the KIF network and its local mechanical properties in alveolar epithelial cells. Shear stress applied across the cell surface resulted in the structural remodeling of KIF and a substantial increase in the elastic modulus of the network. This study examines the mechanosignaling that regulates the structural remodeling of the KIF network. We report that the shear stress–mediated remodeling of the KIF network is facilitated by a twofold increase in the dynamic exchange rate of KIF subunits, which is regulated in a PKC ζ and 14-3-3–dependent manner. PKC ζ phosphorylates K18pSer33, and this is required for the structural reorganization because the KIF network in A549 cells transfected with a dominant negative PKC ζ, or expressing the K18Ser33Ala mutation, is unchanged. Blocking the shear stress–mediated reorganization results in reduced cellular viability and increased apoptotic levels. These data suggest that shear stress mediates the phosphorylation of K18pSer33, which is required for the reorganization of the KIF network, resulting in changes in mechanical properties of the cell that help maintain the integrity of alveolar epithelial cells. PMID:19357195

Mars Life? - Microscopic Tubular Structures

NASA Technical Reports Server (NTRS)

1996-01-01

This electron microscope image shows extremely tiny tubular structures that are possible microscopic fossils of bacteria-like organisms that may have lived on Mars more than 3.6 billion years ago. A two-year investigation by a NASA research team found organic molecules, mineral features characteristic of biological activity and possible microscopic fossils such as these inside of an ancient Martian rock that fell to Earth as a meteorite. The largest possible fossils are less than 1/100th the diameter of a human hair in size while most are ten times smaller. The fossil-like structures were found in carbonate minerals formed along pre-existing fractures in the meteorite in a fashion similar to the way fossils occur in limestone on Earth, although on a microscopic scale.

Embryonic multipotent progenitors remodel the Drosophila airways during metamorphosis

PubMed Central

Pitsouli, Chrysoula; Perrimon, Norbert

2010-01-01

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. PMID:20940225

Adaptive optical microscope for brain imaging in vivo

NASA Astrophysics Data System (ADS)

Wang, Kai

2017-04-01

The optical heterogeneity of biological tissue imposes a major limitation to acquire detailed structural and functional information deep in the biological specimens using conventional microscopes. To restore optimal imaging performance, we developed an adaptive optical microscope based on direct wavefront sensing technique. This microscope can reliably measure and correct biological samples induced aberration. We demonstrated its performance and application in structural and functional brain imaging in various animal models, including fruit fly, zebrafish and mouse.

Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation.

PubMed

Stembridge, Mike; Ainslie, Philip N; Hughes, Michael G; Stöhr, Eric J; Cotter, James D; Nio, Amanda Q X; Shave, Rob

2014-08-01

Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. Copyright © 2014 the American Physiological Society.

Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation

PubMed Central

Ainslie, Philip N.; Hughes, Michael G.; Stöhr, Eric J.; Cotter, James D.; Nio, Amanda Q. X.; Shave, Rob

2014-01-01

Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. PMID:24876358

The Chromatin Remodeler Isw1 Prevents CAG Repeat Expansions During Transcription in Saccharomyces cerevisiae

PubMed Central

Koch, Melissa R.; House, Nealia C. M.; Cosetta, Casey M.; Jong, Robyn M.; Salomon, Christelle G.; Joyce, Cailin E.; Philips, Elliot A.; Su, Xiaofeng A.; Freudenreich, Catherine H.

2018-01-01

CAG/CTG trinucleotide repeats are unstable sequences that are difficult to replicate, repair, and transcribe due to their structure-forming nature. CAG repeats strongly position nucleosomes; however, little is known about the chromatin remodeling needed to prevent repeat instability. In a Saccharomyces cerevisiae model system with CAG repeats carried on a YAC, we discovered that the chromatin remodeler Isw1 is required to prevent CAG repeat expansions during transcription. CAG repeat expansions in the absence of Isw1 were dependent on both transcription-coupled repair (TCR) and base-excision repair (BER). Furthermore, isw1∆ mutants are sensitive to methyl methanesulfonate (MMS) and exhibit synergistic MMS sensitivity when combined with BER or TCR pathway mutants. We conclude that CAG expansions in the isw1∆ mutant occur during a transcription-coupled excision repair process that involves both TCR and BER pathways. We observed increased RNA polymerase II (RNAPII) occupancy at the CAG repeat when transcription of the repeat was induced, but RNAPII binding did not change in isw1∆ mutants, ruling out a role for Isw1 remodeling in RNAPII progression. However, nucleosome occupancy over a transcribed CAG tract was altered in isw1∆ mutants. Based on the known role of Isw1 in the reestablishment of nucleosomal spacing after transcription, we suggest that a defect in this function allows DNA structures to form within repetitive DNA tracts, resulting in inappropriate excision repair and repeat-length changes. These results establish a new function for Isw1 in directly maintaining the chromatin structure at the CAG repeat, thereby limiting expansions that can occur during transcription-coupled excision repair. PMID:29305386

A Bioreactor to Identify the Driving Mechanical Stimuli of Tissue Growth and Remodeling.

PubMed

van Kelle, Mathieu A J; Oomen, Pim J A; Bulsink, Jurgen A; Janssen-van den Broek, Marloes W J T; Lopata, Richard G P; Rutten, Marcel C M; Loerakker, Sandra; Bouten, Carlijn V C

2017-06-01

Tissue growth and remodeling are essential processes that should ensure long-term functionality of tissue-engineered (TE) constructs. Even though it is widely recognized that these processes strongly depend on mechanical stimuli, the underlying mechanisms of mechanically induced growth and remodeling are only partially understood. It is generally accepted that cells sense mechanical changes and respond by altering their surroundings, by means of extracellular matrix growth and remodeling, in an attempt to return to a certain preferred mechanical homeostatic state. However, the exact mechanical cues that trigger cells to synthesize and remodel their environment remain unclear. To identify the driving mechanical stimuli of these processes, it is critical to be able to temporarily follow the mechanical state of developing tissues under physiological loading conditions. Therefore, a novel "versatile tissue growth and remodeling" (Vertigro) bioreactor was developed that is capable of tissue culture and mechanical stimulation for a prolonged time period, while simultaneously performing mechanical testing. The Vertigro's unique two-chamber design allows easy, sterile handling of circular 3D TE constructs in a dedicated culture chamber, while a separate pressure chamber facilitates a pressure-driven dynamic loading regime during culture. As a proof-of-concept, temporal changes in the mechanical state of cultured tissues were quantified using nondestructive mechanical testing by means of a classical bulge test, in which the tissue displacement was tracked using ultrasound imaging. To demonstrate the successful development of the bioreactor system, compositional, structural, and geometrical changes were qualitatively and quantitatively assessed using a series of standard analysis techniques. With this bioreactor and associated mechanical analysis technique, a powerful toolbox has been developed to quantitatively study and identify the driving mechanical stimuli of engineered tissue growth and remodeling.

The cell wall of Arabidopsis thaliana influences actin network dynamics.

PubMed

Tolmie, Frances; Poulet, Axel; McKenna, Joseph; Sassmann, Stefan; Graumann, Katja; Deeks, Michael; Runions, John

2017-07-20

In plant cells, molecular connections link the cell wall-plasma membrane-actin cytoskeleton to form a continuum. It is hypothesized that the cell wall provides stable anchor points around which the actin cytoskeleton remodels. Here we use live cell imaging of fluorescently labelled marker proteins to quantify the organization and dynamics of the actin cytoskeleton and to determine the impact of disrupting connections within the continuum. Labelling of the actin cytoskeleton with green fluorescent protein (GFP)-fimbrin actin-binding domain 2 (FABD2) resulted in a network composed of fine filaments and thicker bundles that appeared as a highly dynamic remodelling meshwork. This differed substantially from the GFP-Lifeact-labelled network that appeared much more sparse with thick bundles that underwent 'simple movement', in which the bundles slightly change position, but in such a manner that the structure of the network was not substantially altered during the time of observation. Label-dependent differences in actin network morphology and remodelling necessitated development of two new image analysis techniques. The first of these, 'pairwise image subtraction', was applied to measurement of the more rapidly remodelling actin network labelled with GFP-FABD2, while the second, 'cumulative fluorescence intensity', was used to measure bulk remodelling of the actin cytoskeleton when labelled with GFP-Lifeact. In each case, these analysis techniques show that the actin cytoskeleton has a decreased rate of bulk remodelling when the cell wall-plasma membrane-actin continuum is disrupted either by plasmolysis or with isoxaben, a drug that specifically inhibits cellulose deposition. Changes in the rate of actin remodelling also affect its functionality, as observed by alteration in Golgi body motility. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats.

PubMed

Frisbee, Jefferson C

2003-07-01

Whereas previous studies have demonstrated that the development of syndrome X in obese Zucker rats (OZR) is associated with impaired arteriolar reactivity to vasoactive stimuli, additional results from these studies indicate that the passive diameter of skeletal muscle arterioles is reduced in OZR versus lean Zucker rats (LZR). On the basis of these prior observations, the present study evaluated structural alterations to the skeletal muscle microcirculation as potential contributors to an elevated vascular resistance. Isolated skeletal muscle resistance arterioles exhibited a reduced passive diameter at all levels of intralumenal pressure and a left-shifted stress-strain curve in OZR versus LZR, indicative of structural remodeling of individual arterioles. Histological analyses using Griffonia simplicifolia I lectin-stained sections of skeletal muscle demonstrated reduced microvessel density (rarefaction) in OZR versus LZR, suggesting remodeling of entire microvascular networks. Finally, under maximally dilated conditions, constant flow-perfused skeletal muscle of OZR exhibited significant elevations in perfusion pressure versus LZR, indicative of an increased resistance to perfusion within the microcirculation. These data suggest that developing structural alterations to the skeletal muscle microcirculation in OZR result in elevated vascular resistance, which may, acting in concert with impaired arteriolar reactivity, contribute to blunted active hyperemic responses and compromised performance of in situ skeletal muscle with elevated metabolic demand.

Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity

NASA Technical Reports Server (NTRS)

Delp, M. D.; Colleran, P. N.; Wilkerson, M. K.; McCurdy, M. R.; Muller-Delp, J.

2000-01-01

Hindlimb unloading of rats results in a diminished ability of skeletal muscle arterioles to constrict in vitro and elevate vascular resistance in vivo. The purpose of the present study was to determine whether alterations in the mechanical environment (i.e., reduced fluid pressure and blood flow) of the vasculature in hindlimb skeletal muscles from 2-wk hindlimb-unloaded (HU) rats induces a structural remodeling of arterial microvessels that may account for these observations. Transverse cross sections were used to determine media cross-sectional area (CSA), wall thickness, outer perimeter, number of media nuclei, and vessel luminal diameter of feed arteries and first-order (1A) arterioles from soleus and the superficial portion of gastrocnemius muscles. Endothelium-dependent dilation (ACh) was also determined. Media CSA of resistance arteries was diminished by hindlimb unloading as a result of decreased media thickness (gastrocnemius muscle) or reduced vessel diameter (soleus muscle). ACh-induced dilation was diminished by 2 wk of hindlimb unloading in soleus 1A arterioles, but not in gastrocnemius 1A arterioles. These results indicate that structural remodeling and functional adaptations of the arterial microvasculature occur in skeletal muscles of the HU rat; the data suggest that these alterations may be induced by reductions in transmural pressure (gastrocnemius muscle) and wall shear stress (soleus muscle).

Extracellular matrix hydrogels from decellularized tissues: Structure and function.

PubMed

Saldin, Lindsey T; Cramer, Madeline C; Velankar, Sachin S; White, Lisa J; Badylak, Stephen F

2017-02-01

Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed. More than 70 papers have been published on extracellular matrix (ECM) hydrogels created from source tissue in almost every organ system. The present manuscript represents a review of ECM hydrogels and attempts to identify structure-function relationships that influence the tissue remodeling outcomes and gaps in the understanding thereof. There is a Phase 1 clinical trial now in progress for an ECM hydrogel. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Lymph node biophysical remodeling is associated with melanoma lymphatic drainage

PubMed Central

Rohner, Nathan Andrew; McClain, Jacob; Tuell, Sara Lydia; Warner, Alex; Smith, Blair; Yun, Youngho; Mohan, Abhinav; Sushnitha, Manuela; Thomas, Susan Napier

2015-01-01

Tissue remodeling is a characteristic of many solid tumor malignancies including melanoma. By virtue of tumor lymphatic transport, remodeling pathways active within the local tumor microenvironment have the potential to be operational within lymph nodes (LNs) draining the tumor interstitium. Here, we show that lymphatic drainage from murine B16 melanomas in syngeneic, immune-competent C57Bl/6 mice is associated with LN enlargement as well as nonuniform increases in bulk tissue elasticity and viscoelasticity, as measured by the response of whole LNs to compression. These remodeling responses, which quickly manifest in tumor-draining lymph nodes (TDLNs) after tumor inoculation and before apparent metastasis, were accompanied by changes in matrix composition, including up to 3-fold increases in the abundance of soluble collagen and hyaluronic acid. Intranodal pressures were also significantly increased in TDLNs (+1 cmH2O) relative to both non-tumor-draining LNs (−1 cmH2O) and LNs from naive animals (−1 to 2 cmH2O). These data suggest that the reorganization of matrix structure, composition, and fluid microenvironment within LNs associated with tumor lymphatic drainage parallels remodeling seen in primary malignancies and has the potential to regulate the adhesion, proliferation, and signaling function of LN-resident cells involved in directing melanoma disease progression.—Rohner, N. A., McClain, J., Tuell, S. L., Warner, A., Smith, B., Yun, Y., Mohan, A., Sushnitha, M., Thomas, S. N. Lymph node biophysical remodeling is associated with melanoma lymphatic drainage. PMID:26178165

Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease.

PubMed

Royce, Simon G; Dang, William; Ververis, Katherine; De Sampayo, Nishika; El-Osta, Assam; Tang, Mimi L K; Karagiannis, Tom C

2011-12-01

Airway remodeling and airway hyperresponsiveness are major aspects of asthma pathology that are not targeted optimally by existing anti-inflammatory drugs. Histone deacetylase inhibitors have a wide range of effects that may potentially abrogate aspects of remodeling. One such histone deacetylase inhibitor is valproic acid (2-propylvaleric acid). Valproic acid is used clinically as an anti-epileptic drug and is a potent inhibitor of class I histone deacetylases but also inhibits class II histone deacetylases. We used valproic acid as a molecular model of histone deacetylase inhibition in vivo in chronic allergic airways disease mice with airway remodeling and airway hyperresponsiveness. Wild-type Balb/c mice with allergic airways disease were treated with valproic acid or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and examination of lung tissue sections. Remodeling was assessed by morphometric analysis of histochemically stained slides and lung function was assessed by invasive plethysmography measurement of airway resistance. Valproic acid treatment did not affect inflammation parameters; however, valproic acid treatment resulted in reduced epithelial thickness as compared to vehicle treated mice (p < 0.01), reduced subepithelial collagen deposition (p < 0.05) and attenuated airway hyperresponsiveness (p < 0.05 and p < 0.01 for the two highest doses of methacholine, respectively). These findings show that treatment with valproic acid can reduce structural airway remodeling changes and hyperresponsiveness, providing further evidence for the potential use of histone deacetylase inhibitors for the treatment of asthma.

Automated 4D analysis of dendritic spine morphology: applications to stimulus-induced spine remodeling and pharmacological rescue in a disease model

PubMed Central

2011-01-01

Uncovering the mechanisms that regulate dendritic spine morphology has been limited, in part, by the lack of efficient and unbiased methods for analyzing spines. Here, we describe an automated 3D spine morphometry method and its application to spine remodeling in live neurons and spine abnormalities in a disease model. We anticipate that this approach will advance studies of synapse structure and function in brain development, plasticity, and disease. PMID:21982080

Performance evaluation on cool roofs for green remodeling

NASA Astrophysics Data System (ADS)

Yun, Yosun; Cho, Dongwoo; Cho, Kyungjoo

2018-06-01

Cool roofs refer that maximize heat emission, and minimize the absorption of solar radiation energy, by applying high solar reflectance paints, or materials to roofs or rooftops. The application of cool roofs to existing buildings does not need to take structural issues into consideration, as rooftop greening, is an alternative that can be applied to existing buildings easily. This study installed a cool roofs on existing buildings, and evaluated the performances, using the results to propose certification standards for green remodeling, considering the cool roof-related standards.

Mars Life? - Microscopic Tubular Structures

NASA Image and Video Library

1996-08-09

This electron microscope image shows tubular structures of likely Martian origin. These structures are very similar in size and shape to extremely tiny microfossils found in some Earth rocks. http://photojournal.jpl.nasa.gov/catalog/PIA00287

The solid state environment orchestrates embryonic development and tissue remodeling

NASA Technical Reports Server (NTRS)

Damsky, C. H.; Moursi, A.; Zhou, Y.; Fisher, S. J.; Globus, R. K.

1997-01-01

Cell interactions with extracellular matrix and with other cells play critical roles in morphogenesis during development and in tissue homeostasis and remodeling throughout life. Extracellular matrix is information-rich, not only because it is comprised of multifunctional structural ligands for cell surface adhesion receptors, but also because it contains peptide signaling factors, and proteinases and their inhibitors. The functions of these groups of molecules are extensively interrelated. In this review, three primary cell culture models are described that focus on adhesion receptors and their roles in complex aspects of morphogenesis and remodeling: the regulation of proteinase expression by fibronectin and integrins in synovial fibroblasts; the regulation of osteoblast differentiation and survival by fibronectin, and the regulation of trophoblast differentiation and invasion by integrins, cadherins and immunoglobulin family adhesion receptors.

Seasonal and post-trauma remodeling in cone-dominant ground squirrel retina

PubMed Central

Merriman, Dana K.; Sajdak, Benjamin S.; Li, Wei; Jones, Bryan W.

2016-01-01

With a photoreceptor mosaic containing ~85% cones, the ground squirrel is one of the richest known mammalian sources of these important retinal cells. It also has a visual ecology much like the human’s. While the ground squirrel retina is understandably prominent in the cone biochemistry, physiology, and circuitry literature, far less is known about the remodeling potential of its retinal pigment epithelium, neurons, macroglia, or microglia. This review aims to summarize the data from ground squirrel retina to this point in time, and to relate them to data from other brain areas where appropriate. We begin with a survey of the ground squirrel visual system, making comparisons with traditional rodent models and with human. Because this animal’s status as a hibernator often goes unnoticed in the vision literature, we then present a brief primer on hibernation biology. Next we review what is known about ground squirrel retinal remodeling concurrent with deep torpor and with rapid recovery upon re-warming. Notable here is rapidly-reversible, temperature-dependent structural plasticity of cone ribbon synapses, as well as pre- and post-synaptic plasticity throughout diverse brain regions. It is not yet clear if retinal cell types other than cones engage in torpor-associated synaptic remodeling. We end with the small but intriguing literature on the ground squirrel retina’s remodeling responses to insult by retinal detachment. Notable for widespread loss of (cone) photoreceptors, there is surprisingly little remodeling of the RPE or Müller cells. Microglial activation appears minimal, and remodeling of surviving second- and third-order neurons seems absent, but both require further study. In contrast, traumatic brain injury in the ground squirrel elicits typical macroglial and microglial responses. Overall, the data to date strongly suggest a heretofore unrecognized, natural checkpoint between retinal deafferentiation and RPE and Müller cell remodeling events. As we continue to discover them, the unique ways by which ground squirrel retina responds to hibernation or injury may be adaptable to therapeutic use. PMID:26808487

Minimizing Interpolation Bias and Precision Error in In Vivo μCT-based Measurements of Bone Structure and Dynamics

PubMed Central

de Bakker, Chantal M. J.; Altman, Allison R.; Li, Connie; Tribble, Mary Beth; Lott, Carina; Tseng, Wei-Ju; Liu, X. Sherry

2016-01-01

In vivo μCT imaging allows for high-resolution, longitudinal evaluation of bone properties. Based on this technology, several recent studies have developed in vivo dynamic bone histomorphometry techniques that utilize registered μCT images to identify regions of bone formation and resorption, allowing for longitudinal assessment of bone remodeling. However, this analysis requires a direct voxel-by-voxel subtraction between image pairs, necessitating rotation of the images into the same coordinate system, which introduces interpolation errors. We developed a novel image transformation scheme, matched-angle transformation (MAT), whereby the interpolation errors are minimized by equally rotating both the follow-up and baseline images instead of the standard of rotating one image while the other remains fixed. This new method greatly reduced interpolation biases caused by the standard transformation. Additionally, our study evaluated the reproducibility and precision of bone remodeling measurements made via in vivo dynamic bone histomorphometry. Although bone remodeling measurements showed moderate baseline noise, precision was adequate to measure physiologically relevant changes in bone remodeling, and measurements had relatively good reproducibility, with intra-class correlation coefficients of 0.75-0.95. This indicates that, when used in conjunction with MAT, in vivo dynamic histomorphometry provides a reliable assessment of bone remodeling. PMID:26786342

Minimizing Interpolation Bias and Precision Error in In Vivo µCT-Based Measurements of Bone Structure and Dynamics.

PubMed

de Bakker, Chantal M J; Altman, Allison R; Li, Connie; Tribble, Mary Beth; Lott, Carina; Tseng, Wei-Ju; Liu, X Sherry

2016-08-01

In vivo µCT imaging allows for high-resolution, longitudinal evaluation of bone properties. Based on this technology, several recent studies have developed in vivo dynamic bone histomorphometry techniques that utilize registered µCT images to identify regions of bone formation and resorption, allowing for longitudinal assessment of bone remodeling. However, this analysis requires a direct voxel-by-voxel subtraction between image pairs, necessitating rotation of the images into the same coordinate system, which introduces interpolation errors. We developed a novel image transformation scheme, matched-angle transformation (MAT), whereby the interpolation errors are minimized by equally rotating both the follow-up and baseline images instead of the standard of rotating one image while the other remains fixed. This new method greatly reduced interpolation biases caused by the standard transformation. Additionally, our study evaluated the reproducibility and precision of bone remodeling measurements made via in vivo dynamic bone histomorphometry. Although bone remodeling measurements showed moderate baseline noise, precision was adequate to measure physiologically relevant changes in bone remodeling, and measurements had relatively good reproducibility, with intra-class correlation coefficients of 0.75-0.95. This indicates that, when used in conjunction with MAT, in vivo dynamic histomorphometry provides a reliable assessment of bone remodeling.

Delayed Exercise Promotes Remodeling in Sub-Rupture Fatigue Damaged Tendons

PubMed Central

Bell, R.; Boniello, M.R.; Gendron, N.R.; Flatow, E.L.; Andarawis-Puri, N.

2015-01-01

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. PMID:25732052

Quantification of Protein-Induced Membrane Remodeling Kinetics In Vitro with Lipid Multilayer Gratings

PubMed Central

Lowry, Troy W.; Hariri, Hanaa; Prommapan, Plengchart; Kusi-Appiah, Aubrey; Vafai, Nicholas; Bienkiewicz, Ewa A.; Van Winkle, David H.; Stagg, Scott M.

2016-01-01

The dynamic self-organization of lipids in biological systems is a highly regulated process that enables the compartmentalization of living systems at micro- and nanoscopic scales. Consequently, quantitative methods for assaying the kinetics of supramolecular remodeling such as vesicle formation from planar lipid bilayers or multilayers are needed to understand cellular self-organization. Here, a new nanotechnology-based method for quantitative measurements of lipid–protein interactions is presented and its suitability for quantifying the membrane binding, inflation, and budding activity of the membrane-remodeling protein Sar1 is demonstrated. Lipid multilayer gratings are printed onto surfaces using nanointaglio and exposed to Sar1, resulting in the inflation of lipid multilayers into unilamellar structures, which can be observed in a label-free manner by monitoring the diffracted light. Local variations in lipid multilayer volume on the surface is used to vary substrate availability in a microarray format. A quantitative model is developed that allows quantification of binding affinity (KD) and kinetics (kon and koff). Importantly, this assay is uniquely capable of quantifying membrane remodeling. Upon Sar1-induced inflation of single bilayers from surface supported multilayers, the semicylindrical grating lines are observed to remodel into semispherical buds when a critical radius of curvature is reached. PMID:26649649

Bitter taste receptor agonists alter mitochondrial function and induce autophagy in airway smooth muscle cells.

PubMed

Pan, Shi; Sharma, Pawan; Shah, Sushrut D; Deshpande, Deepak A

2017-07-01

Airway remodeling, including increased airway smooth muscle (ASM) mass, is a hallmark feature of asthma and COPD. We previously identified the expression of bitter taste receptors (TAS2Rs) on human ASM cells and demonstrated that known TAS2R agonists could promote ASM relaxation and bronchodilation and inhibit mitogen-induced ASM growth. In this study, we explored cellular mechanisms mediating the antimitogenic effect of TAS2R agonists on human ASM cells. Pretreatment of ASM cells with TAS2R agonists chloroquine and quinine resulted in inhibition of cell survival, which was largely reversed by bafilomycin A1, an autophagy inhibitor. Transmission electron microscope studies demonstrated the presence of double-membrane autophagosomes and deformed mitochondria. In ASM cells, TAS2R agonists decreased mitochondrial membrane potential and increased mitochondrial ROS and mitochondrial fragmentation. Inhibiting dynamin-like protein 1 (DLP1) reversed TAS2R agonist-induced mitochondrial membrane potential change and attenuated mitochondrial fragmentation and cell death. Furthermore, the expression of mitochondrial protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) and mitochondrial localization of DLP1 were significantly upregulated by TAS2R agonists. More importantly, inhibiting Bnip3 mitochondrial localization by dominant-negative Bnip3 significantly attenuated cell death induced by TAS2R agonist. Collectively the TAS2R agonists chloroquine and quinine modulate mitochondrial structure and function, resulting in ASM cell death. Furthermore, Bnip3 plays a central role in TAS2R agonist-induced ASM functional changes via a mitochondrial pathway. These findings further establish the cellular mechanisms of antimitogenic effects of TAS2R agonists and identify a novel class of receptors and pathways that can be targeted to mitigate airway remodeling as well as bronchoconstriction in obstructive airway diseases. Copyright © 2017 the American Physiological Society.

Optical second harmonic images of 90 deg domain structure in BaTiO3 and periodically inverted antiparallel domains in LiTaO3

NASA Astrophysics Data System (ADS)

Uesu, Y.; Kurimura, S.; Yamamoto, Y.

1995-04-01

Applied is a microscope to observations of 90 deg ferroelectric domain structure in BaTiO3 and inverted periodically are ferroelectric domains in LiTaO3. It is founded that the second harmonic generation microscope gives information which cannot be obtained by ordinary optical microscopes. The developed nonlinear optical microscope builds two dimensional second harmonic image of a specimen with inhomogenous distribution of d(sub ijk) and applied the microscope to observations of inhomogeneity in some nonlinear-optical organic microcrystals.

The BioStent: novel concept for a viable stent structure.

PubMed

Weinandy, Stefan; Rongen, Lisanne; Schreiber, Fabian; Cornelissen, Christian; Flanagan, Thomas Cormac; Mahnken, Andreas; Gries, Thomas; Schmitz-Rode, Thomas; Jockenhoevel, Stefan

2012-09-01

Percutaneous stenting of occluded peripheral vessels is a well-established technique in clinical practice. Unfortunately, the patency rates of small-caliber vessels after stenting remain unsatisfactory. The aim of the BioStent concept is to overcome in-stent restenosis by excluding the diseased vessel segment entirely from the blood stream, in addition to providing an intact endothelial cell layer. The concept combines the principles of vascular tissue engineering with a self-expanding stent: casting of the stent within a cellularized fibrin gel structure, followed by bioreactor conditioning, allows complete integration of the stent within engineered tissue. Small-caliber BioStents (Ø=6 mm; n=4) were produced by casting a nitinol stent within a thin fibrin/vascular smooth muscle cell (vSMC) mixture, followed by luminal endothelial cell seeding, and conditioning of the BioStent within a bioreactor system. The potential remodeling of the fibrin component into tissue was analyzed using routine histological methods. Scanning electron microscopy was used to assess the luminal endothelial cell coverage following the conditioning phase and crimping of the stent. The BioStent was shown to be noncytotoxic, with no significant effect on cell proliferation. Gross and microscopic analysis revealed complete integration of the nitinol component within a viable tissue structure. Hematoxylin and eosin staining revealed a homogenous distribution of vSMCs throughout the thickness of the BioStent, while a smooth, confluent luminal endothelial cell lining was evident and not significantly affected by the crimping/release process. The BioStent concept is a platform technology offering a novel opportunity to generate a viable, self-expanding stent structure with a functional endothelial cell lining. This platform technology can be transferred to different applications depending on the luminal cell lining required.

Do mandibular cross-sectional properties and dental microwear give similar dietary signals?

PubMed

Organ, Jason M; Ruff, Christopher B; Teaford, Mark F; Nisbett, Richard A

2006-08-01

Previous animal experimental work evaluating the effects of dietary consistency on mastication was generally limited to studies of either mandibular structure or rates and types of tooth wear. Control groups fed hard diets (HD) consistently exhibited increased cortical remodeling and/or bone strength when compared to groups fed soft diets (SD). Results of tooth-wear studies showed faster rates of tooth wear in HD animals. This study evaluates the effects of dietary differences on both mandibular structural morphology and postcanine dental microwear in the same animals. We examined mandibles and dentitions from eight miniature swine, raised from 4 weeks to 9 months of age on HD and SD (n = 4, each group). Mandibular structural properties were calculated from peripheral quantitative computed tomography slices at the dp3-dp4 and dp4-M1 junctions. Dental microwear analysis was performed on mandibular lingual crushing facets of dp4 and M1, using photomicrographs of high-resolution casts taken at 500x magnification in a scanning electron microscope. Our results suggest that between the dp3-dp4 contact, HD animals have mandibles that are stronger and more rigid mediolaterally than SD animals. At the dp4-M1 contact, HD animals have mandibles that are stronger and more rigid mediolaterally, dorsoventrally, and in torsion than SD animals. Dental microwear results indicate that SD pigs have higher incidences of pitting and more overall microwear features on their premolars than do HD pigs, yet there are no significant differences in molar microwear morphology between the dietary groups. Near-significant correlations exist between pit size and dorsoventral bending strength, but only for HD pigs. These results suggest that dietary consistency significantly affects both mandibular structure and dental microwear, yet direct correlations between the two are complicated by a number of factors.

Long Bone Histology and Growth Patterns in Ankylosaurs: Implications for Life History and Evolution

PubMed Central

Stein, Martina; Hayashi, Shoji; Sander, P. Martin

2013-01-01

The ankylosaurs are one of the major dinosaur groups and are characterized by unique body armor. Previous studies on other dinosaur taxa have revealed growth patterns, life history and evolutionary mechanisms based on their long bone histology. However, to date nothing is known about long bone histology in the Ankylosauria. This study is the first description of ankylosaurian long bone histology based on several limb elements, which were sampled from different individuals from the Ankylosauridae and Nodosauridae. The histology is compared to that of other dinosaur groups, including other Thyreophora and Sauropodomorpha. Ankylosaur long bone histology is characterized by a fibrolamellar bone architecture. The bone matrix type in ankylosaurs is closest to that of Stegosaurus. A distinctive mixture of woven and parallel-fibered bone together with overall poor vascularization indicates slow growth rates compared to other dinosaurian taxa. Another peculiar characteristic of ankylosaur bone histology is the extensive remodeling in derived North American taxa. In contrast to other taxa, ankylosaurs substitute large amounts of their primary tissue early in ontogeny. This anomaly may be linked to the late ossification of the ankylosaurian body armor. Metabolically driven remodeling processes must have liberated calcium to ossify the protective osteodermal structures in juveniles to subadult stages, which led to further remodeling due to increased mechanical loading. Abundant structural fibers observed in the primary bone and even in remodeled bone may have improved the mechanical properties of the Haversian bone. PMID:23894321

An enhanced version of a bone-remodelling model based on the continuum damage mechanics theory.

PubMed

Mengoni, M; Ponthot, J P

2015-01-01

The purpose of this work was to propose an enhancement of Doblaré and García's internal bone remodelling model based on the continuum damage mechanics (CDM) theory. In their paper, they stated that the evolution of the internal variables of the bone microstructure, and its incidence on the modification of the elastic constitutive parameters, may be formulated following the principles of CDM, although no actual damage was considered. The resorption and apposition criteria (similar to the damage criterion) were expressed in terms of a mechanical stimulus. However, the resorption criterion is lacking a dimensional consistency with the remodelling rate. We propose here an enhancement to this resorption criterion, insuring the dimensional consistency while retaining the physical properties of the original remodelling model. We then analyse the change in the resorption criterion hypersurface in the stress space for a two-dimensional (2D) analysis. We finally apply the new formulation to analyse the structural evolution of a 2D femur. This analysis gives results consistent with the original model but with a faster and more stable convergence rate.

The timecourse of apoptotic cell death during postnatal remodeling of the mouse cochlea and its premature onset by triiodothyronine (T3).

PubMed

Peeters, R P; Ng, L; Ma, M; Forrest, D

2015-05-15

Apoptosis underlies various forms of tissue remodeling during development. Prior to the onset of hearing, thyroid hormone (T3) promotes cochlear remodeling, which involves regression of the greater epithelial ridge (GER), a transient structure of columnar cells adjacent to the mechanosensory hair cells. We investigated the timecourse of apoptosis in the GER and the influence of ectopic T3 on apoptosis. In saline-treated mice, activated caspase 3-positive cells were detected in the GER between postnatal days 7 and 13 and appeared progressively along the cochlear duct from base to apex over developmental time. T3 given on P0 and P1 advanced the overall program of apoptosis and remodeling by ~4 days. Thyroid hormone receptor β was required for these actions, suggesting a receptor-mediated process of initiation of apoptosis. Finally, T3 given only at P0 or P1 resulted in deafness in adult mice, thus revealing a transient period of susceptibility to long-term damage in the neonatal auditory system. Published by Elsevier Ireland Ltd.

Piezo1 in Smooth Muscle Cells Is Involved in Hypertension-Dependent Arterial Remodeling.

PubMed

Retailleau, Kevin; Duprat, Fabrice; Arhatte, Malika; Ranade, Sanjeev Sumant; Peyronnet, Rémi; Martins, Joana Raquel; Jodar, Martine; Moro, Céline; Offermanns, Stefan; Feng, Yuanyi; Demolombe, Sophie; Patel, Amanda; Honoré, Eric

2015-11-10

The mechanically activated non-selective cation channel Piezo1 is a determinant of vascular architecture during early development. Piezo1-deficient embryos die at midgestation with disorganized blood vessels. However, the role of stretch-activated ion channels (SACs) in arterial smooth muscle cells in the adult remains unknown. Here, we show that Piezo1 is highly expressed in myocytes of small-diameter arteries and that smooth-muscle-specific Piezo1 deletion fully impairs SAC activity. While Piezo1 is dispensable for the arterial myogenic tone, it is involved in the structural remodeling of small arteries. Increased Piezo1 opening has a trophic effect on resistance arteries, influencing both diameter and wall thickness in hypertension. Piezo1 mediates a rise in cytosolic calcium and stimulates activity of transglutaminases, cross-linking enzymes required for the remodeling of small arteries. In conclusion, we have established the connection between an early mechanosensitive process, involving Piezo1 in smooth muscle cells, and a clinically relevant arterial remodeling. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Repurposing Hsp104 to antagonize seminal amyloid and counter HIV infection

PubMed Central

Castellano, Laura M.; Bart, Stephen M.; Holmes, Veronica M.; Weissman, Drew; Shorter, James

2015-01-01

Naturally occurring proteolytic fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120) and semenogelins (SEM1 and 2) form amyloid fibrils in seminal fluid, which capture HIV virions and promote infection. For example, PAP248-286 fibrils, termed SEVI (Semen derived Enhancer of Viral Infection), can potentiate HIV infection by several orders of magnitude. Here, we design three disruptive technologies to rapidly antagonize seminal amyloid by repurposing Hsp104, an amyloid-remodeling nanomachine from yeast. First, Hsp104 and an enhanced engineered variant, Hsp104A503V, directly remodel SEVI and PAP85-120 fibrils into non-amyloid forms. Second, we elucidate catalytically inactive Hsp104 scaffolds that do not remodel amyloid structure, but cluster SEVI, PAP85-120, and SEM1(45-107) fibrils into larger assemblies. Third, we modify Hsp104 to interact with the chambered protease ClpP, which enables coupled remodeling and degradation to irreversibly clear SEVI and PAP85-120 fibrils. Each strategy diminished the ability of seminal amyloid to promote HIV infection and could have therapeutic utility. PMID:26256479

Repurposing Hsp104 to Antagonize Seminal Amyloid and Counter HIV Infection.

PubMed

Castellano, Laura M; Bart, Stephen M; Holmes, Veronica M; Weissman, Drew; Shorter, James

2015-08-20

Naturally occurring proteolytic fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120) and semenogelins (SEM1 and SEM2) form amyloid fibrils in seminal fluid, which capture HIV virions and promote infection. For example, PAP248-286 fibrils, termed SEVI (semen-derived enhancer of viral infection), can potentiate HIV infection by several orders of magnitude. Here, we design three disruptive technologies to rapidly antagonize seminal amyloid by repurposing Hsp104, an amyloid-remodeling nanomachine from yeast. First, Hsp104 and an enhanced engineered variant, Hsp104(A503V), directly remodel SEVI and PAP85-120 fibrils into non-amyloid forms. Second, we elucidate catalytically inactive Hsp104 scaffolds that do not remodel amyloid structure, but cluster SEVI, PAP85-120, and SEM1(45-107) fibrils into larger assemblies. Third, we modify Hsp104 to interact with the chambered protease ClpP, which enables coupled remodeling and degradation to irreversibly clear SEVI and PAP85-120 fibrils. Each strategy diminished the ability of seminal amyloid to promote HIV infection, and could have therapeutic utility. Copyright © 2015 Elsevier Ltd. All rights reserved.

Electron Microscopic Analysis of Hippocampal Axo‐Somatic Synapses in a Chronic Stress Model for Depression

PubMed Central

Csabai, Dávid; Seress, László; Varga, Zsófia; Ábrahám, Hajnalka; Miseta, Attila; Wiborg, Ove

2016-01-01

ABSTRACT Stress can alter the number and morphology of excitatory synapses in the hippocampus, but nothing is known about the effect of stress on inhibitory synapses. Here, we used an animal model for depression, the chronic mild stress model, and quantified the number of perisomatic inhibitory neurons and their synapses. We found reduced density of parvalbumin‐positive (PV+) neurons in response to stress, while the density of cholecystokinin‐immunoreactive (CCK+) neurons was unaffected. We did a detailed electron microscopic analysis to quantify the frequency and morphology of perisomatic inhibitory synapses in the hippocampal CA1 area. We analyzed 1100 CA1 pyramidal neurons and 4800 perisomatic terminals in five control and four chronically stressed rats. In the control animals we observed the following parameters: Number of terminals/soma = 57; Number of terminals/100 µm cell perimeter = 10; Synapse/terminal ratio = 32%; Synapse number/100 terminal = 120; Average terminal length = 920nm. None of these parameters were affected by the stress exposure. Overall, these data indicate that despite the depressive‐like behavior and the decrease in the number of perisomatic PV+ neurons in the light microscopic preparations, the number of perisomatic inhibitory synapses on CA1 pyramidal cells was not affected by stress. In the electron microscope, PV+ neurons and the axon terminals appeared to be normal and we did not find any apoptotic or necrotic cells. This data is in sharp contrast to the remarkable remodeling of the excitatory synapses on spines that has been reported in response to stress and depressive‐like behavior. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27571571

Cardiac mechanics and heart rate variability in patients with systemic sclerosis: the association that we should not miss.

PubMed

Zlatanovic, Maja; Tadic, Marijana; Celic, Vera; Ivanovic, Branislava; Stevanovic, Ana; Damjanov, Nemanja

2017-01-01

We aimed to determine left ventricular (LV) and right ventricular (RV) structure, function and mechanics, as well as heart rate variability (HRV), and their relationship, in patients with systemic sclerosis (SSc). The study included 41 SSc patients and 30 age-matched healthy volunteers. All the patients underwent clinical examination, serological tests, pulmonary function testing, 24-h Holter monitoring and complete two-dimensional echocardiography including strain analysis. The parameters of LV structure (interventricular septum thickness and LV mass index) and RV structure (RV wall thickness) were significantly higher in SSc patients. LV and RV diastolic function (estimated by mitral and tricuspid E/e' ratio) was significantly impaired in SSc group comparing with the healthy controls. LV and RV longitudinal function was significantly deteriorated in SSc patients. LV circumferential strain was also significantly lower in SSc group, whereas LV radial strain was similar between the observed groups. All parameters of time and frequency domain of HRV were decreased in SSc patients. LV and RV cardiac remodeling parameters, particularly diastolic function and longitudinal strain, were associated with HRV indices without regard to the main demographic or the clinical and echocardiographic characteristics. Rodnan Skin Score was also independently associated with biventricular cardiac remodeling in SSc patients. LV and RV structure, function and mechanics, as well as autonomic nervous function, were significantly impaired in SSc patients. There is the significant association between biventricular cardiac remodeling and autonomic function in these patients, which could be useful for their everyday clinical assessment.

Sodium Channel Expression and Localization at Demyelinated Sites in Painful Human Dental Pulp

PubMed Central

Henry, Michael A.; Luo, Songjiang; Foley, Benjamin D.; Rzasa, Rachael S.; Johnson, Lonnie R.; Levinson, S. Rock

2009-01-01

The expression of sodium channels (NaCh(s)) change after inflammatory and nerve lesions and this change has been implicated in the generation of pain states. Here we examine NaCh expression within nerve fibers from normal and painful extracted human teeth with special emphasis on their localization within large accumulations, like those seen at nodes of Ranvier. Pulpal tissue sections from normal wisdom teeth and from teeth with large carious lesions associated with severe and spontaneous pain were double-stained with pan-specific NaCh antibody and caspr (paranodal protein used to visualize nodes of Ranvier) antibody, while additional sections were triple-stained with NaCh, caspr and myelin basic protein (MBP) antibodies. Z-series of images were obtained with the confocal microscope and evaluated with NIH ImageJ software to quantify the density and size of NaCh accumulations, and to characterize NaCh localization at caspr-identified typical and atypical nodal sites. Although the results showed variability in the overall density and size of NaCh accumulations in painful samples, a common finding included the remodeling of NaChs at atypical nodal sites. This remodeling of NaChs included prominent NaCh expression within nerve regions that showed a selective loss of MBP staining in a pattern consistent with a demyelinating process. PMID:19559391

Effects of Estradiol on Learned Helplessness and Associated Remodeling of Hippocampal Spine Synapses in Female Rats

PubMed Central

Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; MacLusky, Neil J; Leranth, Csaba; Duman, Ronald S

2009-01-01

Background Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in females is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant, desipramine. Considering the fact that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life may influence behavioral and synaptic responses to stress and depression. Methods Using electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n=70), under different conditions of estradiol exposure. Results Stress induced an acute and persistent loss of hippocampal spine synapses, while subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either prior to stress or prior to escape testing of nonstressed animals both increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. Conclusions These findings suggest that hippocampal spine synapse remodeling may be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression. PMID:19811775

Responds of Bone Cells to Microgravity: Ground-Based Research

NASA Astrophysics Data System (ADS)

Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

2015-11-01

Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

Age-associated Pro-inflammatory Remodeling and Functional Phenotype in the Heart and Large Arteries

PubMed Central

Wang, Mingyi; Shah, Ajay M

2015-01-01

The aging population is increasing dramatically. Aging–associated stress simultaneously drives proinflammatory remodeling, involving angiotensin II and other factors, in both the heart and large arteries. The structural remodeling and functional changes that occur with aging include cardiac and vascular wall stiffening, systolic hypertension and suboptimal ventricular-arterial coupling, features that are often clinically silent and thus termed a silent syndrome. These age-related effects are the result of responses initiated by cardiovascular proinflammatory cells. Local proinflammatory signals are coupled between the heart and arteries due to common mechanical and humoral messengers within a closed circulating system. Thus, targeting proinflammatory signaling molecules would be a promising approach to improve age-associated suboptimal ventricular-arterial coupling, a major predisposing factor for the pathogenesis of clinical cardiovascular events such as heart failure. PMID:25665458

A new Python library to analyse skeleton images confirms malaria parasite remodelling of the red blood cell membrane skeleton.

PubMed

Nunez-Iglesias, Juan; Blanch, Adam J; Looker, Oliver; Dixon, Matthew W; Tilley, Leann

2018-01-01

We present Skan (Skeleton analysis), a Python library for the analysis of the skeleton structures of objects. It was inspired by the "analyse skeletons" plugin for the Fiji image analysis software, but its extensive Application Programming Interface (API) allows users to examine and manipulate any intermediate data structures produced during the analysis. Further, its use of common Python data structures such as SciPy sparse matrices and pandas data frames opens the results to analysis within the extensive ecosystem of scientific libraries available in Python. We demonstrate the validity of Skan's measurements by comparing its output to the established Analyze Skeletons Fiji plugin, and, with a new scanning electron microscopy (SEM)-based method, we confirm that the malaria parasite Plasmodium falciparum remodels the host red blood cell cytoskeleton, increasing the average distance between spectrin-actin junctions.

Fibrin Clots Are Equilibrium Polymers That Can Be Remodeled Without Proteolytic Digestion

NASA Astrophysics Data System (ADS)

Chernysh, Irina N.; Nagaswami, Chandrasekaran; Purohit, Prashant K.; Weisel, John W.

2012-11-01

Fibrin polymerization is a necessary part of hemostasis but clots can obstruct blood vessels and cause heart attacks and strokes. The polymerization reactions are specific and controlled, involving strong knob-into-hole interactions to convert soluble fibrinogen into insoluble fibrin. It has long been assumed that clots and thrombi are stable structures until proteolytic digestion. On the contrary, using the technique of fluorescence recovery after photobleaching, we demonstrate here that there is turnover of fibrin in an uncrosslinked clot. A peptide representing the knobs involved in fibrin polymerization can compete for the holes and dissolve a preformed fibrin clot, or increase the fraction of soluble oligomers, with striking rearrangements in clot structure. These results imply that in vivo clots or thrombi are more dynamic structures than previously believed that may be remodeled as a result of local environmental conditions, may account for some embolization, and suggest a target for therapeutic intervention.

A new Python library to analyse skeleton images confirms malaria parasite remodelling of the red blood cell membrane skeleton

PubMed Central

Looker, Oliver; Dixon, Matthew W.; Tilley, Leann

2018-01-01

We present Skan (Skeleton analysis), a Python library for the analysis of the skeleton structures of objects. It was inspired by the “analyse skeletons” plugin for the Fiji image analysis software, but its extensive Application Programming Interface (API) allows users to examine and manipulate any intermediate data structures produced during the analysis. Further, its use of common Python data structures such as SciPy sparse matrices and pandas data frames opens the results to analysis within the extensive ecosystem of scientific libraries available in Python. We demonstrate the validity of Skan’s measurements by comparing its output to the established Analyze Skeletons Fiji plugin, and, with a new scanning electron microscopy (SEM)-based method, we confirm that the malaria parasite Plasmodium falciparum remodels the host red blood cell cytoskeleton, increasing the average distance between spectrin-actin junctions. PMID:29472997

Cancer cells incorporate and remodel exogenous palmitate into structural and oncogenic signaling lipids.

PubMed

Louie, Sharon M; Roberts, Lindsay S; Mulvihill, Melinda M; Luo, Kunxin; Nomura, Daniel K

2013-10-01

De novo lipogenesis is considered the primary source of fatty acids for lipid synthesis in cancer cells, even in the presence of exogenous fatty acids. Here, we have used an isotopic fatty acid labeling strategy coupled with metabolomic profiling platforms to comprehensively map palmitic acid incorporation into complex lipids in cancer cells. We show that cancer cells and tumors robustly incorporate and remodel exogenous palmitate into structural and oncogenic glycerophospholipids, sphingolipids, and ether lipids. We also find that fatty acid incorporation into oxidative pathways is reduced in aggressive human cancer cells, and instead shunted into pathways for generating structural and signaling lipids. Our results demonstrate that cancer cells do not solely rely on de novo lipogenesis, but also utilize exogenous fatty acids for generating lipids required for proliferation and protumorigenic lipid signaling. This article is part of a special issue entitled Lipid Metabolism in Cancer. © 2013.

Arterial stiffness and stroke: de-stiffening strategy, a therapeutic target for stroke

PubMed Central

Chen, Yajing; Shen, Fanxia; Liu, Jianrong; Yang, Guo-Yuan

2017-01-01

Stroke is the second leading cause of mortality and morbidity worldwide. Early intervention is of great importance in reducing disease burden. Since the conventional risk factors cannot fully account for the pathogenesis of stroke, it is extremely important to detect useful biomarkers of the vascular disorder for appropriate intervention. Arterial stiffness, a newly recognised reliable feature of arterial structure and function, is demonstrated to be associated with stroke onset and serve as an independent predictor of stroke incidence and poststroke functional outcomes. In this review article, different measurements of arterial stiffness, especially pressure wave velocity, were discussed. We explained the association between arterial stiffness and stroke occurrence by discussing the secondary haemodynamic changes. We reviewed clinical data that support the prediction role of arterial stiffness on stroke. Despite the lack of long-term randomised double-blind controlled therapeutic trials, it is high potential to reduce stroke prevalence through a significant reduction of arterial stiffness (which is called de-stiffening therapy). Pharmacological interventions or lifestyle modification that can influence blood pressure, arterial function or structure in either the short or long term are promising de-stiffening therapies. Here, we summarised different de-stiffening strategies including antihypertension drugs, antihyperlipidaemic agents, chemicals that target arterial remodelling and exercise training. Large and well-designed clinical trials on de-stiffening strategy are needed to testify the prevention effect for stroke. Novel techniques such as modern microscopic imaging and reliable animal models would facilitate the mechanistic analyses in pathophysiology, pharmacology and therapeutics. PMID:28959494

A poroplastic model of structural reorganisation in porous media of biomechanical interest

NASA Astrophysics Data System (ADS)

Grillo, Alfio; Prohl, Raphael; Wittum, Gabriel

2016-03-01

We present a poroplastic model of structural reorganisation in a binary mixture comprising a solid and a fluid phase. The solid phase is the macroscopic representation of a deformable porous medium, which exemplifies the matrix of a biological system (consisting e.g. of cells, extracellular matrix, collagen fibres). The fluid occupies the interstices of the porous medium and is allowed to move throughout it. The system reorganises its internal structure in response to mechanical stimuli. Such structural reorganisation, referred to as remodelling, is described in terms of "plastic" distortions, whose evolution is assumed to obey a phenomenological flow rule driven by stress. We study the influence of remodelling on the mechanical and hydraulic behaviour of the system, showing how the plastic distortions modulate the flow pattern of the fluid, and the distributions of pressure and stress inside it. To accomplish this task, we solve a highly nonlinear set of model equations by elaborating a previously developed numerical procedure, which is implemented in a non-commercial finite element solver.

Insight into structural remodeling of the FlhA ring responsible for bacterial flagellar type III protein export

PubMed Central

2018-01-01

The bacterial flagellum is a supramolecular motility machine. Flagellar assembly begins with the basal body, followed by the hook and finally the filament. A carboxyl-terminal cytoplasmic domain of FlhA (FlhAC) forms a nonameric ring structure in the flagellar type III protein export apparatus and coordinates flagellar protein export with assembly. However, the mechanism of this process remains unknown. We report that a flexible linker of FlhAC (FlhAL) is required not only for FlhAC ring formation but also for substrate specificity switching of the protein export apparatus from the hook protein to the filament protein upon completion of the hook structure. FlhAL was required for cooperative ring formation of FlhAC. Alanine substitutions of residues involved in FlhAC ring formation interfered with the substrate specificity switching, thereby inhibiting filament assembly at the hook tip. These observations lead us to propose a mechanistic model for export switching involving structural remodeling of FlhAC. PMID:29707633

Science 101: How Does an Electron Microscope Work?

ERIC Educational Resources Information Center

Robertson, Bill

2013-01-01

Contrary to popular opinion, electron microscopes are not used to look at electrons. They are used to look for structure in things that are too small to observe with an optical microscope, or to obtain images that are magnified much more than is obtainable with an optical microscope. To understand how electron microscopes work, it will help to go…

Bone Remodeling in Acetabular Reconstruction Using a Kerboull-Type Reinforcement Device and Structural Bone-Grafting in Total Hip Arthroplasty.

PubMed

Oe, Kenichi; Iida, Hirokazu; Tsuda, Kohei; Nakamura, Tomohisa; Okamoto, Naofumi; Ueda, Yusuke

2017-03-01

The purpose of this study was to identify the long-term durability of the Kerboull-type reinforcement device (KT plate) in acetabular reconstruction for massive bone defects, assessing the remodeling of structural bone grafts. This study retrospectively evaluated 106 hips that underwent acetabular reconstruction using a KT plate between November 2000 and December 2010. Thirty-eight primary total hip arthoplasties (THAs) and 68 revised THAs were performed, and the mean duration of clinical follow-up was 8 years (5-14 years). Regarding reconstructing the acetabular bone defects, autografts were used in 37 hips, allografts in 68 hips, and A-W glass ceramics in 2 hips. One hip exhibited radiological migration and no revision for aseptic loosening. The mean Merle d'Aubigné Clinical Score improved from 7.5 points (4-12 points) preoperatively to 10.9 points (9-18 points) at the last follow-up. The Kaplan-Meier survival rate for radiological migration of primary and revised THAs at 10 years was 100% and 97% (95% confidence interval: 96%-100%), respectively. Bone remodeling was evaluated using the radiological demarcation at the bone-to-bone interface, and an improvement of 100% in primary THAs and 94% in revised THAs was observed. For massive bone defects, acetabular reconstruction using the KT plate with a structural bone grafting can yield successful results. Copyright © 2016 Elsevier Inc. All rights reserved.

No overt structural or functional changes associated with PEG-coated gold nanoparticles accumulation with acute exposure in the mouse heart.

PubMed

Yang, Chengzhi; Yang, Hui; Wu, Jimin; Meng, Zenghui; Xing, Rui; Tian, Aiju; Tian, Xin; Guo, Lijun; Zhang, Youyi; Nie, Guangjun; Li, Zijian

2013-10-24

In this study, we investigated the cardiac biodistribution of polyethylene glycol (PEG)-coated AuNPs and their effects on cardiac function, structure and inflammation in both normal and cardiac remodeling mice. The model of cardiac remodeling was induced by subcutaneously injection of isoproterenol (ISO), a non-selective beta-adrenergic agonist, for 7 days. After AuNPs were injected intravenously in mice for 7 consecutive days, Au content in different organs was determined quantitatively by inductively coupled plasma mass spectrometry (ICP-MS), cardiac function and structure were measured by echocardiography, cardiac fibrosis was examined with picrosirius red staining, the morphology of cardiomyocytes was observed with hematoxylin and eosin (H & E) staining. The accumulation of AuNPs in hearts did not affect cardiac function or induce cardiac hypertrophy, cardiac fibrosis and cardiac inflammation under normal physiological condition. Cardiac AuNPs content was 6-fold higher in the cardiac remodeling mouse than normal mice. However, the increased accumulation of AuNPs in the heart did not aggravate ISO-induced cardiac hypertrophy, cardiac fibrosis or cardiac inflammation. These observations suggest that PEG-coated AuNPs possess excellent biocompatibility under both physiological and pathological conditions. Thus, AuNPs may be safe for cardiac patients and hold great promise for further development for various biomedical applications. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Quantification of three-dimensional cell-mediated collagen remodeling using graph theory.

PubMed

Bilgin, Cemal Cagatay; Lund, Amanda W; Can, Ali; Plopper, George E; Yener, Bülent

2010-09-30

Cell cooperation is a critical event during tissue development. We present the first precise metrics to quantify the interaction between mesenchymal stem cells (MSCs) and extra cellular matrix (ECM). In particular, we describe cooperative collagen alignment process with respect to the spatio-temporal organization and function of mesenchymal stem cells in three dimensions. We defined two precise metrics: Collagen Alignment Index and Cell Dissatisfaction Level, for quantitatively tracking type I collagen and fibrillogenesis remodeling by mesenchymal stem cells over time. Computation of these metrics was based on graph theory and vector calculus. The cells and their three dimensional type I collagen microenvironment were modeled by three dimensional cell-graphs and collagen fiber organization was calculated from gradient vectors. With the enhancement of mesenchymal stem cell differentiation, acceleration through different phases was quantitatively demonstrated. The phases were clustered in a statistically significant manner based on collagen organization, with late phases of remodeling by untreated cells clustering strongly with early phases of remodeling by differentiating cells. The experiments were repeated three times to conclude that the metrics could successfully identify critical phases of collagen remodeling that were dependent upon cooperativity within the cell population. Definition of early metrics that are able to predict long-term functionality by linking engineered tissue structure to function is an important step toward optimizing biomaterials for the purposes of regenerative medicine.

CHD3 and CHD4 recruitment and chromatin remodeling activity at DNA breaks is promoted by early poly(ADP-ribose)-dependent chromatin relaxation.

PubMed

Smith, Rebecca; Sellou, Hafida; Chapuis, Catherine; Huet, Sébastien; Timinszky, Gyula

2018-05-04

One of the first events to occur upon DNA damage is the local opening of the compact chromatin architecture, facilitating access of repair proteins to DNA lesions. This early relaxation is triggered by poly(ADP-ribosyl)ation by PARP1 in addition to ATP-dependent chromatin remodeling. CHD4 recruits to DNA breaks in a PAR-dependent manner, although it lacks any recognizable PAR-binding domain, and has the ability to relax chromatin structure. However, its role in chromatin relaxation at the site of DNA damage has not been explored. Using a live cell fluorescence three-hybrid assay, we demonstrate that the recruitment of CHD4 to DNA damage, while being poly(ADP-ribosyl)ation-dependent, is not through binding poly(ADP-ribose). Additionally, we show that CHD3 is recruited to DNA breaks in the same manner as CHD4 and that both CHD3 and CHD4 play active roles in chromatin remodeling at DNA breaks. Together, our findings reveal a two-step mechanism for DNA damage induced chromatin relaxation in which PARP1 and the PAR-binding remodeler activities of Alc1/CHD1L induce an initial chromatin relaxation phase that promotes the subsequent recruitment of CHD3 and CHD4 via binding to DNA for further chromatin remodeling at DNA breaks.

Effects of atorvastatin and losartan on monocrotaline-induced pulmonary artery remodeling in rats.

PubMed

Xie, Liangdi; Lin, Peisen; Xie, Hong; Xu, Changsheng

2010-01-01

Structural remodeling of pulmonary artery plays an important role in maintaining sustained pulmonary arterial hypertension (PAH). The anti-remodeling effects of statins have been reported in systemic hypertension. In this study, we studied the effects of atovastatin (Ato) or losartan (Los) in monocrotaline (MCL)-induced pulmonary artery remodeling using a rat model. Forty Sprague-Dawley (SD) rats were randomly assigned into four groups (n = 10): normal control (Ctr), PAH, PAH treated with Los, and PAH treated with Ato. We found that in the Los- or Ato-treated group, the mean pulmonary arterial pressure, right heart hypertrophy index, ratio of wall/lumen thickness (WT%), as well as the wall/lumen area (WA%) were significantly reduced compared to the PAH group. Also in pulmonary arteries dissected from rats in the Ato- or Los-treated group, in both mRNA and protein levels, the expression of α1C subunit of voltage-gated calcium channel (Ca(v)α1c) was downregulated, while sarcoplasmic/endoplasmic reticulum calcium-ATPase (SERCA-2a) and inositol 1,4,5 triphosphate receptor 1 (IP3R-1) upregulated. However, the mRNA level of RyR-3 subunit of calcium regulating channel was increased, whereas its protein level was reduced in the treated groups. Our results suggest that atorvastatin or losartan may regress the remodeling of the pulmonary artery in pulmonary hypertensive rats, with differential expression of calcium regulating channels.

Protein Kinase Cζ Mediates Insulin-induced Glucose Transport through Actin Remodeling in L6 Muscle Cells

PubMed Central

Liu, Li-Zhong; Zhao, Hai-Lu; Zuo, Jin; Ho, Stanley K.S.; Chan, Juliana C.N.; Meng, Yan; Fang, Fu-De; Tong, Peter C.Y.

2006-01-01

Protein kinase C (PKC) ζ has been implicated in insulin-induced glucose uptake in skeletal muscle cell, although the underlying mechanism remains unknown. In this study, we investigated the effect of PKCζ on actin remodeling and glucose transport in differentiated rat L6 muscle cells expressing myc-tagged glucose transporter 4 (GLUT4). On insulin stimulation, PKCζ translocated from low-density microsomes to plasma membrane accompanied by increase in GLUT4 translocation and glucose uptake. Z-scan confocal microscopy revealed a spatial colocalization of relocated PKCζ with the small GTPase Rac-1, actin, and GLUT4 after insulin stimulation. The insulin-mediated colocalization, PKCζ distribution, GLUT4 translocation, and glucose uptake were inhibited by wortmannin and cell-permeable PKCζ pseudosubstrate peptide. In stable transfected cells, overexpression of PKCζ caused an insulin-like effect on actin remodeling accompanied by a 2.1-fold increase in GLUT4 translocation and 1.7-fold increase in glucose uptake in the absence of insulin. The effects of PKCζ overexpression were abolished by cell-permeable PKCζ pseudosubstrate peptide, but not wortmannin. Transient transfection of constitutively active Rac-1 recruited PKCζ to new structures resembling actin remodeling, whereas dominant negative Rac-1 prevented the insulin-mediated PKCζ translocation. Together, these results suggest that PKCζ mediates insulin effect on glucose transport through actin remodeling in muscle cells. PMID:16525020

Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling

PubMed Central

Makino, Ayako; Firth, Amy L.; Yuan, Jason X.-J.

2017-01-01

The pulmonary circulation is a low resistance and low pressure system. Sustained pulmonary vasoconstriction and excessive vascular remodeling often occur under pathophysiological conditions such as in patients with pulmonary hypertension. Pulmonary vasoconstriction is a consequence of smooth muscle contraction. Many factors released from the endothelium contribute to regulating pulmonary vascular tone, while the extracellular matrix in the adventitia is the major determinant of vascular wall compliance. Pulmonary vascular remodeling is characterized by adventitial and medial hypertrophy due to fibroblast and smooth muscle cell proliferation, neointimal proliferation, intimal, and plexiform lesions that obliterate the lumen, muscularization of precapillary arterioles, and in situ thrombosis. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction, while increased release of mitogenic factors, upregulation (or downregulation) of ion channels and transporters, and abnormalities in intracellular signaling cascades are key to the remodeling of the pulmonary vasculature. Changes in the expression, function, and regulation of ion channels in PASMC and pulmonary arterial endothelial cells play an important role in the regulation of vascular tone and development of vascular remodeling. This article will focus on describing the ion channels and transporters that are involved in the regulation of pulmonary vascular function and structure and illustrating the potential pathogenic role of ion channels and transporters in the development of pulmonary vascular disease. PMID:23733654

Incubation and application of transgenic green fluorescent nude mice in visualization studies on glioma tissue remodeling.

PubMed

Dong, Jun; Dai, Xing-liang; Lu, Zhao-hui; Fei, Xi-feng; Chen, Hua; Zhang, Quan-bin; Zhao, Yao-dong; Wang, Zhi-min; Wang, Ai-dong; Lan, Qing; Huang, Qiang

2012-12-01

The primary reasons for local recurrence and therapeutic failure in the treatment of malignant gliomas are the invasion and interactions of tumor cells with surrounding normal brain cells. However, these tumor cells are hard to be visualized directly in histopathological preparations, or in experimental glioma models. Therefore, we developed an experimental human dual-color in vivo glioma model, which made tracking solitary invasive glioma cells possible, for the purpose of visualizing the interactions between red fluorescence labeled human glioma cells and host brain cells. This may offer references for further studying the roles of tumor microenvironment during glioma tissue remodeling. Transgenic female C57BL/6 mice expressing enhanced green fluorescent protein (EGFP) were crossed with male Balb/c nude mice. Then sib mating was allowed to occur continuously in order to establish an inbred nude mice strain with 50% of their offspring that are EGFP positive. Human glioma cell lines U87-MG and SU3 were transfected with red fluorescent protein (RFP) gene, and a rat C6 glioma cell line was stained directly with CM-DiI, to establish three glioma cell lines emitting red fluorescence (SU3-RFP, U87-RFP, and C6-CM-DiI). Red fluorescence tumor cells were inoculated via intra-cerebral injection into caudate nucleus of the EGFP nude mice. Tumor-bearing mice were sacrificed when their clinical symptoms appeared, and the whole brain was harvested and snap frozen for further analysis. Confocal laser scanning microscopy was performed to monitor the mutual interactions between tumor cells and host brain cells. Almost all the essential tissues of the established EGFP athymic Balb/c nude mice, except hair and erythrocytes, fluoresced green under excitation using a blue light-emitting flashlight with a central peak of 470 nm, approximately 50% of the offsprings were nu/nu EGFP+. SU3-RFP, U87-RFP, and C6-CM-DiI almost 100% expressed red fluorescence under the fluorescence microscope. Under fluorescence microscopic view, RFP+ cells were observed growing wherever they arrived at, locating in the brain parenchyma, ventricles, and para-vascular region. The interactions between the transplanted tumor cells and host adjacent cells could be classified into three types: (1) interweaving; (2) mergence; and (3) fusion. Interweaving was observed in the early stage of tumor remodeling, in which both transplantable tumor cells and host cells were observed scattered in the tumor invading and spreading area without organic connections. Mergence was defined as mutual interactions between tumor cells and host stroma during tumorigenesis. Direct cell fusion between transplantable tumor cells and host cells could be observed occasionally. This study showed that self-established EGFP athymic nude mice offered the possibility of visualizing tumorigenesis of human xenograft tumor, and the dual-color xenograft glioma model was of considerable utility in studying the process of tumor remodeling. Based on this platform, mutual interactions between glioma cells and host tissues could be observed directly to further elucidate the development of tumor microenvironment.

Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state--Implications for the Hepatitis C virus life cycle.

PubMed

Ashworth Briggs, Esther L; Gomes, Rafael G B; Elhussein, Malaz; Collier, William; Findlow, I Stuart; Khalid, Syma; McCormick, Chris J; Williamson, Philip T F

2015-08-01

The non-structural protein 4B (NS4B) from Hepatitis C virus (HCV) plays a pivotal role in the remodelling of the host cell's membranes, required for the formation of the viral replication complex where genome synthesis occurs. NS4B is an integral membrane protein that possesses a number of domains vital for viral replication. Structural and biophysical studies have revealed that one of these, the second amphipathic N-terminal helix (AH2), plays a key role in these remodelling events. However, there is still limited understanding of the mechanism through which AH2 promotes these changes. Here we report on solid-state NMR and molecular dynamics studies that demonstrate that AH2 promotes the clustering of negatively charged lipids within the bilayer, a process that reduces the strain within the bilayer facilitating the remodelling of the lipid bilayer. Furthermore, the presence of negatively charged lipids within the bilayer appears to promote the disassociation of AH2 oligomers, highlighting a potential role for lipid recruitment in regulating NS protein interactions. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Epigenetic regulation and chromatin remodeling in learning and memory.

PubMed

Kim, Somi; Kaang, Bong-Kiun

2017-01-13

Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications. These processes edit genomic properties or the interactions between the genome and histone cores. They then induce structural changes in the chromatin and lead to transcriptional changes of different genes. Recent studies have focused on the concept of chromatin remodeling, which consists of 3D structural changes in chromatin in relation to gene regulation, and is an important process in learning and memory. In this review, we will introduce three major epigenetic processes involved in memory regulation: DNA methylation, histone methylation and histone acetylation. We will also discuss general mechanisms of long-term memory storage and relate the epigenetic control of learning and memory to chromatin remodeling. Finally, we will discuss how epigenetic mechanisms can contribute to the pathologies of neurological disorders and cause memory-related symptoms.

Mars Life? - Microscopic Egg-shaped Structures

NASA Technical Reports Server (NTRS)

1996-01-01

This electron microscope image shows egg-shaped structures, some of which may be possible microscopic fossils of Martian origin as discussed by NASA research published in the Aug. 16, 1996, issue of the journal Science. A two-year investigation found organic molecules, mineral features characteristic of biological activity and possible microscopic fossils such as these inside of an ancient Martian rock that fell to Earth as a meteorite. The largest possible fossils are less than 1/100th the diameter of a human hair in size while most are ten times smaller.

Biomechanical and biophysical environment of bone from the macroscopic to the pericellular and molecular level.

PubMed

Ren, Li; Yang, Pengfei; Wang, Zhe; Zhang, Jian; Ding, Chong; Shang, Peng

2015-10-01

Bones with complicated hierarchical configuration and microstructures constitute the load-bearing system. Mechanical loading plays an essential role in maintaining bone health and regulating bone mechanical adaptation (modeling and remodeling). The whole-bone or sub-region (macroscopic) mechanical signals, including locomotion-induced loading and external actuator-generated vibration, ultrasound, oscillatory skeletal muscle stimulation, etc., give rise to sophisticated and distinct biomechanical and biophysical environments at the pericellular (microscopic) and collagen/mineral molecular (nanoscopic) levels, which are the direct stimulations that positively influence bone adaptation. While under microgravity, the stimulations decrease or even disappear, which exerts a negative influence on bone adaptation. A full understanding of the biomechanical and biophysical environment at different levels is necessary for exploring bone biomechanical properties and mechanical adaptation. In this review, the mechanical transferring theories from the macroscopic to the microscopic and nanoscopic levels are elucidated. First, detailed information of the hierarchical structures and biochemical composition of bone, which are the foundations for mechanical signal propagation, are presented. Second, the deformation feature of load-bearing bone during locomotion is clarified as a combination of bending and torsion rather than simplex bending. The bone matrix strains at microscopic and nanoscopic levels directly induced by bone deformation are critically discussed, and the strain concentration mechanism due to the complicated microstructures is highlighted. Third, the biomechanical and biophysical environments at microscopic and nanoscopic levels positively generated during bone matrix deformation or by dynamic mechanical loadings induced by external actuators, as well as those negatively affected under microgravity, are systematically discussed, including the interstitial fluid flow (IFF) within the lacunar-canalicular system and at the endosteum, the piezoelectricity at the deformed bone surface, and the streaming potential accompanying the IFF. Their generation mechanisms and the regulation effect on bone adaptation are presented. The IFF-induced chemotransport effect, shear stress, and fluid drag on the pericellular matrix are meaningful and noteworthy. Furthermore, we firmly believe that bone adaptation is regulated by the combination of bone biomechanical and biophysical environment, not only the commonly considered matrix strain, fluid shear stress, and hydrostatic pressure, but also the piezoelectricity and streaming potential. Especially, it is necessary to incorporate bone matrix piezoelectricity and streaming potential to explain how osteoblasts (bone formation cells) and osteoclasts (bone resorption cells) can differentiate among different types of loads. Specifically, the regulation effects and the related mechanisms of the biomechanical and biophysical environments on bone need further exploration, and the incorporation of experimental research with theoretical simulations is essential. Copyright © 2015. Published by Elsevier Ltd.

Gene co-expression analysis identifies gene clusters associated with isotropic and polarized growth in Aspergillus fumigatus conidia.

PubMed

Baltussen, Tim J H; Coolen, Jordy P M; Zoll, Jan; Verweij, Paul E; Melchers, Willem J G

2018-04-26

Aspergillus fumigatus is a saprophytic fungus that extensively produces conidia. These microscopic asexually reproductive structures are small enough to reach the lungs. Germination of conidia followed by hyphal growth inside human lungs is a key step in the establishment of infection in immunocompromised patients. RNA-Seq was used to analyze the transcriptome of dormant and germinating A. fumigatus conidia. Construction of a gene co-expression network revealed four gene clusters (modules) correlated with a growth phase (dormant, isotropic growth, polarized growth). Transcripts levels of genes encoding for secondary metabolites were high in dormant conidia. During isotropic growth, transcript levels of genes involved in cell wall modifications increased. Two modules encoding for growth and cell cycle/DNA processing were associated with polarized growth. In addition, the co-expression network was used to identify highly connected intermodular hub genes. These genes may have a pivotal role in the respective module and could therefore be compelling therapeutic targets. Generally, cell wall remodeling is an important process during isotropic and polarized growth, characterized by an increase of transcripts coding for hyphal growth and cell cycle/DNA processing when polarized growth is initiated. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Novel protective role of the circadian nuclear receptor retinoic acid-related orphan receptor-α in diabetic cardiomyopathy.

PubMed

Zhao, Yichao; Xu, Longwei; Ding, Song; Lin, Nan; Ji, Qingqi; Gao, Lingchen; Su, Yuanyuan; He, Ben; Pu, Jun

2017-04-01

Diabetic cardiomyopathy is a major complication that significantly contributes to morbidity and mortality in diabetics with few therapies. Moreover, antidiabetic drugs reported inconsistent or even adverse cardiovascular effects, suggesting that it is important to exploit novel therapeutic targets against diabetic cardiomyopathy. Here, we observed that the nuclear melatonin receptor, the retinoic acid-related orphan receptor-α (RORα), was downregulated in diabetic hearts. By utilizing a mouse line with RORα disruption, we demonstrated that RORα deficiency led to significantly augmented diastolic dysfunction and cardiac remodeling induced by diabetes. Microscopic and molecular analyses further indicated that the detrimental effects of RORα deficiency were associated with aggravated myocardial apoptosis, autophagy dysfunction, and oxidative stress by disrupting antioxidant gene expression. By contrast, restoration of cardiac RORα levels in transgenic mice significantly improved cardiac functional and structural parameters at 8 weeks after diabetes induction. Consistent with genetic manipulation, pharmacological activation of RORα by melatonin and SR1078 (a synthetic agonist) showed beneficial effects against diabetic cardiomyopathy, while the RORα inhibitor SR3335 significantly exacerbated cardiac impairments in diabetic mice. Collectively, these findings suggest that cardiac-targeted manipulation of nuclear melatonin receptor RORα may hold promise for delaying diabetic cardiomyopathy development. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bacterial subversion of host actin dynamics at the plasma membrane.

PubMed

Carabeo, Rey

2011-10-01

Invasion of non-phagocytic cells by a number of bacterial pathogens involves the subversion of the actin cytoskeletal remodelling machinery to produce actin-rich cell surface projections designed to engulf the bacteria. The signalling that occurs to induce these actin-rich structures has considerable overlap among a diverse group of bacteria. The molecular organization within these structures act in concert to internalize the invading pathogen. This dynamic process could be subdivided into three acts - actin recruitment, engulfment, and finally, actin disassembly/internalization. This review will present the current state of knowledge of the molecular processes involved in each stage of bacterial invasion, and provide a perspective that highlights the temporal and spatial control of actin remodelling that occurs during bacterial invasion. © 2011 Blackwell Publishing Ltd.

Cellular growth in plants requires regulation of cell wall biochemistry.

PubMed

Chebli, Youssef; Geitmann, Anja

2017-02-01

Cell and organ morphogenesis in plants are regulated by the chemical structure and mechanical properties of the extracellular matrix, the cell wall. The two primary load bearing components in the plant cell wall, the pectin matrix and the cellulose/xyloglucan network, are constantly remodelled to generate the morphological changes required during plant development. This remodelling is regulated by a plethora of loosening and stiffening agents such as pectin methyl-esterases, calcium ions, expansins, and glucanases. The tight spatio-temporal regulation of the activities of these agents is a sine qua non condition for proper morphogenesis at cell and tissue levels. The pectin matrix and the cellulose-xyloglucan network operate in concert and their behaviour is mutually dependent on their chemical, structural and mechanical modifications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quantitation of maxillary remodeling. 1. A description of osseous changes relative to superimposition on metallic implants.

PubMed

Baumrind, S; Korn, E L; Ben-Bassat, Y; West, E E

1987-01-01

Lateral skull radiographs for a set of 31 human subjects were examined using computer-aided methods in an attempt to quantify modal trends of maxillary remodeling during the mixed dentition and adolescent growth periods. Cumulative changes in position of anterior nasal spine (ANS), posterior nasal spine (PNS), and Point A are reported at annual intervals relative to superimposition on previously placed maxillary metallic implants. This in vivo longitudinal study confirms at a high level of confidence earlier findings by Enlow, Björk, Melsen, and others to the effect that the superior surface of the maxilla remodels downward during the period of growth and development being investigated. However, the inter-individual variability is relatively large, the mean magnitudes of change are relatively small, and the rate of change appears to diminish by 13.5 years. For the 19 subjects for whom data were available for the time interval from 8.5 to 15.5 years, mean downward remodeling at PNS was 2.50 mm with a standard deviation of 2.23 mm. At ANS, corresponding mean value was 1.56 mm with a standard deviation of 2.92 mm. Mean rotation of the ANS-PNS line relative to the implant line was 1.1 degree in the "forward" direction. However, this rotational change was particularly variable with a standard deviation of 4.6 degrees and a range of 11.3 degrees "forward" to 6.7 degrees "backward." The study provides strong evidence that the palate elongates anteroposteriorly mainly by the backward remodeling of structures located posterior to the region in which the implants were placed. There is also evidence that supports the idea of modal resorptive remodeling at ANS and PNS, but here the data are somewhat more equivocal. It appears likely, but not certain, that there are real differences in the modal patterns of remodeling between treated and untreated subjects. Because of problems associated with overfragmentation of the sample, sex differences were not investigated.

Biophysical model of the role of actin remodeling on dendritic spine morphology

PubMed Central

Miermans, C. A.; Kusters, R. P. T.; Hoogenraad, C. C.; Storm, C.

2017-01-01

Dendritic spines are small membranous structures that protrude from the neuronal dendrite. Each spine contains a synaptic contact site that may connect its parent dendrite to the axons of neighboring neurons. Dendritic spines are markedly distinct in shape and size, and certain types of stimulation prompt spines to evolve, in fairly predictable fashion, from thin nascent morphologies to the mushroom-like shapes associated with mature spines. It is well established that the remodeling of spines is strongly dependent upon the actin cytoskeleton inside the spine. A general framework that details the precise role of actin in directing the transitions between the various spine shapes is lacking. We address this issue, and present a quantitative, model-based scenario for spine plasticity validated using realistic and physiologically relevant parameters. Our model points to a crucial role for the actin cytoskeleton. In the early stages of spine formation, the interplay between the elastic properties of the spine membrane and the protrusive forces generated in the actin cytoskeleton propels the incipient spine. In the maturation stage, actin remodeling in the form of the combined dynamics of branched and bundled actin is required to form mature, mushroom-like spines. Importantly, our model shows that constricting the spine-neck aids in the stabilization of mature spines, thus pointing to a role in stabilization and maintenance for additional factors such as ring-like F-actin structures. Taken together, our model provides unique insights into the fundamental role of actin remodeling and polymerization forces during spine formation and maturation. PMID:28158194

Remodeling in bone without osteocytes: Billfish challenge bone structure–function paradigms

PubMed Central

Atkins, Ayelet; Dean, Mason N.; Habegger, Maria Laura; Motta, Phillip J.; Ofer, Lior; Repp, Felix; Shipov, Anna; Weiner, Steve; Currey, John D.; Shahar, Ron

2014-01-01

A remarkable property of tetrapod bone is its ability to detect and remodel areas where damage has accumulated through prolonged use. This process, believed vital to the long-term health of bone, is considered to be initiated and orchestrated by osteocytes, cells within the bone matrix. It is therefore surprising that most extant fishes (neoteleosts) lack osteocytes, suggesting their bones are not constantly repaired, although many species exhibit long lives and high activity levels, factors that should induce considerable fatigue damage with time. Here, we show evidence for active and intense remodeling occurring in the anosteocytic, elongated rostral bones of billfishes (e.g., swordfish, marlins). Despite lacking osteocytes, this tissue exhibits a striking resemblance to the mature bone of large mammals, bearing structural features (overlapping secondary osteons) indicating intensive tissue repair, particularly in areas where high loads are expected. Billfish osteons are an order of magnitude smaller in diameter than mammalian osteons, however, implying that the nature of damage in this bone may be different. Whereas billfish bone material is as stiff as mammalian bone (unlike the bone of other fishes), it is able to withstand much greater strains (relative deformations) before failing. Our data show that fish bone can exhibit far more complex structure and physiology than previously known, and is apparently capable of localized repair even without the osteocytes believed essential for this process. These findings challenge the unique and primary role of osteocytes in bone remodeling, a basic tenet of bone biology, raising the possibility of an alternative mechanism driving this process. PMID:25331870

Structure and Dynamic Properties of a Glucocorticoid Receptor-Induced Chromatin Transition

PubMed Central

Fletcher, Terace M.; Ryu, Byung-Woo; Baumann, Christopher T.; Warren, Barbour S.; Fragoso, Gilberto; John, Sam; Hager, Gordon L.

2000-01-01

Activation of the mouse mammary tumor virus (MMTV) promoter by the glucocorticoid receptor (GR) is associated with a chromatin structural transition in the B nucleosome region of the viral long terminal repeat (LTR). Recent evidence indicates that this transition extends upstream of the B nucleosome, encompassing a region larger than a single nucleosome (G. Fragoso, W. D. Pennie, S. John, and G. L. Hager, Mol. Cell. Biol. 18:3633–3644). We have reconstituted MMTV LTR DNA into a polynucleosome array using Drosophila embryo extracts. We show binding of purified GR to specific GR elements within a large, multinucleosome array and describe a GR-induced nucleoprotein transition that is dependent on ATP and a HeLa nuclear extract. Previously uncharacterized GR binding sites in the upstream C nucleosome region are involved in the extended region of chromatin remodeling. We also show that GR-dependent chromatin remodeling is a multistep process; in the absence of ATP, GR binds to multiple sites on the chromatin array and prevents restriction enzyme access to recognition sites. Upon addition of ATP, GR induces remodeling and a large increase in access to enzymes sites within the transition region. These findings suggest a dynamic model in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, and is then lost from the template. This model is consistent with the recent description of a “hit-and-run” mechanism for GR action in living cells (J. G. McNally, W. G. Müller, D. Walker, and G. L. Hager, Science 287:1262–1264, 2000). PMID:10938123

Phosphorylation of histone H3(T118) alters nucleosome dynamics and remodeling

PubMed Central

North, Justin A.; Javaid, Sarah; Ferdinand, Michelle B.; Chatterjee, Nilanjana; Picking, Jonathan W.; Shoffner, Matthew; Nakkula, Robin J.; Bartholomew, Blaine; Ottesen, Jennifer J.; Fishel, Richard; Poirier, Michael G.

2011-01-01

Nucleosomes, the fundamental units of chromatin structure, are regulators and barriers to transcription, replication and repair. Post-translational modifications (PTMs) of the histone proteins within nucleosomes regulate these DNA processes. Histone H3(T118) is a site of phosphorylation [H3(T118ph)] and is implicated in regulation of transcription and DNA repair. We prepared H3(T118ph) by expressed protein ligation and determined its influence on nucleosome dynamics. We find H3(T118ph) reduces DNA–histone binding by 2 kcal/mol, increases nucleosome mobility by 28-fold and increases DNA accessibility near the dyad region by 6-fold. Moreover, H3(T118ph) increases the rate of hMSH2–hMSH6 nucleosome disassembly and enables nucleosome disassembly by the SWI/SNF chromatin remodeler. These studies suggest that H3(T118ph) directly enhances and may reprogram chromatin remodeling reactions. PMID:21576235

Cellular and molecular basis of RV hypertrophy in congenital heart disease.

PubMed

Iacobazzi, D; Suleiman, M-S; Ghorbel, M; George, S J; Caputo, M; Tulloh, R M

2016-01-01

RV hypertrophy (RVH) is one of the triggers of RV failure in congenital heart disease (CHD). Therefore, improving our understanding of the cellular and molecular basis of this pathology will help in developing strategic therapeutic interventions to enhance patient benefit in the future. This review describes the potential mechanisms that underlie the transition from RVH to RV failure. In particular, it addresses structural and functional remodelling that encompass contractile dysfunction, metabolic changes, shifts in gene expression and extracellular matrix remodelling. Both ischaemic stress and reactive oxygen species production are implicated in triggering these changes and will be discussed. Finally, RV remodelling in response to various CHDs as well as the potential role of biomarkers will be addressed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Automatic analysis for neuron by confocal laser scanning microscope

NASA Astrophysics Data System (ADS)

Satou, Kouhei; Aoki, Yoshimitsu; Mataga, Nobuko; Hensh, Takao K.; Taki, Katuhiko

2005-12-01

The aim of this study is to develop a system that recognizes both the macro- and microscopic configurations of nerve cells and automatically performs the necessary 3-D measurements and functional classification of spines. The acquisition of 3-D images of cranial nerves has been enabled by the use of a confocal laser scanning microscope, although the highly accurate 3-D measurements of the microscopic structures of cranial nerves and their classification based on their configurations have not yet been accomplished. In this study, in order to obtain highly accurate measurements of the microscopic structures of cranial nerves, existing positions of spines were predicted by the 2-D image processing of tomographic images. Next, based on the positions that were predicted on the 2-D images, the positions and configurations of the spines were determined more accurately by 3-D image processing of the volume data. We report the successful construction of an automatic analysis system that uses a coarse-to-fine technique to analyze the microscopic structures of cranial nerves with high speed and accuracy by combining 2-D and 3-D image analyses.

Atomic Structure of Interface States in Silicon Heterojunction Solar Cells

NASA Astrophysics Data System (ADS)

George, B. M.; Behrends, J.; Schnegg, A.; Schulze, T. F.; Fehr, M.; Korte, L.; Rech, B.; Lips, K.; Rohrmüller, M.; Rauls, E.; Schmidt, W. G.; Gerstmann, U.

2013-03-01

Combining orientation dependent electrically detected magnetic resonance and g tensor calculations based on density functional theory we assign microscopic structures to paramagnetic states involved in spin-dependent recombination at the interface of hydrogenated amorphous silicon crystalline silicon (a-Si:H/c-Si) heterojunction solar cells. We find that (i) the interface exhibits microscopic roughness, (ii) the electronic structure of the interface defects is mainly determined by c-Si, (iii) we identify the microscopic origin of the conduction band tail state in the a-Si:H layer, and (iv) present a detailed recombination mechanism.

Astrocyte structural reactivity and plasticity in models of retinal detachment.

PubMed

Luna, Gabriel; Keeley, Patrick W; Reese, Benjamin E; Linberg, Kenneth A; Lewis, Geoffrey P; Fisher, Steven K

2016-09-01

Although retinal neurodegenerative conditions such as age-related macular degeneration, glaucoma, diabetic retinopathy, retinitis pigmentosa, and retinal detachment have different etiologies and pathological characteristics, they also have many responses in common at the cellular level, including neural and glial remodeling. Structural changes in Müller cells, the large radial glia of the retina in retinal disease and injury have been well described, that of the retinal astrocytes remains less so. Using modern imaging technology to describe the structural remodeling of retinal astrocytes after retinal detachment is the focus of this paper. We present both a review of critical literature as well as novel work focusing on the responses of astrocytes following rhegmatogenous and serous retinal detachment. The mouse presents a convenient model system in which to study astrocyte reactivity since the Mϋller cell response is muted in comparison to other species thereby allowing better visualization of the astrocytes. We also show data from rat, cat, squirrel, and human retina demonstrating similarities and differences across species. Our data from immunolabeling and dye-filling experiments demonstrate previously undescribed morphological characteristics of normal astrocytes and changes induced by detachment. Astrocytes not only upregulate GFAP, but structurally remodel, becoming increasingly irregular in appearance, and often penetrating deep into neural retina. Understanding these responses, their consequences, and what drives them may prove to be an important component in improving visual outcome in a variety of therapeutic situations. Our data further supports the concept that astrocytes are important players in the retina's overall response to injury and disease. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of different hip prosthesis shapes considering micro-level bone remodeling and stress-shielding criteria using three-dimensional design space topology optimization.

PubMed

Boyle, Christopher; Kim, Il Yong

2011-06-03

Since the late 1980s, computational analysis of total hip arthroplasty (THA) prosthesis components has been completed using macro-level bone remodeling algorithms. The utilization of macro-sized elements requires apparent bone densities to predict cancellous bone strength, thereby, preventing visualization and analysis of realistic trabecular architecture. In this study, we utilized a recently developed structural optimization algorithm, design space optimization (DSO), to perform a micro-level three-dimensional finite element bone remodeling simulation on the human proximal femur pre- and post-THA. The computational simulation facilitated direct performance comparison between two commercially available prosthetic implant stems from Zimmer Inc.: the Alloclassic and the Mayo conservative. The novel micro-level approach allowed the unique ability to visualize the trabecular bone adaption post-operation and to quantify the changes in bone mineral content by region. Stress-shielding and strain energy distribution were also quantified for the immediate post-operation and the stably fixated, post-remodeling conditions. Stress-shielding was highest in the proximal region and remained unchanged post-remodeling; conversely, the mid and distal portions show large increases in stress, suggesting a distal shift in the loadpath. The Mayo design conserves bone mass, while simultaneously reducing the incidence of stress-shielding compared to the Alloclassic, revealing a key benefit of the distinctive geometry. Several important factors for stable fixation, determined in clinical evaluations from the literature, were evident in both designs: high levels of proximal bone loss and distal bone densification. The results suggest this novel computational framework can be utilized for comparative hip prosthesis shape, uniquely considering the post-operation bone remodeling as a design criterion. Copyright © 2011 Elsevier Ltd. All rights reserved.

Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning: role of protein kinase B/Akt signaling.

PubMed

Feng, Jianhua; Fischer, Gregor; Lucchinetti, Eliana; Zhu, Min; Bestmann, Lukas; Jegger, David; Arras, Margarete; Pasch, Thomas; Perriard, Jean-Claude; Schaub, Marcus C; Zaugg, Michael

2006-05-01

Postinfarct remodeled myocardium exhibits numerous structural and biochemical alterations. So far, it is unknown whether postconditioning elicited by volatile anesthetics can also provide protection in the remodeled myocardium. Myocardial infarct was induced in male Wistar rats by ligation of the left anterior descending coronary artery. Six weeks later, hearts were buffer-perfused and exposed to 40 min of ischemia followed by 90 min of reperfusion. Anesthetic postconditioning was induced by 15 min of 2.1 vol% isoflurane. In some experiments, LY294002 (15 microM), a phosphatidylinositol 3-kinase inhibitor, was coadministered with isoflurane. Masson's trichrome staining, immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction served to confirm remodeling. In buffer-perfused hearts, functional recovery was recorded, and acute infarct size was measured using 1% triphenyltetrazolium chloride staining and lactate dehydrogenase release during reperfusion. Western blot analysis was used to determine phosphorylation of reperfusion injury salvage kinases including protein kinase B/Akt and its downstream targets after 15 min of reperfusion. Infarct hearts exhibited typical macroscopic and molecular changes of remodeling. Isoflurane postconditioning improved functional recovery and decreased acute infarct size, as determined by triphenyltetrazolium (35 +/- 5% in unprotected hearts vs. 8 +/- 3% in anesthetic postconditioning; P < 0.05) and lactate dehydrogenase release. This protection was abolished by LY294002, which inhibited phosphorylation of protein kinase B/Akt and its downstream targets glycogen synthase kinase 3beta, endothelial nitric oxide synthase, and p70S6 kinase. Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning via protein kinase B/Akt signaling. This is the first time to demonstrate that anesthetic postconditioning retains its marked protection in diseased myocardium.

Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction.

PubMed

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

2016-11-01

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.

Remodeling of muscle fibers approaching the human myotendinous junction.

PubMed

Jakobsen, J R; Jakobsen, N R; Mackey, A L; Koch, M; Kjaer, M; Krogsgaard, M R

2018-04-19

The myotendinous junction (MTJ) is at high risk of strain injuries, due to high amounts of energy that is transferred through this structure. The risk of strain injury is significantly reduced by heavy resistance training (HRT), indicating a remodeling capacity of MTJ. We investigated the degree of remodeling of muscle fibers near the human MTJ. In 8 individuals, samples were taken from the semitendinosus and gracilis MTJ and they were stained immunohistochemically for myonuclei (DAPI), fibroblasts (TCF7L2), and satellite cells (CD56). A high portion of the muscle fibers adjacent to the MTJ contained a centrally located myonucleus (47 ± 8%, mean ± SD) and half of the muscle fibers were CD56 positive. The number of satellite cells and fibroblasts were not higher than what has previously been reported from muscle bellies. The immunohistochemical findings suggest that the rate of remodeling of muscle fibers near the MTJ is very high. The finding that there was no increased number of satellite cells and fibroblasts could be explained as a dynamic phenomenon. The effect of HRT should be evaluated in a randomized setting. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

T Lymphocyte Migration: An Action Movie Starring the Actin and Associated Actors.

PubMed

Dupré, Loïc; Houmadi, Raïssa; Tang, Catherine; Rey-Barroso, Javier

2015-01-01

The actin cytoskeleton is composed of a dynamic filament meshwork that builds the architecture of the cell to sustain its fundamental properties. This physical structure is characterized by a continuous remodeling, which allows cells to accomplish complex motility steps such as directed migration, crossing of biological barriers, and interaction with other cells. T lymphocytes excel in these motility steps to ensure their immune surveillance duties. In particular, actin cytoskeleton remodeling is a key to facilitate the journey of T lymphocytes through distinct tissue environments and to tune their stop and go behavior during the scanning of antigen-presenting cells. The molecular mechanisms controlling actin cytoskeleton remodeling during T lymphocyte motility have been only partially unraveled, since the function of many actin regulators has not yet been assessed in these cells. Our review aims to integrate the current knowledge into a comprehensive picture of how the actin cytoskeleton drives T lymphocyte migration. We will present the molecular actors that control actin cytoskeleton remodeling, as well as their role in the different T lymphocyte motile steps. We will also highlight which challenges remain to be addressed experimentally and which approaches appear promising to tackle them.

Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome.

PubMed

Gao, Ling; Cao, Jia-Tian; Liang, Yan; Zhao, Yi-Chao; Lin, Xian-Hua; Li, Xiao-Cui; Tan, Ya-Jing; Li, Jing-Yi; Zhou, Cheng-Liang; Xu, Hai-Yan; Sheng, Jian-Zhong; Huang, He-Feng

2016-05-01

Polycystic ovary syndrome (PCOS) is a complex reproductive and metabolic disorder affecting 10 % of reproductive-aged women, and is well associated with an increased prevalence of cardiovascular risk factors. However, there are few data concerning the direct association of PCOS with cardiac pathologies. The present study aims to investigate the changes in cardiac structure, function, and cardiomyocyte survival in a PCOS model, and explore the possible effect of calcitriol administration on these changes. PCOS was induced in C57BL/6J female mice by chronic dihydrotestosterone administration, as evidenced by irregular estrous cycles, obesity and dyslipidemia. PCOS mice progressively developed cardiac abnormalities including cardiac hypertrophy, interstitial fibrosis, myocardial apoptosis, and cardiac dysfunction. Conversely, concomitant administration of calcitriol significantly attenuated cardiac remodeling and cardiomyocyte apoptosis, and improved cardiac function. Molecular analysis revealed that the beneficial effect of calcitriol was associated with normalized autophagy function by increasing phosphorylation levels of AMP-activated protein kinase and inhibiting phosphorylation levels of mammalian target of rapamycin complex. Our findings provide the first evidence for the presence of cardiac remodeling in a PCOS model, and vitamin D supplementation may be a potential therapeutic strategy for the prevention and treatment of PCOS-related cardiac remodeling.

Secretagogue stimulation of neurosecretory cells elicits filopodial extensions uncovering new functional release sites.

PubMed

Papadopulos, Andreas; Martin, Sally; Tomatis, Vanesa M; Gormal, Rachel S; Meunier, Frederic A

2013-12-04

Regulated exocytosis in neurosecretory cells relies on the timely fusion of secretory granules (SGs) with the plasma membrane. Secretagogue stimulation leads to an enlargement of the cell footprint (surface area in contact with the coverslip), an effect previously attributed to exocytic fusion of SGs with the plasma membrane. Using total internal reflection fluorescence microscopy, we reveal the formation of filopodia-like structures in bovine chromaffin and PC12 cells driving the footprint expansion, suggesting the involvement of cortical actin network remodeling in this process. Using exocytosis-incompetent PC12 cells, we demonstrate that footprint enlargement is largely independent of SG fusion, suggesting that vesicular exocytic fusion plays a relatively minor role in filopodial expansion. The footprint periphery, including filopodia, undergoes extensive F-actin remodeling, an effect abolished by the actomyosin inhibitors cytochalasin D and blebbistatin. Imaging of both Lifeact-GFP and the SG marker protein neuropeptide Y-mCherry reveals that SGs actively translocate along newly forming actin tracks before undergoing fusion. Together, these data demonstrate that neurosecretory cells regulate the number of SGs undergoing exocytosis during sustained stimulation by controlling vesicular mobilization and translocation to the plasma membrane through actin remodeling. Such remodeling facilitates the de novo formation of fusion sites.

Matrix metalloproteinases: their biological functions and clinical implications.

PubMed

Hijova, E

2005-01-01

Matrix metalloproteinases (MMPs), which are also known as matrixins, are proteinases that participate in extracellular matrix remodelling and degradation. Under normal physiological conditions, the activities of MMPs are precisely regulated at the level of transcription, at that of activation of the pro-MMP precursor zymogenes as well as at that of inhibition by endogenous inhibitors (tissue inhibitors of metalloproteinases, TIMPs). Alterations in the regulation of MMP activity are implicated in diseases such as cancer, fibrosis, arthritis and atherosclerosis. The pathological effects of MMPs and TIMPs in cardiovascular diseases involve vascular remodelling, atherosclerotic plaque instability and cardiac remodelling in congestive heart failure or after myocardial infarction. Since excessive tissue remodelling and increased matrix metalloproteinases activity have been demonstrated during atherosclerotic lesion progression (including plaque disruption), MMPs represent a potential target for therapeutic intervention aimed at the modification of vascular pathology by restoring the physiological balance between MMPs and TIMPs. Recent findings suggest that MMPs are also involved in cancer initiation, invasion and metastasis; MMP inhibitors could be considered for evaluation as cancer chemopreventive molecules. This review describes the members of MMP and TIMP families and discusses the structure, function and regulation of MMP activity. (Tab. 1, Ref: 45.)

Frontiers in growth and remodeling

PubMed Central

Menzel, Andreas; Kuhl, Ellen

2012-01-01

Unlike common engineering materials, living matter can autonomously respond to environmental changes. Living structures can grow stronger, weaker, larger, or smaller within months, weeks, or days as a result of a continuous microstructural turnover and renewal. Hard tissues can adapt by increasing their density and grow strong. Soft tissues can adapt by increasing their volume and grow large. For more than three decades, the mechanics community has actively contributed to understand the phenomena of growth and remodeling from a mechanistic point of view. However, to date, there is no single, unified characterization of growth, which is equally accepted by all scientists in the field. Here we shed light on the continuum modeling of growth and remodeling of living matter, and give a comprehensive overview of historical developments and trends. We provide a state-of-the-art review of current research highlights, and discuss challenges and potential future directions. Using the example of volumetric growth, we illustrate how we can establish and utilize growth theories to characterize the functional adaptation of soft living matter. We anticipate this review to be the starting point for critical discussions and future research in growth and remodeling, with a potential impact on life science and medicine. PMID:22919118

Microvascular Remodeling and Wound Healing: A Role for Pericytes

PubMed Central

Dulmovits, Brian M.; Herman, Ira M.

2012-01-01

Physiologic wound healing is highly dependent on the coordinated functions of vascular and non-vascular cells. Resolution of tissue injury involves coagulation, inflammation, formation of granulation tissue, remodeling and scarring. Angiogenesis, the growth of microvessels the size of capillaries, is crucial for these processes, delivering blood-borne cells, nutrients and oxygen to actively remodeling areas. Central to angiogenic induction and regulation is microvascular remodeling, which is dependent upon capillary endothelial cell and pericyte interactions. Despite our growing knowledge of pericyte-endothelial cell crosstalk, it is unclear how the interplay among pericytes, inflammatory cells, glia and connective tissue elements shape microvascular injury response. Here, we consider the relationships that pericytes form with the cellular effectors of healing in normal and diabetic environments, including repair following injury and vascular complications of diabetes, such as diabetic macular edema and proliferative diabetic retinopathy. In addition, pericytes and stem cells possessing “pericyte-like” characteristics are gaining considerable attention in experimental and clinical efforts aimed at promoting healing or eradicating ocular vascular proliferative disorders. As the origin, identification and characterization of microvascular pericyte progenitor populations remains somewhat ambiguous, the molecular markers, structural and functional characteristics of pericytes will be briefly reviewed. PMID:22750474

Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation

PubMed Central

Phan, Mimi L.; Bieszczad, Kasia M.

2016-01-01

Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded. PMID:26881129

Molecular engineering of colloidal liquid crystals using DNA origami

NASA Astrophysics Data System (ADS)

Siavashpouri, Mahsa; Wachauf, Christian; Zakhary, Mark; Praetorius, Florian; Dietz, Hendrik; Dogic, Zvonimir

Understanding the microscopic origin of cholesteric phase remains a foundational, yet unresolved problem in the field of liquid crystals. Lack of experimental model system that allows for the systematic control of the microscopic chiral structure makes it difficult to investigate this problem for several years. Here, using DNA origami technology, we systematically vary the chirality of the colloidal particles with molecular precision and establish a quantitative relationship between the microscopic structure of particles and the macroscopic cholesteric pitch. Our study presents a new methodology for predicting bulk behavior of diverse phases based on the microscopic architectures of the constituent molecules.

Spectral confocal reflection microscopy using a white light source

NASA Astrophysics Data System (ADS)

Booth, M.; Juškaitis, R.; Wilson, T.

2008-08-01

We present a reflection confocal microscope incorporating a white light supercontinuum source and spectral detection. The microscope provides images resolved spatially in three-dimensions, in addition to spectral resolution covering the wavelength range 450-650nm. Images and reflection spectra of artificial and natural specimens are presented, showing features that are not normally revealed in conventional microscopes or confocal microscopes using discrete line lasers. The specimens include thin film structures on semiconductor chips, iridescent structures in Papilio blumei butterfly scales, nacre from abalone shells and opal gemstones. Quantitative size and refractive index measurements of transparent beads are derived from spectral interference bands.

Mars Life? - Microscopic Structures

NASA Technical Reports Server (NTRS)

1996-01-01

In the center of this electron microscope image of a small chip from a meteorite are several tiny structures that are possible microscopic fossils of primitive, bacteria-like organisms that may have lived on Mars more than 3.6 billion years ago. A two-year investigation by a NASA research team found organic molecules, mineral features characteristic of biological activity and possible microscopic fossils such as these inside of an ancient Martian rock that fell to Earth as a meteorite. The largest possible fossils are less than 1/100th the diameter of a human hair in size while most are ten times smaller.

Race-related differences in left ventricular structural and functional remodeling in response to increased afterload: the Atherosclerosis Risk in Communities Study

PubMed Central

Fernandes-Silva, Miguel M; Shah, Amil M; Hegde, Sheila; Goncalves, Alexandra; Claggett, Brian; Cheng, Susan; Nadruz, Wilson; Kitzman, Dalane W.; Konety, Suma H.; Matsushita, Kunihiro; Mosley, Thomas; Lam, Carolyn S.P.; Borlaug, Barry A.; Solomon, Scott D

2016-01-01

Background Chronic increasing in arterial afterload may be an important trigger for left ventricular (LV) remodeling and dysfunction that lead to heart failure (HF). Racial differences in the predisposition to HF are well described, but the underlying mechanisms remain unclear. Objective We evaluated the racial differences in arterial elastance (Ea), which reflects the arterial afterload faced by the LV, and its associations with cardiac structure and function. We hypothesize that the LV in blacks displays heightened afterload sensitivity as compared to whites. Methods We studied 5727 community-based, elderly Atherosclerosis Risk in Community (ARIC) Study participants (22% black), who underwent echocardiography between 2011 and 2013. Results Blacks were younger (75 ± 5 vs 76 ± 5 years old), more frequently women (66 vs 57%), and had higher prevalence of obesity (46 vs 31%), hypertension (94 vs 80%), and diabetes mellitus (47 vs 34%) than whites. Adjusting for these baseline differences, Ea was higher among blacks (1.96 ± 0.01 vs 1.80 ± 0.01 mmHg/mL). In blacks, Ea was associated with greater LV remodeling (LV mass index, β = 3.21 ± 0.55 g/m2, p<0.001) and higher LV filling pressures (E/e′ ratio, β = 0.42 ± 0.11, p<0.001). These relationships were not observed in whites (LV mass, β = 0.16 ± 0.32 g/m2, p=0.61, p for interaction <0.001; E/e′ratio, β = −0.32 ± 0.06, p<0.001, p for interaction <0.001).. Conclusion These community-based data suggest that black Americans display heightened afterload sensitivity as a stimulus for LV structural and functional remodeling, which may contribute to their greater risk of HF, as compared to white Americans. PMID:28017356

Increased expression of NF-AT3 and NF-AT4 in the atria correlates with procollagen I carboxyl terminal peptide and TGF-β1 levels in serum of patients with atrial fibrillation.

PubMed

Zhao, Fei; Zhang, ShiJiang; Chen, YiJiang; Gu, WeiDong; Ni, BuQing; Shao, YongFeng; Wu, YanHu; Qin, JianWei

2014-11-25

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Unfortunately, the precise mechanisms and sensitive serum biomarkers of atrial remodeling in AF remain unclear. The aim of this study was to determine whether the expression of the transcription factors NF-AT3 and NF-AT4 correlate with atrial structural remodeling of atrial fibrillation and serum markers for collagen I and III synthesis. Right and left atrial specimens were obtained from 90 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (n = 30), paroxysmal atrial fibrillation (n = 30), and persistent atrial fibrillation (n = 30) groups. NF-AT3, NF-AT4, and collagen I and III mRNA and protein expression in atria were measured. We also tested the levels of the carboxyl-terminal peptide from pro-collagen I, the N-terminal type I procollagen propeptides, the N-terminal type III procollagen propeptides, and TGF-β1 in serum using an enzyme immunosorbent assay. NF-AT3 and NF-AT4 mRNA and protein expression were increased in the AF groups, especially in the left atrium. NF-AT3 and NF-AT4 expression in the right atrium was increased in the persistent atrial fibrillation group compared the sinus rhythm group with similar valvular disease. In patients with AF, the expression levels of nuclear NF-AT3 and NF-AT4 correlated with those of collagens I and III in the atria and with PICP and TGF-β1 in blood. These data support the hypothesis that nuclear NF-AT3 and NF-AT4 participates in atrial structural remodeling, and that PICP and TGF-β1 levels may be sensitive serum biomarkers to estimate atrial structural remodeling with atrial fibrillation.

Life-History Traits of the Miocene Hipparion concudense (Spain) Inferred from Bone Histological Structure

PubMed Central

Martinez-Maza, Cayetana; Alberdi, Maria Teresa; Nieto-Diaz, Manuel; Prado, José Luis

2014-01-01

Histological analyses of fossil bones have provided clues on the growth patterns and life history traits of several extinct vertebrates that would be unavailable for classical morphological studies. We analyzed the bone histology of Hipparion to infer features of its life history traits and growth pattern. Microscope analysis of thin sections of a large sample of humeri, femora, tibiae and metapodials of Hipparion concudense from the upper Miocene site of Los Valles de Fuentidueña (Segovia, Spain) has shown that the number of growth marks is similar among the different limb bones, suggesting that equivalent skeletochronological inferences for this Hipparion population might be achieved by means of any of the elements studied. Considering their abundance, we conducted a skeletechronological study based on the large sample of third metapodials from Los Valles de Fuentidueña together with another large sample from the Upper Miocene locality of Concud (Teruel, Spain). The data obtained enabled us to distinguish four age groups in both samples and to determine that Hipparion concudense tended to reach skeletal maturity during its third year of life. Integration of bone microstructure and skeletochronological data allowed us to identify ontogenetic changes in bone structure and growth rate and to distinguish three histologic ontogenetic stages corresponding to immature, subadult and adult individuals. Data on secondary osteon density revealed an increase in bone remodeling throughout the ontogenetic stages and a lesser degree thereof in the Concud population, which indicates different biomechanical stresses in the two populations, likely due to environmental differences. Several individuals showed atypical growth patterns in the Concud sample, which may also reflect environmental differences between the two localities. Finally, classification of the specimens’ age within groups enabled us to characterize the age structure of both samples, which is typical of attritional assemblages. PMID:25098950

BAF53b, a Neuron-Specific Nucleosome Remodeling Factor, Is Induced after Learning and Facilitates Long-Term Memory Consolidation.

PubMed

Yoo, Miran; Choi, Kwang-Yeon; Kim, Jieun; Kim, Mujun; Shim, Jaehoon; Choi, Jun-Hyeok; Cho, Hye-Yeon; Oh, Jung-Pyo; Kim, Hyung-Su; Kaang, Bong-Kiun; Han, Jin-Hee

2017-03-29

Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role of nucleosome-remodeling is largely unexplored. Recent studies show that the functional loss of BAF53b, a postmitotic neuron-specific subunit of the BAF nucleosome-remodeling complex, results in the deficit of consolidation of hippocampus-dependent memory and cocaine-associated memory in the rodent brain. However, it is unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain site for fear memory encoding and storage. To address these questions, we used viral vector approaches to either decrease or increase BAF53b function specifically in the lateral amygdala of adult mice in auditory fear conditioning paradigm. Knockdown of Baf53b before training disrupted long-term memory formation with no effect on short-term memory, basal synaptic transmission, and spine structures. We observed in our qPCR analysis that BAF53b was induced in the lateral amygdala neurons at the late consolidation phase after fear conditioning. Moreover, transient BAF53b overexpression led to persistently enhanced memory formation, which was accompanied by increase in thin-type spine density. Together, our results provide the evidence that BAF53b is induced after learning, and show that such increase of BAF53b level facilitates memory consolidation likely by regulating learning-related spine structural plasticity. SIGNIFICANCE STATEMENT Recent works in the rodent brain begin to link nucleosome remodeling-dependent epigenetic mechanism to memory consolidation. Here we show that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced in the lateral amygdala neurons at the late phase of consolidation after fear conditioning. Using specific gene knockdown or overexpression approaches, we identify the critical role of BAF53b in the lateral amygdala neurons for memory consolidation during long-term memory formation. Our results thus provide an idea about how nucleosome remodeling can be regulated during long-term memory formation and contributes to the permanent storage of associative fear memory in the lateral amygdala, which is relevant to fear and anxiety-related mental disorders. Copyright © 2017 the authors 0270-6474/17/373686-12$15.00/0.

9 CFR 355.18 - Drawings and specifications to be furnished.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION... specifications for remodeling inspected plants or for new structures at such plants shall be submitted to the...

CHD chromatin remodelers and the transcription cycle

PubMed Central

Murawska, Magdalena

2011-01-01

It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by “opening” or “closing” chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but also are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts. PMID:22223048

Mechanistic insight into prolonged electromechanical delay in dyssynchronous heart failure: a computational study

PubMed Central

Constantino, Jason; Hu, Yuxuan; Lardo, Albert C.

2013-01-01

In addition to the left bundle branch block type of electrical activation, there are further remodeling aspects associated with dyssynchronous heart failure (HF) that affect the electromechanical behavior of the heart. Among the most important are altered ventricular structure (both geometry and fiber/sheet orientation), abnormal Ca2+ handling, slowed conduction, and reduced wall stiffness. In dyssynchronous HF, the electromechanical delay (EMD), the time interval between local myocyte depolarization and myofiber shortening onset, is prolonged. However, the contributions of the four major HF remodeling aspects in extending EMD in the dyssynchronous failing heart remain unknown. The goal of this study was to determine the individual and combined contributions of HF-induced remodeling aspects to EMD prolongation. We used MRI-based models of dyssynchronous nonfailing and HF canine electromechanics and constructed additional models in which varying combinations of the four remodeling aspects were represented. A left bundle branch block electrical activation sequence was simulated in all models. The simulation results revealed that deranged Ca2+ handling is the primary culprit in extending EMD in dyssynchronous HF, with the other aspects of remodeling contributing insignificantly. Mechanistically, we found that abnormal Ca2+ handling in dyssynchronous HF slows myofiber shortening velocity at the early-activated septum and depresses both myofiber shortening and stretch rate at the late-activated lateral wall. These changes in myofiber dynamics delay the onset of myofiber shortening, thus giving rise to prolonged EMD in dyssynchronous HF. PMID:23934857

Synaptic remodeling generates synchronous oscillations in the degenerated outer mouse retina

PubMed Central

Haq, Wadood; Arango-Gonzalez, Blanca; Zrenner, Eberhart; Euler, Thomas; Schubert, Timm

2014-01-01

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

The δ isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload

PubMed Central

Backs, Johannes; Backs, Thea; Neef, Stefan; Kreusser, Michael M.; Lehmann, Lorenz H.; Patrick, David M.; Grueter, Chad E.; Qi, Xiaoxia; Richardson, James A.; Hill, Joseph A.; Katus, Hugo A.; Bassel-Duby, Rhonda; Maier, Lars S.; Olson, Eric N.

2009-01-01

Acute and chronic injuries to the heart result in perturbation of intracellular calcium signaling, which leads to pathological cardiac hypertrophy and remodeling. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the transduction of calcium signals in the heart, but the specific isoforms of CaMKII that mediate pathological cardiac signaling have not been fully defined. To investigate the potential involvement in heart disease of CaMKIIδ, the major CaMKII isoform expressed in the heart, we generated CaMKIIδ-null mice. These mice are viable and display no overt abnormalities in cardiac structure or function in the absence of stress. However, pathological cardiac hypertrophy and remodeling are attenuated in response to pressure overload in these animals. Cardiac extracts from CaMKIIδ-null mice showed diminished kinase activity toward histone deacetylase 4 (HDAC4), a substrate of stress-responsive protein kinases and suppressor of stress-dependent cardiac remodeling. In contrast, phosphorylation of the closely related HDAC5 was unaffected in hearts of CaMKIIδ-null mice, underscoring the specificity of the CaMKIIδ signaling pathway for HDAC4 phosphorylation. We conclude that CaMKIIδ functions as an important transducer of stress stimuli involved in pathological cardiac remodeling in vivo, which is mediated, at least in part, by the phosphorylation of HDAC4. These findings point to CaMKIIδ as a potential therapeutic target for the maintenance of cardiac function in the setting of pressure overload. PMID:19179290

The Chromatin Remodeling Factor SMARCB1 Forms a Complex with Human Cytomegalovirus Proteins UL114 and UL44

PubMed Central

Ranneberg-Nilsen, Toril; Rollag, Halvor; Slettebakk, Ragnhild; Backe, Paul Hoff; Olsen, Øyvind; Luna, Luisa; Bjørås, Magnar

2012-01-01

Background Human cytomegalovirus (HCMV) uracil DNA glycosylase, UL114, is required for efficient viral DNA replication. Presumably, UL114 functions as a structural partner to other factors of the DNA-replication machinery and not as a DNA repair protein. UL114 binds UL44 (HCMV processivity factor) and UL54 (HCMV-DNA-polymerase). In the present study we have searched for cellular partners of UL114. Methodology/Principal Findings In a yeast two-hybrid screen SMARCB1, a factor of the SWI/SNF chromatin remodeling complex, was found to be an interacting partner of UL114. This interaction was confirmed in vitro by co-immunoprecipitation and pull-down. Immunofluorescence microscopy revealed that SMARCB1 along with BRG-1, BAF170 and BAF155, which are the core SWI/SNF components required for efficient chromatin remodeling, were present in virus replication foci 24–48 hours post infection (hpi). Furthermore a direct interaction was also demonstrated for SMARCB1 and UL44. Conclusions/Significance The core SWI/SNF factors required for efficient chromatin remodeling are present in the HCMV replication foci throughout infection. The proteins UL44 and UL114 interact with SMARCB1 and may participate in the recruitment of the SWI/SNF complex to the chromatinized virus DNA. Thus, the presence of the SWI/SNF chromatin remodeling complex in replication foci and its association with UL114 and with UL44 might imply its involvement in different DNA transactions. PMID:22479537

Development of the field of structural physiology

PubMed Central

FUJIYOSHI, Yoshinori

2015-01-01

Electron crystallography is especially useful for studying the structure and function of membrane proteins — key molecules with important functions in neural and other cells. Electron crystallography is now an established technique for analyzing the structures of membrane proteins in lipid bilayers that closely simulate their natural biological environment. Utilizing cryo-electron microscopes with helium-cooled specimen stages that were developed through a personal motivation to understand the functions of neural systems from a structural point of view, the structures of membrane proteins can be analyzed at a higher than 3 Å resolution. This review covers four objectives. First, I introduce the new research field of structural physiology. Second, I recount some of the struggles involved in developing cryo-electron microscopes. Third, I review the structural and functional analyses of membrane proteins mainly by electron crystallography using cryo-electron microscopes. Finally, I discuss multifunctional channels named “adhennels” based on structures analyzed using electron and X-ray crystallography. PMID:26560835

[Osteostimulating effect of bone xenograft on bone tissue regeneration].

PubMed

Balin, V N; Balin, D V; Iordanishvili, A K; Musikin, M I

2015-01-01

The aim of experimental case-control study performed in 28 dogs divided in 2 groups was to assess local tissue reactions on bone xenograft transplantation; dynamics of bone remodeling and formation at the site of bone defect wall contacting with bone xenograft; dynamics and mechanisms of xenograft remodeling. Transplantation of xenograft in conventional bone defects did not cause inflammatory of destructive reactions because of high biocompatibility of the material. At transplantation site active fibrous bone trabeculae formation filling the spaces between xenograft participles was observed. On the 90th day newly formed bone showed lammelar structure. Simultaneously from the 42d day the invasion of cell elements from recipient bed into the material was seen leading to xenograft resorption. The observed dynamics may be assessed as gradual substitution of xenograft with newly formed host bone structures.

Diabetes mellitus is associated with adverse structural and functional cardiac remodelling in chronic heart failure with reduced ejection fraction.

PubMed

Walker, Andrew Mn; Patel, Peysh A; Rajwani, Adil; Groves, David; Denby, Christine; Kearney, Lorraine; Sapsford, Robert J; Witte, Klaus K; Kearney, Mark T; Cubbon, Richard M

2016-09-01

Diabetes mellitus is associated with an increased risk of death and hospitalisation in patients with chronic heart failure. Better understanding of potential underlying mechanisms may aid the development of diabetes mellitus-specific chronic heart failure therapeutic strategies. Prospective observational cohort study of 628 patients with chronic heart failure associated with left ventricular systolic dysfunction receiving contemporary evidence-based therapy. Indices of cardiac structure and function, along with symptoms and biochemical parameters, were compared in patients with and without diabetes mellitus at study recruitment and 1 year later. Patients with diabetes mellitus (24.2%) experienced higher rates of all-cause [hazard ratio, 2.3 (95% confidence interval, 1.8-3.0)] and chronic heart failure-specific mortality and hospitalisation despite comparable pharmacological and device-based therapies. At study recruitment, patients with diabetes mellitus were more symptomatic, required greater diuretic doses and more frequently had radiologic evidence of pulmonary oedema, despite higher left ventricular ejection fraction. They also exhibited echocardiographic evidence of increased left ventricular wall thickness and pulmonary arterial pressure. Diabetes mellitus was associated with reduced indices of heart rate variability and increased heart rate turbulence. During follow-up, patients with diabetes mellitus experienced less beneficial left ventricular remodelling and greater deterioration in renal function. Diabetes mellitus is associated with features of adverse structural and functional cardiac remodelling in patients with chronic heart failure. © The Author(s) 2016.

Non Destructive 3D X-Ray Imaging of Nano Structures & Composites at Sub-30 NM Resolution, With a Novel Lab Based X-Ray Microscope

DTIC Science & Technology

2006-11-01

NON DESTRUCTIVE 3D X-RAY IMAGING OF NANO STRUCTURES & COMPOSITES AT SUB-30 NM RESOLUTION, WITH A NOVEL LAB BASED X- RAY MICROSCOPE S H Lau...article we describe a 3D x-ray microscope based on a laboratory x-ray source operating at 2.7, 5.4 or 8.0 keV hard x-ray energies. X-ray computed...tomography (XCT) is used to obtain detailed 3D structural information inside optically opaque materials with sub-30 nm resolution. Applications include

Imaging and three-dimensional reconstruction of chemical groups inside a protein complex using atomic force microscopy

NASA Astrophysics Data System (ADS)

Kim, Duckhoe; Sahin, Ozgur

2015-03-01

Scanning probe microscopes can be used to image and chemically characterize surfaces down to the atomic scale. However, the localized tip-sample interactions in scanning probe microscopes limit high-resolution images to the topmost atomic layer of surfaces, and characterizing the inner structures of materials and biomolecules is a challenge for such instruments. Here, we show that an atomic force microscope can be used to image and three-dimensionally reconstruct chemical groups inside a protein complex. We use short single-stranded DNAs as imaging labels that are linked to target regions inside a protein complex, and T-shaped atomic force microscope cantilevers functionalized with complementary probe DNAs allow the labels to be located with sequence specificity and subnanometre resolution. After measuring pairwise distances between labels, we reconstruct the three-dimensional structure formed by the target chemical groups within the protein complex using simple geometric calculations. Experiments with the biotin-streptavidin complex show that the predicted three-dimensional loci of the carboxylic acid groups of biotins are within 2 Å of their respective loci in the corresponding crystal structure, suggesting that scanning probe microscopes could complement existing structural biological techniques in solving structures that are difficult to study due to their size and complexity.

The Homemade Microscope.

ERIC Educational Resources Information Center

Baker, Roger C., Jr.

1991-01-01

Directions for the building of a pocket microscope that will make visible the details of insect structure and living bacteria are described. Background information on the history of microscopes and lenses is provided. The procedures for producing various types of lenses are included. (KR)

Renew or die: The molecular mechanisms of peptidoglycan recycling and antibiotic resistance in Gram-negative pathogens.

PubMed

Domínguez-Gil, Teresa; Molina, Rafael; Alcorlo, Martín; Hermoso, Juan A

2016-09-01

Antimicrobial resistance is one of the most serious health threats. Cell-wall remodeling processes are tightly regulated to warrant bacterial survival and in some cases are directly linked to antibiotic resistance. Remodeling produces cell-wall fragments that are recycled but can also act as messengers for bacterial communication, as effector molecules in immune response and as signaling molecules triggering antibiotic resistance. This review is intended to provide state-of-the-art information about the molecular mechanisms governing this process and gather structural information of the different macromolecular machineries involved in peptidoglycan recycling in Gram-negative bacteria. The growing body of literature on the 3D structures of the corresponding macromolecules reveals an extraordinary complexity. Considering the increasing incidence and widespread emergence of Gram-negative multidrug-resistant pathogens in clinics, structural information on the main actors of the recycling process paves the way for designing novel antibiotics disrupting cellular communication in the recycling-resistance pathway. Copyright © 2016. Published by Elsevier Ltd.

Environmental-stress-induced Chromatin Regulation and its Heritability

PubMed Central

Fang, Lei; Wuptra, Kenly; Chen, Danqi; Li, Hongjie; Huang, Shau-Ku; Jin, Chunyuan; Yokoyama, Kazunari K

2014-01-01

Chromatin is subject to proofreading and repair mechanisms during the process of DNA replication, as well as repair to maintain genetic and epigenetic information and genome stability. The dynamic structure of chromatin modulates various nuclear processes, including transcription and replication, by altering the accessibility of the DNA to regulatory factors. Structural changes in chromatin are affected by the chemical modification of histone proteins and DNA, remodeling of nucleosomes, incorporation of variant histones, noncoding RNAs, and nonhistone DNA-binding proteins. Phenotypic diversity and fidelity can be balanced by controlling stochastic switching of chromatin structure and dynamics in response to the environmental disruptors and endogenous stresses. The dynamic chromatin remodeling can, therefore, serve as a sensor, through which environmental and/or metabolic agents can alter gene expression, leading to global cellular changes involving multiple interactive networks. Furthermore its recent evidence also suggests that the epigenetic changes are heritable during the development. This review will discuss the environmental sensing system for chromatin regulation and genetic and epigenetic controls from developmental perspectives. PMID:25045581

Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease.

PubMed

Chavassieux, P; Seeman, E; Delmas, P D

2007-04-01

Minimal trauma fractures in bone diseases are the result of bone fragility. Rather than considering bone fragility as being the result of a reduced amount of bone, we recognize that bone fragility is the result of changes in the material and structural properties of bone. A better understanding of the contribution of each component of the material composition and structure and how these interact to maintain whole bone strength is obtained by the study of metabolic bone diseases. Disorders of collagen (osteogenesis imperfecta and Paget's disease of bone), mineral content, composition and distribution (fluorosis and osteomalacia); diseases of high remodeling (postmenopausal osteoporosis, hyperparathyroidism, and hyperthyroidism) and low remodeling (osteopetrosis, pycnodysostosis); and other diseases (idiopathic male osteoporosis, corticosteroid-induced osteoporosis) produce abnormalities in the material composition and structure that lead to bone fragility. Observations in patients and in animal models provide insights on the biomechanical consequences of these illnesses and the nature of the qualities of bone that determine its strength.

In vivo Quantification of the Structural Changes of Collagens in a Melanoma Microenvironment with Second and Third Harmonic Generation Microscopy

NASA Astrophysics Data System (ADS)

Wu, Pei-Chun; Hsieh, Tsung-Yuan; Tsai, Zen-Uong; Liu, Tzu-Ming

2015-03-01

Using in vivo second harmonic generation (SHG) and third harmonic generation (THG) microscopies, we tracked the course of collagen remodeling over time in the same melanoma microenvironment within an individual mouse. The corresponding structural and morphological changes were quantitatively analyzed without labeling using an orientation index (OI), the gray level co-occurrence matrix (GLCM) method, and the intensity ratio of THG to SHG (RTHG/SHG). In the early stage of melanoma development, we found that collagen fibers adjacent to a melanoma have increased OI values and SHG intensities. In the late stages, these collagen networks have more directionality and less homogeneity. The corresponding GLCM traces showed oscillation features and the sum of squared fluctuation VarGLCM increased with the tumor sizes. In addition, the THG intensities of the extracellular matrices increased, indicating an enhanced optical inhomogeneity. Multiplying OI, VarGLCM, and RTHG/SHG together, the combinational collagen remodeling (CR) index at 4 weeks post melanoma implantation showed a 400-times higher value than normal ones. These results validate that our quantitative indices of SHG and THG microscopies are sensitive enough to diagnose the collagen remodeling in vivo. We believe these indices have the potential to help the diagnosis of skin cancers in clinical practice.

Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit.

PubMed

Bucchieri, Fabio; Pitruzzella, Alessandro; Fucarino, Alberto; Gammazza, Antonella Marino; Bavisotto, Celeste Caruso; Marcianò, Vito; Cajozzo, Massimo; Lo Iacono, Giorgio; Marchese, Roberto; Zummo, Giovanni; Holgate, Stephen T; Davies, Donna E

2017-03-01

Epithelial-mesenchymal communication plays a key role in tissue homeostasis and abnormal signaling contributes to chronic airways disease such as COPD. Most in vitro models are limited in complexity and poorly represent this epithelial-mesenchymal trophic unit. We postulated that cellular outgrowth from bronchial tissue would enable development of a mucosal structure that recapitulates better in vivo tissue architecture. Bronchial tissue was embedded in Matrigel and outgrowth cultures monitored using time-lapse microscopy, electrical resistance, light and electron microscopy. Cultures were challenged repetitively with cigarette smoke extract (CSE). The outgrowths formed as a multicellular sheet with motile cilia becoming evident as the Matrigel was remodeled to provide an air interface; cultures were viable for more than one year. Immunofluorescence and electron microscopy (EM) identified an upper layer of mucociliary epithelium and a lower layer of highly organized extracellular matrix (ECM) interspersed with fibroblastic cells separated by a basement membrane. EM analysis of the mucosal construct after repetitive exposure to CSE revealed epithelial damage, loss of cilia, and ECM remodeling, as occurs in vivo. We have developed a robust bronchial mucosal model. The structural changes observed following CSE exposure suggest the model should have utility for drug discovery and preclinical testing, especially those targeting airway remodeling.

In vivo Quantification of the Structural Changes of Collagens in a Melanoma Microenvironment with Second and Third Harmonic Generation Microscopy

PubMed Central

Wu, Pei-Chun; Hsieh, Tsung-Yuan; Tsai, Zen-Uong; Liu, Tzu-Ming

2015-01-01

Using in vivo second harmonic generation (SHG) and third harmonic generation (THG) microscopies, we tracked the course of collagen remodeling over time in the same melanoma microenvironment within an individual mouse. The corresponding structural and morphological changes were quantitatively analyzed without labeling using an orientation index (OI), the gray level co-occurrence matrix (GLCM) method, and the intensity ratio of THG to SHG (RTHG/SHG). In the early stage of melanoma development, we found that collagen fibers adjacent to a melanoma have increased OI values and SHG intensities. In the late stages, these collagen networks have more directionality and less homogeneity. The corresponding GLCM traces showed oscillation features and the sum of squared fluctuation VarGLCM increased with the tumor sizes. In addition, the THG intensities of the extracellular matrices increased, indicating an enhanced optical inhomogeneity. Multiplying OI, VarGLCM, and RTHG/SHG together, the combinational collagen remodeling (CR) index at 4 weeks post melanoma implantation showed a 400-times higher value than normal ones. These results validate that our quantitative indices of SHG and THG microscopies are sensitive enough to diagnose the collagen remodeling in vivo. We believe these indices have the potential to help the diagnosis of skin cancers in clinical practice. PMID:25748390

Confocal microscopy for automatic measurement of the density and distance between elastin fibers of histologic preparations of normotensive and hypertensive patients

NASA Astrophysics Data System (ADS)

Vieira, G.; Ferro, D. P.; Adam, R. L.; de Thomaz, A. A.; Cesar, C. L.; Metze, K.

2010-02-01

Elastic fibers are essential components of the human aorta, and there is an association between elastin fibers remodeling and several diseases. Hypertension is one such example of a disease leading to elastin fibers remodeling. These fibers can be easily seen in eosin-hematoxilin (HE) stained histologic sections when observed by UV-excited fluorescence microscopy or by a much more precise Laser Scanning Confocal Microscope (LSCM). In order to study the effect of the hypertension on the elastin fibers pattern we developed an automatic system (software and hardware) to count the number of elastin fibers and to measure the distance between them in a LSCM and used it compare the statistical distribution of the distance between these fibers in normotensive and hypertensive patients. The full image of the whole sample (2 or 3mm long) was composed by several 220×220μm frames with 512×512 pixels. The software counters fiber and distance between fibers. We compared the elastic fiber texture in routinely HE-stained histologic slides of the aorta ascendens in 24 normotensive and 30 hypertensive adult patients of both sexes and of similar age from our autopsy files. Our results show that the average number of fibers is the same for both cases but the distance between the fibers are larger for hypertensive patients than for normotensive ones.

Cell remodeling and subtilase gene expression in the actinorhizal plant Discaria trinervis highlight host orchestration of intercellular Frankia colonization.

PubMed

Fournier, Joëlle; Imanishi, Leandro; Chabaud, Mireille; Abdou-Pavy, Iltaf; Genre, Andrea; Brichet, Lukas; Lascano, Hernán Ramiro; Muñoz, Nacira; Vayssières, Alice; Pirolles, Elodie; Brottier, Laurent; Gherbi, Hassen; Hocher, Valérie; Svistoonoff, Sergio; Barker, David G; Wall, Luis G

2018-05-23

Nitrogen-fixing filamentous Frankia colonize the root tissues of its actinorhizal host Discaria trinervis via an exclusively intercellular pathway. Here we present studies aimed at uncovering mechanisms associated with this little-researched mode of root entry, and in particular the extent to which the host plant is an active partner during this process. Detailed characterization of the expression patterns of infection-associated actinorhizal host genes has provided valuable tools to identify intercellular infection sites, thus allowing in vivo confocal microscopic studies of the early stages of Frankia colonization. The subtilisin-like serine protease gene Dt12, as well as its Casuarina glauca homolog Cg12, are specifically expressed at sites of Frankia intercellular colonization of D. trinervis outer root tissues. This is accompanied by nucleo-cytoplasmic reorganization in the adjacent host cells and major remodeling of the intercellular apoplastic compartment. These findings lead us to propose that the actinorhizal host plays a major role in modifying both the size and composition of the intercellular apoplast in order to accommodate the filamentous microsymbiont. The implications of these findings are discussed in the light of the analogies that can be made with the orchestrating role of host legumes during intracellular root hair colonization by nitrogen-fixing rhizobia. © 2018 The Authors New Phytologist © 2018 New Phytologist Trust.

Kinetics and tissue repair process following fractional bipolar radiofrequency treatment.

PubMed

Kokolakis, G; von Eichel, L; Ulrich, M; Lademann, J; Zuberbier, T; Hofmann, M A

2018-05-15

Fractionated radiofrequency (RF) tissue tightening is an alternative method to fractionated laser treatment of skin wrinkling, laxity and acne scars, with reduced risk of scarring or persistent pigmentation. The aim of this study was to evaluate and quantify the wound healing process after RF treatment. 12 patients were treated with a 64-pin fractional bipolar RF device with 60 mJ/pin applied energy. Confocal laser scanning microscopy (CLSM) examination was performed on day 1, day 2, day 7 and day 14 after treatment. Clinical wound healing process was measured and expressed as a percentage. All patients developed erythema, mild edema and crusts at the treated areas. Two weeks after treatment clinical symptoms resolved. During ablation patients reported moderate pain. Directly after ablation microscopic ablation zones could be detected in CLSM. Measurement of MAZ at epidermis, dermo-epidermal junction and papilary dermis showed a constant diameter until two weeks after treatment. Re-epithelization of the MAZ could be detected already 1 week after treatment. However, 2 weeks after ablation the honeycomb pattern of the epidermis was not yet completely restored. Bipolar fractionated RF treatment demonstrates clinically a rapid wound healing response. The subepidermal remodelling process still ongoing after 14 days, showing new granulation tissue. Therefore, treatment intervals of at least 14 days should be recommended to allow completion of the remodelling process.

The Effects of Kinetic Structure on Knowledge About and Performance of a Psychomotor Skill: Teaching Students to Use the Compound Microscope

ERIC Educational Resources Information Center

Simmons, Ellen Stephanie

1977-01-01

Investigates effects of method of presentation and structure on secondary student's acquisition of knowledge and psychomotor skills in teaching use of the compound microscope. Psychomotor skills and knowledge acquisitions were both found to be directly related to high structure and separated presentations. (SL)

Systems approach to the study of stretch and arrhythmias in right ventricular failure induced in rats by monocrotaline

PubMed Central

Benoist, David; Stones, Rachel; Benson, Alan P.; Fowler, Ewan D.; Drinkhill, Mark J.; Hardy, Matthew E.L.; Saint, David A.; Cazorla, Olivier; Bernus, Olivier; White, Ed

2014-01-01

We demonstrate the synergistic benefits of using multiple technologies to investigate complex multi-scale biological responses. The combination of reductionist and integrative methodologies can reveal novel insights into mechanisms of action by tracking changes of in vivo phenomena to alterations in protein activity (or vice versa). We have applied this approach to electrical and mechanical remodelling in right ventricular failure caused by monocrotaline-induced pulmonary artery hypertension in rats. We show arrhythmogenic T-wave alternans in the ECG of conscious heart failure animals. Optical mapping of isolated hearts revealed discordant action potential duration (APD) alternans. Potential causes of the arrhythmic substrate; structural remodelling and/or steep APD restitution and dispersion were observed, with specific remodelling of the Right Ventricular Outflow Tract. At the myocyte level, [Ca2+]i transient alternans were observed together with decreased activity, gene and protein expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA). Computer simulations of the electrical and structural remodelling suggest both contribute to a less stable substrate. Echocardiography was used to estimate increased wall stress in failure, in vivo. Stretch of intact and skinned single myocytes revealed no effect on the Frank-Starling mechanism in failing myocytes. In isolated hearts acute stretch-induced arrhythmias occurred in all preparations. Significant shortening of the early APD was seen in control but not failing hearts. These observations may be linked to changes in the gene expression of candidate mechanosensitive ion channels (MSCs) TREK-1 and TRPC1/6. Computer simulations incorporating MSCs and changes in ion channels with failure, based on altered gene expression, largely reproduced experimental observations. PMID:25016242

Microdomain-Specific Modulation of L-Type Calcium Channels Leads to Triggered Ventricular Arrhythmia in Heart Failure

PubMed Central

Sanchez-Alonso, Jose L.; Bhargava, Anamika; O’Hara, Thomas; Glukhov, Alexey V.; Schobesberger, Sophie; Bhogal, Navneet; Sikkel, Markus B.; Mansfield, Catherine; Korchev, Yuri E.; Lyon, Alexander R.; Punjabi, Prakash P.; Nikolaev, Viacheslav O.; Trayanova, Natalia A.

2016-01-01

Rationale: Disruption in subcellular targeting of Ca2+ signaling complexes secondary to changes in cardiac myocyte structure may contribute to the pathophysiology of a variety of cardiac diseases, including heart failure (HF) and certain arrhythmias. Objective: To explore microdomain-targeted remodeling of ventricular L-type Ca2+ channels (LTCCs) in HF. Methods and Results: Super-resolution scanning patch-clamp, confocal and fluorescence microscopy were used to explore the distribution of single LTCCs in different membrane microdomains of nonfailing and failing human and rat ventricular myocytes. Disruption of membrane structure in both species led to the redistribution of functional LTCCs from their canonical location in transversal tubules (T-tubules) to the non-native crest of the sarcolemma, where their open probability was dramatically increased (0.034±0.011 versus 0.154±0.027, P<0.001). High open probability was linked to enhance calcium–calmodulin kinase II–mediated phosphorylation in non-native microdomains and resulted in an elevated ICa,L window current, which contributed to the development of early afterdepolarizations. A novel model of LTCC function in HF was developed; after its validation with experimental data, the model was used to ascertain how HF-induced T-tubule loss led to altered LTCC function and early afterdepolarizations. The HF myocyte model was then implemented in a 3-dimensional left ventricle model, demonstrating that such early afterdepolarizations can propagate and initiate reentrant arrhythmias. Conclusions: Microdomain-targeted remodeling of LTCC properties is an important event in pathways that may contribute to ventricular arrhythmogenesis in the settings of HF-associated remodeling. This extends beyond the classical concept of electric remodeling in HF and adds a new dimension to cardiovascular disease. PMID:27572487

Early treatment with losartan effectively ameliorates hypertension and improves vascular remodeling and function in a prehypertensive rat model.

PubMed

He, De-Hua; Lin, Jin-Xiu; Zhang, Liang-Min; Xu, Chang-Sheng; Xie, Qiang

2017-03-15

Pharmacological treatment of prehypertension may ameliorate hypertension and improve vascular structure and function. This study investigated 1) whether early treatment with either losartan or amlodipine at the onset of prehypertension can prevent hypertension and 2) whether losartan and amlodipine equally improve vascular remodeling and function in a rat model of hypertension. Stroke-prone spontaneously hypertensive (SHRSP) rats were administered losartan, amlodipine or saline for 6 or 16weeks at the onset of prehypertension. Wistar-Kyoto rats were used as a control. All groups were observed for 40weeks. Systolic blood pressure was measured using the tail-cuff method. Vascular structure and function were determined by microscopy and vascular ring contractility assays, respectively. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassays. Angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression was measured by western blot. Losartan effectively reduced progression from prehypertension to hypertension as well as vascular remodeling and improved vascular contractility in SHRSP rats. Long-term losartan (16weeks) had greater benefits than short-term (6weeks) treatment. Losartan increased Ang II and decreased Aldo levels in the serum and vessel walls of resistance vessels in a time-dependent manner. Losartan significantly decreased AT1R and increased AT2R vascular expression. Amlodipine had no effect on vascular AT1R and AT2R expression. Losartan administered at the onset of prehypertension is more effective than amlodipine in ameliorating hypertension and improving vascular remodeling and function, which is likely mediated by the renin-angiotensin-aldosterone system. Copyright © 2017 Elsevier Inc. All rights reserved.

Real-time Visualization of Tissue Dynamics during Embryonic Development and Malignant Transformation

NASA Astrophysics Data System (ADS)

Yamada, Kenneth

Tissues undergo dramatic changes in organization during embryonic development, as well as during cancer progression and invasion. Recent advances in microscopy now allow us to visualize and track directly the dynamic movements of tissues, their constituent cells, and cellular substructures. This behavior can now be visualized not only in regular tissue culture on flat surfaces (`2D' environments), but also in a variety of 3D environments that may provide physiological cues relevant to understanding dynamics within living organisms. Acquisition of imaging data using various microscopy modalities will provide rich opportunities for determining the roles of physical factors and for computational modeling of complex processes in living tissues. Direct visualization of real-time motility is providing insight into biology spanning multiple spatio-temporal scales. Many cells in our body are known to be in contact with connective tissue and other forms of extracellular matrix. They do so through microscopic cellular adhesions that bind to matrix proteins. In particular, fluorescence microscopy has revealed that cells dynamically probe and bend the matrix at the sites of cell adhesions, and that 3D matrix architecture, stiffness, and elasticity can each regulate migration of the cells. Conversely, cells remodel their local matrix as organs form or tumors invade. Cancer cells can invade tissues using microscopic protrusions that degrade the surrounding matrix; in this case, the local matrix protein concentration is more important for inducing the micro-invasive protrusions than stiffness. On the length scales of tissues, transiently high rates of individual cell movement appear to help establish organ architecture. In fact, isolated cells can self-organize to form tissue structures. In all of these cases, in-depth real-time visualization will ultimately provide the extensive data needed for computer modeling and for testing hypotheses in which physical forces interact closely with cell signaling to form organs or promote tumor invasion.

Simulated Microgravity and Recovery-Induced Remodeling of the Left and Right Ventricle

PubMed Central

Zhong, Guohui; Li, Yuheng; Li, Hongxing; Sun, Weijia; Cao, Dengchao; Li, Jianwei; Zhao, Dingsheng; Song, Jinping; Jin, Xiaoyan; Song, Hailin; Yuan, Xinxin; Wu, Xiaorui; Li, Qi; Xu, Qing; Kan, Guanghan; Cao, Hongqing; Ling, Shukuan; Li, Yingxian

2016-01-01

Physiological adaptations to microgravity involve alterations in cardiovascular systems. These adaptations result in cardiac remodeling and orthostatic hypotension. However, the response of the left ventricle (LV) and right ventricle (RV) following hindlimb unloading (HU) and hindlimb reloading (HR) is not clear and the underlying mechanism remains to be understood. In this study, three groups of mice were subjected to HU by tail suspension for 28 days. Following this, two groups were allowed to recover for 7 or 14 days. The control group was treated equally, with the exception of tail suspension. Echocardiography was performed to detect the structure and function changes of heart. Compared with the control, the HU group of mice showed reduced LV-EF (ejection fraction), and LV-FS (fractional shortening). However, mice that were allowed to recover for 7 days after HU (HR-7d) showed increased LVIDs (systolic LV internal diameter) and LV Vols (systolic LV volume). Mice that recovered for 14 days (HR-14d) returned to the normal state. In comparison, RV-EF and RV-FS didn't recover to the normal conditions till being reloaded for 14 days. Compared with the control, RVIDd (diastolic RV internal diameter), and RV Vold (diastolic RV volume) were reduced in HU group and recovered to the normal conditions in HR-7d and HR-14d groups, in which groups RVIDs (systolic RV internal diameter) and RV Vols (systolic RV volume) were increased. Histological analysis and cardiac remodeling gene expression results indicated that HU induces left and right ventricular remodeling. Western blot demonstrated that the phosphorylation of HDAC4 and ERK1/2 and the ratio of LC3-II / LC3-I, were increased following HU and recovered following HR in both LV and RV, and the phosphorylation of AMPK was inhibited in both LV and RV following HU, but only restored in LV following HR for 14 days. These results indicate that simulated microgravity leads to cardiac remodeling, and the remodeling changes can be reversed. Furthermore, in the early stages of recovery, cardiac remodeling may be intensified. Finally, compared with the LV, the RV is not as easily reversed. Cardiac remodeling pathways, such as, HDAC4, ERK1/2, LC3-II, and AMPK were involved in the process. PMID:27445861

Structural changes in endometrial basal glands during menstruation.

PubMed

Garry, R; Hart, R; Karthigasu, K A; Burke, C

2010-09-01

To prospectively observe the changes occurring in endometrial glandular morphology during menstrual shedding and regeneration. Prospective observational study. The academic gynaecological endoscopy unit of a university teaching hospital. Population Thirteen patients investigated for a variety of benign, non-infective gynaecological disorders during the active bleeding phase of the menstrual cycle. The morphological appearances of concurrent histological and scanning electron microscopic images of endometrium taken at different stages of the active bleeding phase of menstruation were studied and correlated with the simultaneous immunohistochemical expression of the Ki-67 proliferation marker and the CD68 marker of macrophage activity. Change in morphology of endometrial glands at various stages of menstruation. Endometrial glands within the basalis show evidence of apoptosis and associated macrophage activity immediately before and during menstruation. There is subsequent destruction and removal of old secretory glandular epithelial elements, and rapid replacement with new narrow glands lined with small epithelial cells. There is no evidence of mitotic cell division or expression of Ki-67 in the glandular cells during this replacement process, but there is evidence of marked macrophage activity prior to glandular cell loss. Early endometrial epithelial repair after menstruation is not a consequence of mitotic cell division. It occurs without evidence of Ki-67 expression. There is structural evidence of programmed cell death and intense macrophage activity associated with glandular remodelling. Dead epithelial cells are shed from the glands and accumulate within the endometrial cavity to be replaced by new small epithelial cells that appear to arise by differentiation of the surrounding stromal cells. We propose that these stromal cells are endometrial progenitor/stem cells.

pH regulators in invadosomal functioning: proton delivery for matrix tasting.

PubMed

Brisson, Lucie; Reshkin, Stephan J; Goré, Jacques; Roger, Sébastien

2012-01-01

Invadosomes are actin-rich finger-like cellular structures sensing and interacting with the surrounding extracellular matrix (ECM) and involved in its proteolytic remodeling. Invadosomes are structures distinct from other adhesion complexes, and have been identified in normal cells that have to cross tissue barriers to fulfill their function such as leukocytes, osteoclasts and endothelial cells. They also represent features of highly aggressive cancer cells, allowing them to escape from the primary tumor, to invade surrounding tissues and to reach systemic circulation. They are localized to the ventral membrane of cells grown under 2-dimensional conditions and are supposed to be present all around cells grown in 3-dimensional matrices. Indeed invadosomes are key structures in physiological processes such as inflammation and the immune response, bone remodeling, tissue repair, but also in pathological conditions such as osteopetrosis and the development of metastases. Invadosomes are subdivided into podosomes, found in normal cells, and into invadopodia specific for cancer cells. While these two structures exhibit differences in organization, size, number and half-life, they share similarities in molecular composition, participation in cell-matrix adhesion and promoting matrix degradation. A key determinant in invadosomal function is the recruitment and release of proteases, such as matrix metalloproteinases (MMPs), serine proteases and cysteine cathepsins, together with their activation in a tightly controlled and highly acidic microenvironment. Therefore numerous pH regulators such as V-ATPases and Na(+)/H(+) exchangers, are found in invadosomes and are directly involved in their constitution as well as their functioning. This review focuses on the participation of pH regulators in invadosome function in physiological and pathological conditions, with a particular emphasis on ECM remodeling by osteoclasts during bone resorption and by cancer cells. Copyright © 2012 Elsevier GmbH. All rights reserved.

Characterization of mechanical properties of lamellar structure of the aortic wall: Effect of aging.

PubMed

Taghizadeh, Hadi; Tafazzoli-Shadpour, Mohammad

2017-01-01

Arterial wall tissues are sensitive to their mechanical surroundings and remodel their structure and mechanical properties when subjected to mechanical stimuli such as increased arterial pressure. Such remodeling is evident in hypertension and aging. Aging is characterized by stiffening of the artery wall which is assigned to disturbed elastin function and increased collagen content. To better understand and provide new insight on microstructural changes induced by aging, the lamellar model of the aortic media was utilized to characterize and compare wall structure and mechanical behavior of the young and old human thoracic aortic samples. Such model regards arterial media as two sets of alternating concentric layers, namely sheets of elastin and interlamellar layers. Histological and biaxial tests were performed and microstructural features and stress-strain curves of media were evaluated in young and old age groups. Then using optimization algorithms and hyperelastic constitutive equations the stress-strain curves of layers were evaluated for both age groups. Results indicated slight elevation in the volume fraction of interlamellar layer among old subjects most probably due to age related collagen deposition. Aging indicated substantial stiffening of interlamellar layers accompanied by noticeable softening of elastic lamellae. The general significant stiffening of old samples were attributed to both increase of volume fraction of interlamellar layers and earlier recruitment of collagen fibers during load bearing due to functional loss of elastin within wall lamellae. Mechanical characterization of lamellar structure of wall media is beneficial in study of arterial remodeling in response to alternated mechanical environment in aging and clinical conditions through coupling of wall microstructure and mechanical behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.

The β3 Adrenergic Receptor Agonist BRL37344 Exacerbates Atrial Structural Remodeling Through iNOS Uncoupling in Canine Models of Atrial Fibrillation.

PubMed

Wang, Xiaobing; Wang, Ruifeng; Liu, Guangzhong; Dong, Jingmei; Zhao, Guanqi; Tian, Jingpu; Sun, Jiayu; Jia, Xiuyue; Wei, Lin; Wang, Yuping; Li, Weimin

2016-01-01

The role of the β3-adrenergic receptor (β3-AR) agonist BRL37344 in atrial fibrillation (AF) structural remodeling and the underlying mechanisms as a therapeutic target were investigated. Four groups of dogs were evaluated: sham, pacing, β3-AR agonist BRL37344 (β3-AGO), and β3-AR antagonist L748337 (β3-ANT) groups. Dogs in the pacing, β3-AGO and β3-ANT groups were subjected to rapid atrial pacing for four weeks. Atrial structure and function, AF inducibility and duration, atrial myocyte apoptosis and interstitial fibrosis were assessed. Atrial superoxide anions were evaluated by fluorescence microscopy and colorimetric assays. Cardiac nitrate+nitrite levels were used to assess nitric oxide (NO) production. Protein and mRNA expression of β3-AR, neuronal NO synthase (nNOS), inducible NO synthase (iNOS), endothelial NO synthase (eNOS) and guanosine triphosphate cyclohydrolase-1 (GCH-1) as well as tetrahydrobiopterin (BH4) levels were measured. β3-AR was up-regulated in AF. Stimulation of β3-AR significantly increased atrial myocyte apoptosis, fibrosis and atrial dilatation, resulting in increased AF induction and prolonged duration. These effects were attenuated by β3-ANT. Moreover, β3-AGO reduced BH4 and NO production and increased superoxide production, which was inhibited by the specific iNOS inhibitor, 1400w β3-AGO also increased iNOS but decreased eNOS and had no effect on nNOS expression in AF. β3-AR stimulation resulted in atrial structural remodeling by increasing iNOS uncoupling and related oxidative stress. β3-AR up-regulation and iNOS uncoupling might be underlying AF therapeutic targets. © 2016 The Author(s) Published by S. Karger AG, Basel.

VESGEN Mapping of Bioactive Protection against Intestinal Inflammation: Application to Human Spaceflight and ISS Experiments

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, P. A.; Chen, X.; Kelly, C. P.; Reinecker, H. C.

2011-01-01

Challenges to successful space exploration and colonization include adverse physiological reactions to micro gravity and space radiation factors. Constant remodeling of the microvasculature is critical for tissue preservation, wound healing, and recovery after ischemia. Regulation of the vascular system in the intestine is particularly important to enable nutrient absorption while maintaining barrier function and mucosal defense against micro biota. Although tremendous progress has been made in understanding the molecular circuits regulating neovascularization, our knowledge of the adaptations of the vascular system to environmental challenges in the intestine remains incomplete. This is in part because of the lack of methods to observe and quantify the complex processes associated with vascular responses in vivo. Developed by GRC as a mature beta version, pre-release research software, VESsel GENeration Analysis (VESGEN) maps and quantifies the fractal-based complexity of vascular branching for novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and microvascular remodeling. Here we demonstrate that VESGEN can be used to characterize the dynamic vascular responses to acute intestinal inflammation and mucosal recovery from in vivo confocal microscopic 3D image series. We induced transient intestinal inflammation in mice by DSS treatment and investigated whether the ability of the pro biotic yeast Saccharomyces boulardii (Sb) to protect against intestinal inflammation was due to regulation of vascular remodeling. A primary characteristic of inflammation is excessive neovascularization (angiogenesis) resulting in fragile vessels prone to bleeding. Morphological parameters for triplicate specimens revealed that Sb treatment greatly reduced the inflammatory response of vascular networks by an average of 78%. This resulted from Sb inhibition of vascular endothelial growth factor receptor signaling, a major angiogenesis signaling pathway. It needs to be determined whether pro biotic yeast represents a promising approach to GI protection in space. GRC performed only the VESGEN post-testing analysis.

Long working distance interference microscope

DOEpatents

Sinclair, Michael B.; DeBoer, Maarten P.; Smith, Norman F.

2004-04-13

Disclosed is a long working distance interference microscope suitable for three-dimensional imaging and metrology of MEMS devices and test structures on a standard microelectronics probe station. The long working distance of 10-30 mm allows standard probes or probe cards to be used. This enables nanometer-scale 3-D height profiles of MEMS test structures to be acquired across an entire wafer. A well-matched pair of reference/sample objectives is not required, significantly reducing the cost of this microscope, as compared to a Linnik microinterferometer.

Fabrication of large area plasmonic nanoparticle grating structure on silver halide based transmission electron microscope film and its application as a surface enhanced Raman spectroscopy substrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sudheer,, E-mail: sudheer@rrcat.gov.in; Tiwari, P.; Singh, M. N.

The plasmonic responses of silver nanoparticle grating structures of different periods made on silver halide based electron microscope film are investigated. Raster scan of the conventional scanning electron microscope (SEM) is used to carry out electron beam lithography for fabricating the plasmonic nanoparticle grating (PNG) structures. Morphological characterization of the PNG structures, carried out by the SEM and the atomic force microscope, indicates that the depth of the groove decreases with a decrease in the grating period. Elemental characterization performed by the energy dispersive spectroscopy and the x-ray diffraction shows the presence of nanoparticles of silver in the PNG grating.more » The optical characterization of the gratings shows that the localized surface plasmon resonance peak shifts from 366 to 378 nm and broadens with a decrease in grating period from 10 to 2.5 μm. The surface enhanced Raman spectroscopy of the Rhodamine-6G dye coated PNG structure shows the maximum enhancement by two orders of magnitude in comparison to the randomly distributed silver nanoparticles having similar size and shape as the PNG structure.« less

In Situ Imaging of Tissue Remodeling with Collagen Hybridizing Peptides

PubMed Central

2017-01-01

Collagen, the major structural component of nearly all mammalian tissues, undergoes extensive proteolytic remodeling during developmental states and a variety of life-threatening diseases such as cancer, myocardial infarction, and fibrosis. While degraded collagen could be an important marker of tissue damage, it is difficult to detect and target using conventional tools. Here, we show that a designed peptide (collagen hybridizing peptide: CHP), which specifically hybridizes to the degraded, unfolded collagen chains, can be used to image degraded collagen and inform tissue remodeling activity in various tissues: labeled with 5-carboxyfluorescein and biotin, CHPs enabled direct localization and quantification of collagen degradation in isolated tissues within pathologic states ranging from osteoarthritis and myocardial infarction to glomerulonephritis and pulmonary fibrosis, as well as in normal tissues during developmental programs associated with embryonic bone formation and skin aging. The results indicate the general correlation between the level of collagen remodeling and the amount of denatured collagen in tissue and show that the CHP probes can be used across species and collagen types, providing a versatile tool for not only pathology and developmental biology research but also histology-based disease diagnosis, staging, and therapeutic screening. This study lays the foundation for further testing CHP as a targeting moiety for theranostic delivery in various animal models. PMID:28877431

The Core Subunit of A Chromatin-Remodeling Complex, ZmCHB101, Plays Essential Roles in Maize Growth and Development.

PubMed

Yu, Xiaoming; Jiang, Lili; Wu, Rui; Meng, Xinchao; Zhang, Ai; Li, Ning; Xia, Qiong; Qi, Xin; Pang, Jinsong; Xu, Zheng-Yi; Liu, Bao

2016-12-05

ATP-dependent chromatin remodeling complexes play essential roles in the regulation of diverse biological processes by formulating a DNA template that is accessible to the general transcription apparatus. Although the function of chromatin remodelers in plant development has been studied in A. thaliana, how it affects growth and development of major crops (e.g., maize) remains uninvestigated. Combining genetic, genomic and bioinformatic analyses, we show here that the maize core subunit of chromatin remodeling complex, ZmCHB101, plays essential roles in growth and development of maize at both vegetative and reproductive stages. Independent ZmCHB101 RNA interference plant lines displayed abaxially curling leaf phenotype due to increase of bulliform cell numbers, and showed impaired development of tassel and cob. RNA-seq-based transcriptome profiling revealed that ZmCHB101 dictated transcriptional reprogramming of a significant set of genes involved in plant development, photosynthesis, metabolic regulation, stress response and gene expressional regulation. Intriguingly, we found that ZmCHB101 was required for maintaining normal nucleosome density and 45 S rDNA compaction. Our findings suggest that the SWI3 protein, ZmCHB101, plays pivotal roles in maize normal growth and development via regulation of chromatin structure.

High-Resolution Mapping of Changes in Histone-DNA Contacts of Nucleosomes Remodeled by ISW2

PubMed Central

Kassabov, Stefan R.; Henry, Nathalia M.; Zofall, Martin; Tsukiyama, Toshio; Bartholomew, Blaine

2002-01-01

The imitation switch (ISWI) complex from yeast containing the Isw2 and Itc1 proteins was shown to preferentially slide mononucleosomes with as little as 23 bp of linker DNA from the end to the center of DNA. The contacts of unique residues in the histone fold regions of H4, H2B, and H2A with DNA were determined with base pair resolution before and after chromatin remodeling by a site-specific photochemical cross-linking approach. The path of DNA and the conformation of the histone octamer in the nucleosome remodeled or slid by ISW2 were not altered, because after adjustment for the new translational position, the DNA contacts at specific sites in the histone octamer had not been changed. Maintenance of the canonical nucleosome structure after sliding was also demonstrated by DNA photoaffinity labeling of histone proteins at specific sites within the DNA template. In addition, nucleosomal DNA does not become more accessible during ISW2 remodeling, as assayed by restriction endonuclease cutting. ISW2 was also shown to have the novel capability of counteracting transcriptional activators by sliding nucleosomes through Gal4-VP16 bound initially to linker DNA and displacing the activator from DNA. PMID:12370299

Cardiovascular response to prescribed detraining among recreational athletes.

PubMed

Pedlar, Charles R; Brown, Marcel G; Shave, Robert E; Otto, James M; Drane, Aimee; Michaud-Finch, Jennifer; Contursi, Miranda; Wasfy, Meagan M; Hutter, Adolph; Picard, Michael H; Lewis, Gregory D; Baggish, Aaron L

2018-04-01

Exercise-induced cardiac remodeling (EICR) and the attendant myocardial adaptations characteristic of the athlete's heart may regress during periods of exercise reduction or abstinence. The time course and mechanisms underlying this reverse remodeling, specifically the impact of concomitant plasma volume (PV) contraction on cardiac chamber size, remain incompletely understood. We therefore studied recreational runners ( n = 21, age 34 ± 7 yr; 48% male) who completed an 18-wk training program (~7 h/wk) culminating in the 2016 Boston Marathon after which total exercise exposure was confined to <2 h/wk (no single session >1 h) for 8 wk. Cardiac structure and function, exercise capacity, and PV were assessed at peak fitness (10-14 days before) and at 4 wk and 8 wk postmarathon. Mixed linear modeling adjusting for age, sex, V̇o 2peak , and marathon finish time was used to compare data across time points. Physiological detraining was evidenced by serial reductions in treadmill performance. Two distinct phases of myocardial remodeling and hematological adaptation were observed. After 4 wk of detraining, there were significant reductions in PV (Δ -6.0%, P < 0.01), left ventricular (LV) wall thickness (Δ -8.1%, <0.05), LV mass (Δ -10.3%, P < 0.001), and right atrial area (Δ -8.2%, P < 0.001). After 8 wk of detraining, there was a significant reduction in right ventricle chamber size (end-diastolic area Δ = -8.0%, P < 0.05) without further concomitant reductions in PV or LV wall thickness. Abrupt reductions in exercise training stimulus result in a structure-specific time course of reverse cardiac remodeling that occurs largely independently of PV contraction. NEW & NOTEWORTHY Significant reverse cardiac remodeling, previously documented among competitive athletes, extends to recreational runners and occurs with a distinct time course. Initial reductions in plasma volume and left ventricular (LV) mass, driven by reductions in wall thickness, are followed by contraction of the right ventricle. Consistent with data from competitive athletes, LV chamber volumes appear less responsive to detraining and may be a more permanent adaptation to sport.

Electron holography study of magnetization behavior in the writer pole of a perpendicular magnetic recording head by a 1 MV transmission electron microscope.

PubMed

Hirata, Kei; Ishida, Yoichi; Akashi, Tetsuya; Shindo, Daisuke; Tonomura, Akira

2012-01-01

The magnetic domain structure of the writer poles of perpendicular magnetic recording heads was studied using electron holography. Although the domain structure of a 100-nm-thick writer pole could be observed with a 300 kV transmission electron microscope, that of the 250-nm-thick writer pole could not be analyzed due to the limited transmission capability of the instrument. On the other hand, the detailed domain structure of the 250-nm-thick writer pole was successfully analyzed by a 1 MV electron microscope using its high transmission capability. The thickness and material dependency of the domain structure of a writer pole were discussed.

Mars Life? - Microscopic Tubular Structures

NASA Technical Reports Server (NTRS)

1996-01-01

This electron microscope image shows tubular structures of likely Martian origin. These structures are very similar in size and shape to extremely tiny microfossils found in some Earth rocks. This photograph is part of a report by a NASA research team published in the Aug. 16, 1996, issue of the journal Science. A two-year investigation by the team found organic molecules, mineral features characteristic of biological activity and possible microscopic fossils such as these inside of an ancient Martian rock that fell to Earth as a meteorite. The largest possible fossils are less than 1/100th the diameter of a human hair in size while most are ten times smaller.

Diabetes-induced mechanophysiological changes in the small intestine and colon

PubMed Central

Zhao, Mirabella; Liao, Donghua; Zhao, Jingbo

2017-01-01

The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients. PMID:28694926

Cardiac damage in athlete's heart: When the "supernormal" heart fails!

PubMed

Carbone, Andreina; D'Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele

2017-06-26

Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete's blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete's heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded.

Cell migration through connective tissue in 3-D

NASA Astrophysics Data System (ADS)

Fabry, Ben

2008-03-01

A prerequisite for metastasis formation is the ability of tumor cells to invade and migrate through connective tissue. Four key components endow tumor cells with this ability: secretion of matrix-degrading enzymes, firm but temporary adhesion onto connective tissue fibers, contractile force generation, and rapid remodeling of cytoskeletal structures. Cell adhesion, contraction, and cytoskeletal remodeling are biomechanical parameter that can be measured on single cells using a panel of biophysical methods. We use 2-D and 3-D traction microscopy to measure contractile forces; magnetic tweezer microrheology to estimate adhesion strengths, cytoskeletal stiffness and molecular turn-over rates; and nanoscale particle tracking to measure cytoskeletal remodeling. On a wide range of tumor cell lines we could show that cell invasiveness correlates with increased expression of integrin adhesion receptors, increased contractile force generation, and increased speed of cytoskeletal reorganization. Each of those biomechanical parameters, however, varied considerably between cell lines of similar invasivity, suggesting that tumor cells employ multiple invasion strategies that cannot be unambiguously characterized using a single assay.

Structure and membrane remodeling activity of ESCRT-III helical polymers

PubMed Central

McCullough, John; Clippinger, Amy K.; Talledge, Nathaniel; Skowyra, Michael L.; Saunders, Marissa G.; Naismith, Teresa V.; Colf, Leremy A.; Afonine, Pavel; Arthur, Christopher; Sundquist, Wesley I.; Hanson, Phyllis I.; Frost, Adam

2015-01-01

The Endosomal Sorting Complexes Required for Transport (ESCRT) proteins mediate fundamental membrane remodeling events that require stabilizing negative membrane curvature. These include endosomal intralumenal vesicle formation, HIV budding, nuclear envelope closure and cytokinetic abscission. ESCRT-III subunits perform key roles in these processes by changing conformation and polymerizing into membrane-remodeling filaments. Here, we report the 4 Å resolution cryo-EM reconstruction of a one-start, double-stranded helical copolymer composed of two different human ESCRT-III subunits, CHMP1B and IST1. The inner strand comprises “open” CHMP1B subunits that interlock in an elaborate domain-swapped architecture, and is encircled by an outer strand of “closed” IST1 subunits. Unlike other ESCRT-III proteins, CHMP1B and IST1 polymers form external coats on positively-curved membranes in vitro and in vivo. Our analysis suggests how common ESCRT-III filament architectures could stabilize different degrees and directions of membrane curvature. PMID:26634441

Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension.

PubMed

Schiffrin, Ernesto L

2015-12-04

This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.

Third molars and premolars extraction in conventional orthodontics and in treatments based on maxillary bone remodeling with temporary anchorage: indications and care.

PubMed

Consolaro, Alberto

2017-02-01

A bone is an anatomic structure in constant remodeling, with different, mutant and wonderfully inconstant designs. With every new and immediate functional demand, there are changes in cortical thickness, trabecular bone density and also in direction and size of trabeculae. Bones' non-stopping search is for adjusting to the functions induced by forces and movements required by a certain life style. Conventional orthodontic planning or with temporary anchorage based on bone remodeling takes into consideration the spaces that are - or may be - occupied by the teeth, in the formation of a functional and esthetic dental arch for the patient. In case it is necessary to extract a tooth and the options are the third molars, partially or totally unerupted, and teeth that belong to other dental groups, obviousness recommends - due to mouth anatomy and physiology, as well as pathologic reasons - extracting the third molars, due to of the several reasons described in the present study.

Third molars and premolars extraction in conventional orthodontics and in treatments based on maxillary bone remodeling with temporary anchorage: indications and care

PubMed Central

Consolaro, Alberto

2017-01-01

ABSTRACT A bone is an anatomic structure in constant remodeling, with different, mutant and wonderfully inconstant designs. With every new and immediate functional demand, there are changes in cortical thickness, trabecular bone density and also in direction and size of trabeculae. Bones' non-stopping search is for adjusting to the functions induced by forces and movements required by a certain life style. Conventional orthodontic planning or with temporary anchorage based on bone remodeling takes into consideration the spaces that are - or may be - occupied by the teeth, in the formation of a functional and esthetic dental arch for the patient. In case it is necessary to extract a tooth and the options are the third molars, partially or totally unerupted, and teeth that belong to other dental groups, obviousness recommends - due to mouth anatomy and physiology, as well as pathologic reasons - extracting the third molars, due to of the several reasons described in the present study. PMID:28444013

Anti-hypertensive and cardioprotective effects of a novel apitherapy formulation via upregulation of peroxisome proliferator-activated receptor-α and -γ in spontaneous hypertensive rats.

PubMed

Sun, Yanru; Han, Mingfeng; Shen, Zhenhuang; Huang, Haibo; Miao, Xiaoqing

2018-02-01

Ventricular remodeling is associated with many heart diseases, and ventricular remodeling induced by hypertension can be fatal independent of hypertension. In this study, we prepared a novel apitherapy formulation, designated Bao-Yuan-Ling (BYL), which contained propolis, royal jelly, and bee venom, to treat spontaneous hypertensive rats (SHRs). We then evaluated the pharmacology of BYL and the potential mechanisms through which BYL affects hypertension and ventricular remodeling. We found that BYL treatment could reduce blood pressure in SHRs. Thereafter, we found that BYL treatment reduced serum levels of angiotensin II, endothelin 1, and transforming growth factor-β and improved the myocardial structure. Moreover, the results of quantitative real-time polymerase chain reaction indicated that BYL treatment could upregulate the mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. Thus, we could conclude that BYL had hypotensive and cardioprotective effects in SHRs, potentially through improvement of myocardial energy metabolism.

Cardiac damage in athlete’s heart: When the “supernormal” heart fails!

PubMed Central

Carbone, Andreina; D’Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele

2017-01-01

Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete’s blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete’s heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded. PMID:28706583

Matching the Purpose of the General Education Curriculum with the Reality of Its Implementation

ERIC Educational Resources Information Center

Cottrell, Lesley; Cottrell, Scott; Wheatly, Michele; Jungblut, Bernadette; Dooley, Elizabeth A.; DiBartolomeo, Lisa

2015-01-01

This essay examines the current general education curriculum (gec) structure at a large institution where the gec program has been remodeled often to meet student needs. Assessment of this structure has been limited. Faculty and adviser perceptions of the gec's role in the larger curriculum, strengths, areas for improvement, and impact on student…

Smartphone confocal microscopy for imaging cellular structures in human skin in vivo.

PubMed

Freeman, Esther E; Semeere, Aggrey; Osman, Hany; Peterson, Gary; Rajadhyaksha, Milind; González, Salvador; Martin, Jeffery N; Anderson, R Rox; Tearney, Guillermo J; Kang, Dongkyun

2018-04-01

We report development of a low-cost smartphone confocal microscope and its first demonstration of in vivo human skin imaging. The smartphone confocal microscope uses a slit aperture and diffraction grating to conduct two-dimensional confocal imaging without using any beam scanning devices. Lateral and axial resolutions of the smartphone confocal microscope were measured as 2 and 5 µm, respectively. In vivo confocal images of human skin revealed characteristic cellular structures, including spinous and basal keratinocytes and papillary dermis. Results suggest that the smartphone confocal microscope has a potential to examine cellular details in vivo and may help disease diagnosis in resource-poor settings, where conducting standard histopathologic analysis is challenging.

Smartphone confocal microscopy for imaging cellular structures in human skin in vivo

PubMed Central

Freeman, Esther E.; Semeere, Aggrey; Osman, Hany; Peterson, Gary; Rajadhyaksha, Milind; González, Salvador; Martin, Jeffery N.; Anderson, R. Rox; Tearney, Guillermo J.; Kang, Dongkyun

2018-01-01

We report development of a low-cost smartphone confocal microscope and its first demonstration of in vivo human skin imaging. The smartphone confocal microscope uses a slit aperture and diffraction grating to conduct two-dimensional confocal imaging without using any beam scanning devices. Lateral and axial resolutions of the smartphone confocal microscope were measured as 2 and 5 µm, respectively. In vivo confocal images of human skin revealed characteristic cellular structures, including spinous and basal keratinocytes and papillary dermis. Results suggest that the smartphone confocal microscope has a potential to examine cellular details in vivo and may help disease diagnosis in resource-poor settings, where conducting standard histopathologic analysis is challenging. PMID:29675328

Mars Life? - Microscopic Tube-like Structures

NASA Technical Reports Server (NTRS)

1996-01-01

This electron microscope image is a close-up of the center part of photo number S96-12301. While the exact nature of these tube-like structures is not known, one interpretation is that they may be microscopic fossils of primitive, bacteria-like organisms that may have lived on Mars more than 3.6 billion years ago. A two-year investigation by a NASA research team found organic molecules, mineral features characteristic of biological activity and possible microscopic fossils such as these inside of an ancient Martian rock that fell to Earth as a meteorite. The largest possible fossils are less than 1/100th the diameter of a human hair in size while most are ten times smaller.

Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain.

PubMed

Hill, Robert A; Li, Alice M; Grutzendler, Jaime

2018-05-01

Axonal myelin increases neural processing speed and efficiency. It is unknown whether patterns of myelin distribution are fixed or whether myelinating oligodendrocytes are continually generated in adulthood and maintain the capacity for structural remodeling. Using high-resolution, intravital label-free and fluorescence optical imaging in mouse cortex, we demonstrate lifelong oligodendrocyte generation occurring in parallel with structural plasticity of individual myelin internodes. Continuous internode formation occurred on both partially myelinated and unmyelinated axons, and the total myelin coverage along individual axons progressed up to two years of age. After peak myelination, gradual oligodendrocyte death and myelin degeneration in aging were associated with pronounced internode loss and myelin debris accumulation within microglia. Thus, cortical myelin remodeling is protracted throughout life, potentially playing critical roles in neuronal network homeostasis. The gradual loss of internodes and myelin degeneration in aging could contribute significantly to brain pathogenesis.

Rarely at rest

PubMed Central

Hardwick, Steven W.; Luisi, Ben F.

2013-01-01

RNA helicases are compact, machine-like proteins that can harness the energy of nucleoside triphosphate binding and hydrolysis to dynamically remodel RNA structures and protein-RNA complexes. Through such activities, helicases participate in virtually every process associated with the expression of genetic information. Often found as components of multi-enzyme assemblies, RNA helicases facilitate the processivity of RNA degradation, the remodeling of protein interactions during maturation of structured RNA precursors, and fidelity checks of RNA quality. In turn, the assemblies modulate and guide the activities of the helicases. We describe the roles of RNA helicases with a conserved “DExD/H box” sequence motif in representative examples of such machineries from bacteria, archaea and eukaryotes. The recurrent occurrence of such helicases in complex assemblies throughout the course of evolution suggests a common requirement for their activities to meet cellular demands for the dynamic control of RNA metabolism. PMID:23064154

Transcription forms and remodels supercoiling domains unfolding large-scale chromatin structures

PubMed Central

Naughton, Catherine; Avlonitis, Nicolaos; Corless, Samuel; Prendergast, James G.; Mati, Ioulia K.; Eijk, Paul P.; Cockroft, Scott L.; Bradley, Mark; Ylstra, Bauke; Gilbert, Nick

2013-01-01

DNA supercoiling is an inherent consequence of twisting DNA and is critical for regulating gene expression and DNA replication. However, DNA supercoiling at a genomic scale in human cells is uncharacterized. To map supercoiling we used biotinylated-trimethylpsoralen as a DNA structure probe to show the genome is organized into supercoiling domains. Domains are formed and remodeled by RNA polymerase and topoisomerase activities and are flanked by GC-AT boundaries and CTCF binding sites. Under-wound domains are transcriptionally active, enriched in topoisomerase I, “open” chromatin fibers and DNaseI sites, but are depleted of topoisomerase II. Furthermore DNA supercoiling impacts on additional levels of chromatin compaction as under-wound domains are cytologically decondensed, topologically constrained, and decompacted by transcription of short RNAs. We suggest that supercoiling domains create a topological environment that facilitates gene activation providing an evolutionary purpose for clustering genes along chromosomes. PMID:23416946

Mineralocorticoid Receptor Antagonism Prevents Obesity-Induced Cerebral Artery Remodeling and Reduces White Matter Injury in rats.

PubMed

Pires, Paulo Wagner; McClain, Jonathon Lee; Hayoz, Sebastian F; Dorrance, Anne McLaren

2018-05-14

Midlife obesity is a risk factor for dementia development. Obesity has also been linked to hyperaldosteronism, and this can be modeled in rats by high fat (HF) feeding from weaning. Aldosterone, or activation of the mineralocorticoid receptor (MR) causes cerebrovascular injury in lean hypertensive rats. We hypothesized that rats fed a HF diet would show inward middle cerebral artery (MCA) remodeling that could be prevented by MR antagonism. We further proposed that the cerebral artery remodeling would be associated with white mater injury. Three-week-old male Sprague-Dawley rats were fed a HF diet ± the MR antagonist canrenoic acid (Canr) for 17 weeks. Control rats received normal chow (Control NC). MCA structure was assessed by pressure myography. The MCAs from HF fed rats had smaller lumens and thicker walls when compared to arteries from Control NC rats; Canr prevented the MCA remodeling associated with HF feeding. HF feeding increased the mRNA expression of markers of cell proliferation and vascular inflammation in cerebral arteries and Canr treatment prevented this. White mater injury was increased in the rats fed the HF diet and this was reduced by Canr treatment. The expression of doublecortin, a marker of new and immature neurons was reduced in HF fed rats, and MR antagonism normalized this. These data suggest that HF feeding leads to MR dependent remodeling of the MCA and this is associated with markers of dementia development. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Reconstructing a missing link in the evolution of a recently diverged phosphotriesterase by active-site loop remodeling.

PubMed

Afriat-Jurnou, Livnat; Jackson, Colin J; Tawfik, Dan S

2012-08-07

Only decades after the introduction of organophosphate pesticides, bacterial phosphotriesterases (PTEs) have evolved to catalyze their degradation with remarkable efficiency. Their closest known relatives, lactonases, with promiscuous phosphotriasterase activity, dubbed PTE-like lactonases (PLLs), share only 30% sequence identity and also differ in the configuration of their active-site loops. PTE was therefore presumed to have evolved from a yet unknown PLL whose primary activity was the hydrolysis of quorum sensing homoserine lactones (HSLs) (Afriat et al. (2006) Biochemistry 45, 13677-13686). However, how PTEs diverged from this presumed PLL remains a mystery. In this study we investigated loop remodeling as a means of reconstructing a homoserine lactonase ancestor that relates to PTE by few mutational steps. Although, in nature, loop remodeling is a common mechanism of divergence of enzymatic functions, reproducing this process in the laboratory is a challenge. Structural and phylogenetic analyses enabled us to remodel one of PTE's active-site loops into a PLL-like configuration. A deletion in loop 7, combined with an adjacent, highly epistatic, point mutation led to the emergence of an HSLase activity that is undetectable in PTE (k(cat)/K(M) values of up to 2 × 10(4)). The appearance of the HSLase activity was accompanied by only a minor decrease in PTE's paraoxonase activity. This specificity change demonstrates the potential role of bifunctional intermediates in the divergence of new enzymatic functions and highlights the critical contribution of loop remodeling to the rapid divergence of new enzyme functions.

Cardiac CaM Kinase II genes δ and γ contribute to adverse remodeling but redundantly inhibit calcineurin-induced myocardial hypertrophy.

PubMed

Kreusser, Michael M; Lehmann, Lorenz H; Keranov, Stanislav; Hoting, Marc-Oscar; Oehl, Ulrike; Kohlhaas, Michael; Reil, Jan-Christian; Neumann, Kay; Schneider, Michael D; Hill, Joseph A; Dobrev, Dobromir; Maack, Christoph; Maier, Lars S; Gröne, Hermann-Josef; Katus, Hugo A; Olson, Eric N; Backs, Johannes

2014-10-07

Ca(2+)-dependent signaling through CaM Kinase II (CaMKII) and calcineurin was suggested to contribute to adverse cardiac remodeling. However, the relative importance of CaMKII versus calcineurin for adverse cardiac remodeling remained unclear. We generated double-knockout mice (DKO) lacking the 2 cardiac CaMKII genes δ and γ specifically in cardiomyocytes. We show that both CaMKII isoforms contribute redundantly to phosphorylation not only of phospholamban, ryanodine receptor 2, and histone deacetylase 4, but also calcineurin. Under baseline conditions, DKO mice are viable and display neither abnormal Ca(2+) handling nor functional and structural changes. On pathological pressure overload and β-adrenergic stimulation, DKO mice are protected against cardiac dysfunction and interstitial fibrosis. But surprisingly and paradoxically, DKO mice develop cardiac hypertrophy driven by excessive activation of endogenous calcineurin, which is associated with a lack of phosphorylation at the auto-inhibitory calcineurin A site Ser411. Likewise, calcineurin inhibition prevents cardiac hypertrophy in DKO. On exercise performance, DKO mice show an exaggeration of cardiac hypertrophy with increased expression of the calcineurin target gene RCAN1-4 but no signs of adverse cardiac remodeling. We established a mouse model in which CaMKII's activity is specifically and completely abolished. By the use of this model we show that CaMKII induces maladaptive cardiac remodeling while it inhibits calcineurin-dependent hypertrophy. These data suggest inhibition of CaMKII but not calcineurin as a promising approach to attenuate the progression of heart failure. © 2014 American Heart Association, Inc.

Histone octamer trans-transfer: a signature mechanism of ATP-dependent chromatin remodelling unravelled in wheat nuclear extract

PubMed Central

Raut, Vishal V.; Pandey, Shashibhal M.; Sainis, Jayashree K.

2011-01-01

Background and Scope In eukaryotes, chromatin remodelling complexes are shown to be responsible for nucleosome mobility, leading to increased accessibility of DNA for DNA binding proteins. Although the existence of such complexes in plants has been surmised mainly at the genetic level from bioinformatics studies and analysis of mutants, the biochemical existence of such complexes has remained unexplored. Methods Histone H1-depleted donor chromatin was prepared by micrococcal nuclease digestion of wheat nuclei and fractionation by exclusion chromatography. Nuclear extract was partially purified by cellulose phosphate ion exchange chromatography. Histone octamer trans-transfer activity was analysed using the synthetic nucleosome positioning sequence in the absence and presence of ATP and its analogues. ATPase activity was measured as 32Pi released using liquid scintillation counting. Key Results ATP-dependent histone octamer trans-transfer activity, partially purified from wheat nuclei using cellulose phosphate, showed ATP-dependent octamer displacement in trans from the H1-depleted native donor chromatin of wheat to the labelled synthetic nucleosome positioning sequence. It also showed nucleosome-dependent ATPase activity. Substitution of ATP by ATP analogues, namely ATPγS, AMP-PNP and ADP abolished the octamer trans-transfer, indicating the requirement of ATP hydrolysis for this activity. Conclusions ATP-dependent histone octamer transfer in trans is a recognized activity of chromatin remodelling complexes required for chromatin structure dynamics in non-plant species. Our results suggested that wheat nuclei also possess a typical chromatin remodelling activity, similar to that in other eukaryotes. This is the first report on chromatin remodelling activity in vitro from plants. PMID:21896571

Research on the traditional Chinese medicine treating gastrointestinal motility in diabetic rats by improving biomechanical remodeling and neuroendocrine regulation

PubMed Central

Tian, Jiaxing; Li, Min; Zhao, Jingbo; Li, Junling; Liu, Guifang; Zhen, Zhong; Cao, Yang; Gregersen, Hans; Tong, Xiaolin

2017-01-01

Previous studies have demonstrated that TWA, a Chinese herbal medicine, could significantly improve the symptoms of patients with diabetic gastrointestinal dysfunction. However, the specific mechanism of regulating intestinal peristalsis has not been found. This study aimed to discover TWA’s therapeutic mechanism for regulating intestinal motility. The intestinal propulsion rate of diabetic rats was significantly increased after treatment with TWA for 8 weeks. Aiming at the mechanical structure, biomechanical testing indicated that TWA can significantly decrease the no-load intestinal wall thickness, cross-sectional area, and angular spread in a zero-stress state. Notably, intestinal stress-strain curve shifted to the right, which indicated TWA can inhibit intestinal hyperplasia and hardening and improve biomechanical remodeling. Further study of the mechanism revealed that TWA significantly inhibited the expression of AGE in the villi, crypt, and muscle and RAGE in crypt and upregulated the expression of nerve regulator (PSD95, C-kit and SCF). Radioimmunoassay showed TWA treatment decreased levels of serum somatostatin and vasoactive intestinal peptide. Moreover, associations were found between the intestinal propulsion rate with the morphologic and biomechanical remodeling parameters, changes of nerve factors, and endocrine hormones. Morphologic and biomechanical remodeling of the intestinal wall are the pathologic basis of gastrointestinal dysfunction. TWA can benefit intestinal motility by improving biomechanical and morphologic remodeling and by regulating expression of neuroendocrine factors. The results showed that the effect of TWA was dose-dependent, the higher the dose, the greater is the improvement. Thus, traditional Chinese medicine might be a valuable tool for treating diabetic gastrointestinal dysfunction. PMID:28559973

Multiscale molecular dynamics simulations of membrane remodeling by Bin/Amphiphysin/Rvs family proteins

NASA Astrophysics Data System (ADS)

Chun, Chan; Haohua, Wen; Lanyuan, Lu; Jun, Fan

2016-01-01

Membrane curvature is no longer thought of as a passive property of the membrane; rather, it is considered as an active, regulated state that serves various purposes in the cell such as between cells and organelle definition. While transport is usually mediated by tiny membrane bubbles known as vesicles or membrane tubules, such communication requires complex interplay between the lipid bilayers and cytosolic proteins such as members of the Bin/Amphiphysin/Rvs (BAR) superfamily of proteins. With rapid developments in novel experimental techniques, membrane remodeling has become a rapidly emerging new field in recent years. Molecular dynamics (MD) simulations are important tools for obtaining atomistic information regarding the structural and dynamic aspects of biological systems and for understanding the physics-related aspects. The availability of more sophisticated experimental data poses challenges to the theoretical community for developing novel theoretical and computational techniques that can be used to better interpret the experimental results to obtain further functional insights. In this review, we summarize the general mechanisms underlying membrane remodeling controlled or mediated by proteins. While studies combining experiments and molecular dynamics simulations recall existing mechanistic models, concurrently, they extend the role of different BAR domain proteins during membrane remodeling processes. We review these recent findings, focusing on how multiscale molecular dynamics simulations aid in understanding the physical basis of BAR domain proteins, as a representative of membrane-remodeling proteins. Project supported by the National Natural Science Foundation of China (Grant No. 21403182) and the Research Grants Council of Hong Kong, China (Grant No. CityU 21300014).

No-Regrets Remodeling, 2nd Edition

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2013-12-01

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.

Insight into the microscopic structure of an AdS black hole from a thermodynamical phase transition.

PubMed

Wei, Shao-Wen; Liu, Yu-Xiao

2015-09-11

Comparing with an ordinary thermodynamic system, we investigate the possible microscopic structure of a charged anti-de Sitter black hole completely from the thermodynamic viewpoint. The number density of the black hole molecules is introduced to measure the microscopic degrees of freedom of the black hole. We found that the number density suffers a sudden change accompanied by a latent heat when the black hole system crosses the small-large black hole coexistence curve, while when the system passes the critical point, it encounters a second-order phase transition with a vanishing latent heat due to the continuous change of the number density. Moreover, the thermodynamic scalar curvature suggests that there is a weak attractive interaction between two black hole molecules. These phenomena might cast new insight into the underlying microscopic structure of a charged anti-de Sitter black hole.

Orthogonal decomposition of left ventricular remodeling in myocardial infarction

PubMed Central

Zhang, Xingyu; Medrano-Gracia, Pau; Ambale-Venkatesh, Bharath; Bluemke, David A.; Cowan, Brett R; Finn, J. Paul; Kadish, Alan H.; Lee, Daniel C.; Lima, Joao A. C.; Young, Alistair A.; Suinesiaputra, Avan

2017-01-01

Abstract Left ventricular size and shape are important for quantifying cardiac remodeling in response to cardiovascular disease. Geometric remodeling indices have been shown to have prognostic value in predicting adverse events in the clinical literature, but these often describe interrelated shape changes. We developed a novel method for deriving orthogonal remodeling components directly from any (moderately independent) set of clinical remodeling indices. Results: Six clinical remodeling indices (end-diastolic volume index, sphericity, relative wall thickness, ejection fraction, apical conicity, and longitudinal shortening) were evaluated using cardiac magnetic resonance images of 300 patients with myocardial infarction, and 1991 asymptomatic subjects, obtained from the Cardiac Atlas Project. Partial least squares (PLS) regression of left ventricular shape models resulted in remodeling components that were optimally associated with each remodeling index. A Gram–Schmidt orthogonalization process, by which remodeling components were successively removed from the shape space in the order of shape variance explained, resulted in a set of orthonormal remodeling components. Remodeling scores could then be calculated that quantify the amount of each remodeling component present in each case. A one-factor PLS regression led to more decoupling between scores from the different remodeling components across the entire cohort, and zero correlation between clinical indices and subsequent scores. Conclusions: The PLS orthogonal remodeling components had similar power to describe differences between myocardial infarction patients and asymptomatic subjects as principal component analysis, but were better associated with well-understood clinical indices of cardiac remodeling. The data and analyses are available from www.cardiacatlas.org. PMID:28327972

Vertically aligned nanostructure scanning probe microscope tips

DOEpatents

Guillorn, Michael A.; Ilic, Bojan; Melechko, Anatoli V.; Merkulov, Vladimir I.; Lowndes, Douglas H.; Simpson, Michael L.

2006-12-19

Methods and apparatus are described for cantilever structures that include a vertically aligned nanostructure, especially vertically aligned carbon nanofiber scanning probe microscope tips. An apparatus includes a cantilever structure including a substrate including a cantilever body, that optionally includes a doped layer, and a vertically aligned nanostructure coupled to the cantilever body.

Mars Life? - Microscopic Tube-like Structures

NASA Image and Video Library

1996-08-09

This high-resolution scanning electron microscope image shows an unusual tube-like structural form that is less than 1/100th the width of a human hair in size found in meteorite ALH84001, a meteorite believed to be of Martian origin. http://photojournal.jpl.nasa.gov/catalog/PIA00288

Atmospheric scanning electron microscope observes cells and tissues in open medium through silicon nitride film.

PubMed

Nishiyama, Hidetoshi; Suga, Mitsuo; Ogura, Toshihiko; Maruyama, Yuusuke; Koizumi, Mitsuru; Mio, Kazuhiro; Kitamura, Shinichi; Sato, Chikara

2010-03-01

Direct observation of subcellular structures and their characterization is essential for understanding their physiological functions. To observe them in open environment, we have developed an inverted scanning electron microscope with a detachable, open-culture dish, capable of 8 nm resolution, and combined with a fluorescence microscope quasi-simultaneously observing the same area from the top. For scanning electron microscopy from the bottom, a silicon nitride film window in the base of the dish maintains a vacuum between electron gun and open sample dish while allowing electrons to pass through. Electrons are backscattered from the sample and captured by a detector under the dish. Cells cultured on the open dish can be externally manipulated under optical microscopy, fixed, and observed using scanning electron microscopy. Once fine structures have been revealed by scanning electron microscopy, their component proteins may be identified by comparison with separately prepared fluorescence-labeled optical microscopic images of the candidate proteins, with their heavy-metal-labeled or stained ASEM images. Furthermore, cell nuclei in a tissue block stained with platinum-blue were successfully observed without thin-sectioning, which suggests the applicability of this inverted scanning electron microscope to cancer diagnosis. This microscope visualizes mesoscopic-scale structures, and is also applicable to non-bioscience fields including polymer chemistry. (c) 2010 Elsevier Inc. All rights reserved.

Roles of Caveolin-1 in Angiotensin II-Induced Hypertrophy and Inward Remodeling of Cerebral Pial Arterioles.

PubMed

Umesalma, Shaikamjad; Houwen, Frederick Keith; Baumbach, Gary L; Chan, Siu-Lung

2016-03-01

Angiotensin II (Ang II) is a major determinant of inward remodeling and hypertrophy in pial arterioles that may have an important role in stroke during chronic hypertension. Previously, we found that epidermal growth factor receptor is critical in Ang II-mediated hypertrophy that may involve caveolin-1 (Cav-1). In this study, we examined the effects of Cav-1 and matrix metalloproteinase-9 (MMP9) on Ang II-mediated structural changes in pial arterioles. Cav-1-deficient (Cav-1(-/-)), MMP9-deficient (MMP9(-/-)), and wild-type mice were infused with either Ang II (1000 ng/kg per minute) or saline via osmotic minipumps for 28 days (n=6-8 per group). Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of pial arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined histologically in pressurized fixed pial arterioles. Expression of Cav-1, MMP9, phosphorylated epidermal growth factor receptor, and Akt was determined by Western blotting and immunohistochemistry. Deficiency of Cav-1 or MMP9 did not affect Ang II-induced hypertension. Ang II increased the expression of Cav-1, phosphorylated epidermal growth factor receptor, and Akt in wild-type mice, which was attenuated in Cav-1(-/-) mice. Ang II-induced hypertrophy, inward remodeling, and increased MMP9 expression in pial arterioles were prevented in Cav-1(-/-) mice. Ang II-mediated increases in MMP9 expression and inward remodeling, but not hypertrophy, were prevented in MMP9(-/-) mice. In conclusion, Cav-1 is essential in Ang II-mediated inward remodeling and hypertrophy in pial arterioles. Cav-1-induced MMP9 is exclusively involved in inward remodeling, not hypertrophy. Further studies are needed to determine the role of Akt in Ang II-mediated hypertrophy. © 2016 American Heart Association, Inc.

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

PubMed Central

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

2017-01-01

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 through integrin–ligand interactions. Eosinophils express several types of outer membrane integrin, which are responsible for cell–cell and cell–extracellular matrix interactions. In our previous study we demonstrated that asthmatic eosinophils show increased adhesion to ASM cells and it may be important factor contributing to ASM remodeling in asthma. According to these findings, in the present study we investigated the effects of suppression of eosinophil integrin on eosinophil-induced ASM remodeling in asthma. Materials and Methods: Individual combined cell cultures of immortalized human ASM cells and eosinophils from peripheral blood of 22 asthmatic patients and 17 healthy controls were prepared. Eosinophil adhesion was evaluated using eosinophil peroxidase activity assay. Genes expression levels in ASM cells and eosinophils were measured using quantitative real-time PCR. ASM cell proliferation was measured using alamarBlue® solution. Eosinophil integrins were blocked by incubating with Arg-Gly-Asp-Ser peptide. Results: Eosinophils from the asthma group showed increased outer membrane α4β1 and αMβ2 integrin expression, increased adhesion to ASM cells, and overexpression of TGF-β1 compared with eosinophils from the healthy control group. Blockade of eosinophil RGD-binding integrins by Arg-Gly-Asp-Ser peptide significantly reduced adhesion of eosinophils to ASM cells in both groups. Integrin-blocking decreased the effects of eosinophils on TGF-β1, WNT-5a, and extracellular matrix protein gene expression in ASM cells and ASM cell proliferation in both groups. These effects were more pronounced in the asthma group compared with the control group. Conclusion: Suppression of eosinophil-ASM interaction via RGD-binding integrins attenuates eosinophil-induced ASM remodeling in asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT02648074. PMID:28119625

Impact of specific training and competition on myocardial structure and function in different age ranges of male handball players.

PubMed

Agrebi, Brahim; Tkatchuk, Vladimir; Hlila, Nawel; Mouelhi, Emna; Belhani, Ali

2015-01-01

Handball activity involves cardiac changes and demands a mixture of both eccentric and concentric remodeling within the heart. This study seeks to explore heart performance and cardiac remodeling likely to define cardiac parameters which influence specific performance in male handball players across different age ranges. Forty three players, with a regular training and competitive background in handball separated into three groups aged on average 11.78 ± 0.41 for youth players aka "schools", "elite juniors" 15.99 ± 0.81 and "elite adults" 24.46 ± 2.63 years, underwent echocardiography and ECG examinations. Incremental ergocycle and specific field (SFT) tests have also been conducted. With age and regular training and competition, myocardial remodeling in different age ranges exhibit significant differences in dilatation's parameters between "schools" and "juniors" players, such as the end-diastolic diameter (LVEDD) and the end-systolic diameter of the left ventricle (LVESD), the root of aorta (Ao) and left atrial (LA), while significant increase is observed between "juniors" and "adults" players in the interventricular septum (IVS), the posterior wall thicknesses (PWT) and LV mass index. ECG changes are also noted but NS differences were observed in studied parameters. For incremental maximal test, players demonstrate a significant increase in duration and total work between "schools" and "juniors" and, in total work only, between "juniors" and "seniors". The SFT shows improvement in performance which ranged between 26.17 ± 1.83 sec to 31.23 ± 2.34 sec respectively from "seniors" to "schools". The cross-sectional approach used to compare groups with prior hypothesis that there would be differences in exercise performance and cardiac parameters depending on duration of prior handball practice, leads to point out the early cardiac remodeling within the heart as adaptive change. Prevalence of cardiac chamber dilation with less hypertrophy remodeling was found from "schools" to "juniors" while a prevalence of cardiac hypertrophy with less pronounced chamber dilation remodeling was noted later.

Orthogonal decomposition of left ventricular remodeling in myocardial infarction.

PubMed

Zhang, Xingyu; Medrano-Gracia, Pau; Ambale-Venkatesh, Bharath; Bluemke, David A; Cowan, Brett R; Finn, J Paul; Kadish, Alan H; Lee, Daniel C; Lima, Joao A C; Young, Alistair A; Suinesiaputra, Avan

2017-03-01

Left ventricular size and shape are important for quantifying cardiac remodeling in response to cardiovascular disease. Geometric remodeling indices have been shown to have prognostic value in predicting adverse events in the clinical literature, but these often describe interrelated shape changes. We developed a novel method for deriving orthogonal remodeling components directly from any (moderately independent) set of clinical remodeling indices. Six clinical remodeling indices (end-diastolic volume index, sphericity, relative wall thickness, ejection fraction, apical conicity, and longitudinal shortening) were evaluated using cardiac magnetic resonance images of 300 patients with myocardial infarction, and 1991 asymptomatic subjects, obtained from the Cardiac Atlas Project. Partial least squares (PLS) regression of left ventricular shape models resulted in remodeling components that were optimally associated with each remodeling index. A Gram-Schmidt orthogonalization process, by which remodeling components were successively removed from the shape space in the order of shape variance explained, resulted in a set of orthonormal remodeling components. Remodeling scores could then be calculated that quantify the amount of each remodeling component present in each case. A one-factor PLS regression led to more decoupling between scores from the different remodeling components across the entire cohort, and zero correlation between clinical indices and subsequent scores. The PLS orthogonal remodeling components had similar power to describe differences between myocardial infarction patients and asymptomatic subjects as principal component analysis, but were better associated with well-understood clinical indices of cardiac remodeling. The data and analyses are available from www.cardiacatlas.org. © The Author 2017. Published by Oxford University Press.

Quantitative characterization of semiconductor structures with a scanning microwave microscope.

PubMed

Korolyov, S A; Reznik, A N

2018-02-01

In this work, our earlier method for measuring resistance R sh of semiconductor films with a near-field scanning microwave microscope [A. N. Reznik and S. A. Korolyov, J. Appl. Phys. 119, 094504 (2016)] is studied in a 0.1 kΩ/sq < R sh < 15 kΩ/sq range. The method is based on a microscope model in the form of a monopole or dipole antenna interacting with an arbitrary layered structure. The model fitting parameters are determined from the data yielded by calibration measurements on a system of etalon samples. The performance of the method was analyzed experimentally, using strip-probe and coaxial-probe microscopes in the frequency range of 1-3 GHz. For test structures, we used doped GaN films on the Al 2 O 3 substrate and also transistor structures based on the AlGaN/GaN heterojunction and AlGaAs/GaAs/InGaAs/GaAs/AlGaAs quantum well with a conducting channel. The obtained microwave microscope data were compared with the results of measurements by the van der Pauw method. At the first stage of the experiment, the calibration etalons were bulk homogeneous samples with different permittivity/conductivity values. In this case, satisfactory agreement between the microscope and the van der Pauw data was obtained with a strip probe on all tested samples in the entire range of R sh . With a coaxial probe, such accordance was observed only in high-ohmic samples with R sh > 1 kΩ/sq. The use of GaN film structures as a calibration system helped to increase the accuracy of the coaxial-probe-aided measurement of R sh to a level of ∼10%.

Quantitative characterization of semiconductor structures with a scanning microwave microscope

NASA Astrophysics Data System (ADS)

Korolyov, S. A.; Reznik, A. N.

2018-02-01

In this work, our earlier method for measuring resistance Rsh of semiconductor films with a near-field scanning microwave microscope [A. N. Reznik and S. A. Korolyov, J. Appl. Phys. 119, 094504 (2016)] is studied in a 0.1 kΩ/sq < Rsh < 15 kΩ/sq range. The method is based on a microscope model in the form of a monopole or dipole antenna interacting with an arbitrary layered structure. The model fitting parameters are determined from the data yielded by calibration measurements on a system of etalon samples. The performance of the method was analyzed experimentally, using strip-probe and coaxial-probe microscopes in the frequency range of 1-3 GHz. For test structures, we used doped GaN films on the Al2O3 substrate and also transistor structures based on the AlGaN/GaN heterojunction and AlGaAs/GaAs/InGaAs/GaAs/AlGaAs quantum well with a conducting channel. The obtained microwave microscope data were compared with the results of measurements by the van der Pauw method. At the first stage of the experiment, the calibration etalons were bulk homogeneous samples with different permittivity/conductivity values. In this case, satisfactory agreement between the microscope and the van der Pauw data was obtained with a strip probe on all tested samples in the entire range of Rsh. With a coaxial probe, such accordance was observed only in high-ohmic samples with Rsh > 1 kΩ/sq. The use of GaN film structures as a calibration system helped to increase the accuracy of the coaxial-probe-aided measurement of Rsh to a level of ˜10%.

Application of Fourier transform-second-harmonic generation imaging to the rat cervix.

PubMed

Lau, T Y; Sangha, H K; Chien, E K; McFarlin, B L; Wagoner Johnson, A J; Toussaint, K C

2013-07-01

We present the application of Fourier transform-second-harmonic generation (FT-SHG) imaging to evaluate the arrangement of collagen fibers in five nonpregnant rat cervices. Tissue slices from the mid-cervix and near the external orifice of the cervix were analyzed in both two-dimensions (2D) and three-dimensions (3D). We validate that the cervical microstructure can be quantitatively assessed in three dimensions using FT-SHG imaging and observe collagen fibers oriented both in and out-of-plane in the outermost and the innermost layers, which cannot be observed using 2D FT-SHG analysis alone. This approach has the potential to be a clinically applicable method for measuring progressive changes in collagen organization during cervical remodeling in humans. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

Active nematic gels as active relaxing solids

NASA Astrophysics Data System (ADS)

Turzi, Stefano S.

2017-11-01

I propose a continuum theory for active nematic gels, defined as fluids or suspensions of orientable rodlike objects endowed with active dynamics, that is based on symmetry arguments and compatibility with thermodynamics. The starting point is our recent theory that models (passive) nematic liquid crystals as relaxing nematic elastomers. The interplay between viscoelastic response and active dynamics of the microscopic constituents is naturally taken into account. By contrast with standard theories, activity is not introduced as an additional term of the stress tensor, but it is added as an external remodeling force that competes with the passive relaxation dynamics and drags the system out of equilibrium. In a simple one-dimensional channel geometry, we show that the interaction between nonuniform nematic order and activity results in either a spontaneous flow of particles or a self-organization into subchannels flowing in opposite directions.

T-Tubular Electrical Defects Contribute to Blunted β-Adrenergic Response in Heart Failure.

PubMed

Crocini, Claudia; Coppini, Raffaele; Ferrantini, Cecilia; Yan, Ping; Loew, Leslie M; Poggesi, Corrado; Cerbai, Elisabetta; Pavone, Francesco S; Sacconi, Leonardo

2016-09-03

Alterations of the β-adrenergic signalling, structural remodelling, and electrical failure of T-tubules are hallmarks of heart failure (HF). Here, we assess the effect of β-adrenoceptor activation on local Ca(2+) release in electrically coupled and uncoupled T-tubules in ventricular myocytes from HF rats. We employ an ultrafast random access multi-photon (RAMP) microscope to simultaneously record action potentials and Ca(2+) transients from multiple T-tubules in ventricular cardiomyocytes from a HF rat model of coronary ligation compared to sham-operated rats as a control. We confirmed that β-adrenergic stimulation increases the frequency of Ca(2+) sparks, reduces Ca(2+) transient variability, and hastens the decay of Ca(2+) transients: all these effects are similarly exerted by β-adrenergic stimulation in control and HF cardiomyocytes. Conversely, β-adrenergic stimulation in HF cells accelerates a Ca(2+) rise exclusively in the proximity of T-tubules that regularly conduct the action potential. The delayed Ca(2+) rise found at T-tubules that fail to conduct the action potential is instead not affected by β-adrenergic signalling. Taken together, these findings indicate that HF cells globally respond to β-adrenergic stimulation, except at T-tubules that fail to conduct action potentials, where the blunted effect of the β-adrenergic signalling may be directly caused by the lack of electrical activity.

Identifying the cellular mechanisms of symbiont-induced epithelial morphogenesis in the squid-vibrio association

PubMed Central

Koropatnick, Tanya; Goodson, Michael S.; Heath-Heckman, Elizabeth A. C.; McFall-Ngai, Margaret

2014-01-01

The symbiotic association between the Hawaiian bobtail squid Euprymna scolopes and the luminous marine bacterium Vibrio fischeri provides a unique opportunity to study epithelial morphogenesis. Shortly after hatching, the squid host harvests bacteria from the seawater using currents created by two elaborate fields of ciliated epithelia on the surface of the juvenile light organ. After light organ colonization, the symbiont population signals the gradual loss of the ciliated epithelia through apoptosis of the cells, which culminates in the complete regression of these tissues. Whereas aspects of this process have been studied at the morphological, biochemical and molecular levels, no in-depth analysis of the cellular events has been reported. Here we describe the cellular structure of the epithelial field and present evidence that the symbiosis-induced regression occurs in two steps. Using confocal microscopic analyses, we observed an initial epithelial remodeling, which serves to disable the function of the harvesting apparatus, followed by a protracted regression involving actin rearrangements and epithelial cell extrusion. We identified a metal-dependent gelatinolytic activity in the symbiont-induced morphogenic epithelial fields, suggesting the involvement of Zn-dependent matrix metalloproteinase(s) (MMP) in light organ morphogenesis. These data show that the bacterial symbionts not only induce apoptosis of the field, but also change the form, function and biochemistry of the cells as part of the morphogenic program. PMID:24648207

Identifying the cellular mechanisms of symbiont-induced epithelial morphogenesis in the squid-Vibrio association.

PubMed

Koropatnick, Tanya; Goodson, Michael S; Heath-Heckman, Elizabeth A C; McFall-Ngai, Margaret

2014-02-01

The symbiotic association between the Hawaiian bobtail squid Euprymna scolopes and the luminous marine bacterium Vibrio fischeri provides a unique opportunity to study epithelial morphogenesis. Shortly after hatching, the squid host harvests bacteria from the seawater using currents created by two elaborate fields of ciliated epithelia on the surface of the juvenile light organ. After light organ colonization, the symbiont population signals the gradual loss of the ciliated epithelia through apoptosis of the cells, which culminates in the complete regression of these tissues. Whereas aspects of this process have been studied at the morphological, biochemical, and molecular levels, no in-depth analysis of the cellular events has been reported. Here we describe the cellular structure of the epithelial field and present evidence that the symbiosis-induced regression occurs in two steps. Using confocal microscopic analyses, we observed an initial epithelial remodeling, which serves to disable the function of the harvesting apparatus, followed by a protracted regression involving actin rearrangements and epithelial cell extrusion. We identified a metal-dependent gelatinolytic activity in the symbiont-induced morphogenic epithelial fields, suggesting the involvement of Zn-dependent matrix metalloproteinase(s) (MMP) in light organ morphogenesis. These data show that the bacterial symbionts not only induce apoptosis of the field, but also change the form, function, and biochemistry of the cells as part of the morphogenic program.

Short-term adaptation and chronic cardiac remodelling to high altitude in lowlander natives and Himalayan Sherpa.

PubMed

Stembridge, Mike; Ainslie, Philip N; Shave, Rob

2015-11-01

What is the topic of this review? At high altitude, the cardiovascular system must adapt in order to meet the metabolic demand for oxygen. This review summarizes recent findings relating to short-term and life-long cardiac adaptation to high altitude in the context of exercise capacity. What advances does it highlight? Both Sherpa and lowlanders exhibit smaller left ventricular volumes at high altitude; however, myocardial relaxation, as evidenced by diastolic untwist, is reduced only in Sherpa, indicating that short-term hypoxia does not impair diastolic relaxation. Potential remodelling of systolic function, as evidenced by lower left ventricular systolic twist in Sherpa, may facilitate the requisite sea-level mechanical reserve required during exercise, although this remains to be confirmed. Both short-term and life-long high-altitude exposure challenge the cardiovascular system to meet the metabolic demand for O2 in a hypoxic environment. As the demand for O2 delivery increases during exercise, the circulatory component of oxygen transport is placed under additional stress. Acute adaptation and chronic remodelling of cardiac structure and function may occur to facilitate O2 delivery in lowlanders during sojourn to high altitude and in permanent highland residents. However, our understanding of cardiac structural and functional adaption in Sherpa remains confined to a higher maximal heart rate, lower pulmonary vascular resistance and no differences in resting cardiac output. Ventricular form and function are intrinsically linked through the left ventricular (LV) mechanics that facilitate efficient ejection, minimize myofibre stress during contraction and aid diastolic recoil. Recent examination of LV mechanics has allowed detailed insight into fundamental cardiac adaptation in high-altitude Sherpa. In this symposium report, we review recent advances in our understanding of LV function in both lowlanders and Sherpa at rest and discuss the potential consequences for exercise capacity. Collectively, data indicate chronic structural ventricular adaptation, with adult Sherpa having smaller absolute and relative LV size. Consistent with structural remodelling, cardiac mechanics also differ in Sherpa when compared with lowlanders at high altitude. These differences are characterized by a reduction in resting systolic deformation and slower diastolic untwisting, a surrogate of relaxation. These changes may reflect a functional cardiac adaptation that affords Sherpa the same mechanical reserve seen in lowlanders at sea level, which is absent when they ascend to high altitude. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Examination of silicon solar cells by means of the Scanning Laser Acoustic Microscope (SLAM)

NASA Technical Reports Server (NTRS)

Vorres, C.; Yuhas, D. E.

1981-01-01

The Scanning Laser Acoustic Microscope produces images of internal structure in materials. The acoustic microscope is an imaging system based upon acoustic rather than electromagnetic waves. Variations in the elastic propertis are primarily responsible for structure visualized in acoustic micrographs. The instrument used in these investigations is the SONOMICROSCOPE 100 which can be operated at ultrasonic frequencies of from 30 MHz to 500 MHz. The examination of the silicon solar cells was made at 100 MHz. Data are presented in the form of photomicrographs.

Visualizing Morphological Changes of Abscission Zone Cells in Arabidopsis by Scanning Electron Microscope.

PubMed

Shi, Chun-Lin; Butenko, Melinka A

2018-01-01

Scanning electron microscope (SEM) is a type of electron microscope which produces detailed images of surface structures. It has been widely used in plants and animals to study cellular structures. Here, we describe a detailed protocol to prepare samples of floral abscission zones (AZs) for SEM, as well as further image analysis. We show that it is a powerful tool to detect morphologic changes at the cellular level during the course of abscission in wild-type plants and to establish the details of phenotypic alteration in abscission mutants.

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

PubMed Central

2010-01-01

Background Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Methods Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Results Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p < 0.05) expression in ONJ-adjacent periodontal tissue. ONJ tissue also exhibited decreased relative gene expression for Msx-1 (p < 0.03) and RANKL (p < 0.03) and increased BMP-2/4 expression (p < 0.02) compared to control. Conclusions These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue. PMID:20942943

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features.

PubMed

Wehrhan, Falk; Hyckel, Peter; Ries, Jutta; Stockmann, Phillip; Nkenke, Emeka; Schlegel, Karl A; Neukam, Friedrich W; Amann, Kerstin

2010-10-13

Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p < 0.05) expression in ONJ-adjacent periodontal tissue. ONJ tissue also exhibited decreased relative gene expression for Msx-1 (p < 0.03) and RANKL (p < 0.03) and increased BMP-2/4 expression (p < 0.02) compared to control. These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue.

Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption

PubMed Central

Wimer, H.F.; Yamada, S.S.; Yang, T.; Holmbeck, K.; Foster, B.L.

2016-01-01

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a transmembrane zinc-endopeptidase that breaks down extracellular matrix components, including several collagens, during tissue development and physiological remodeling. MT1-MMP-deficient mice (MT1-MMP−/−) feature severe defects in connective tissues, such as impaired growth, osteopenia, fibrosis, and conspicuous loss of molar tooth eruption and root formation. In order to define the functions of MT1-MMP during root formation and tooth eruption, we analyzed the development of teeth and surrounding tissues in the absence of MT1-MMP. In situ hybridization showed that MT1-MMP was widely expressed in cells associated with teeth and surrounding connective tissues during development. Multiple defects in dentoalveolar tissues were associated with loss of MT1-MMP. Root formation was inhibited by defective structure and function of Hertwig's epithelial root sheath (HERS). However, no defect was found in creation of the eruption pathway, suggesting that tooth eruption was hampered by lack of alveolar bone modeling/remodeling coincident with reduced periodontal ligament (PDL) formation and integration with the alveolar bone. Additionally, we identified a significant defect in dentin formation and mineralization associated with the loss of MT1-MMP. To segregate these multiple defects and trace their cellular origin, conditional ablation of MT1-MMP was performed in epithelia and mesenchyme. Mice featuring selective loss of MT1-MMP activity in the epithelium were indistinguishable from wild type mice, and importantly, featured a normal HERS structure and molar eruption. In contrast, selective knock-out of MT1-MMP in Osterix-expressing mesenchymal cells, including osteoblasts and odontoblasts, recapitulated major defects from the global knock-out including altered HERS structure, short roots, defective dentin formation and mineralization, and reduced alveolar bone formation, although molars were able to erupt. These data indicate that MT1-MMP activity in the dental mesenchyme, and not in epithelial-derived HERS, is essential for proper tooth root formation and eruption. In summary, our studies point to an indispensable role for MT1-MMP-mediated matrix remodeling in tooth eruption through effects on bone formation, soft tissue remodeling and organization of the follicle/PDL region. PMID:26780723

Functional Differentiation of SWI/SNF Remodelers in Transcription and Cell Cycle Control▿ †

PubMed Central

Moshkin, Yuri M.; Mohrmann, Lisette; van Ijcken, Wilfred F. J.; Verrijzer, C. Peter

2007-01-01

Drosophila BAP and PBAP represent two evolutionarily conserved subclasses of SWI/SNF chromatin remodelers. The two complexes share the same core subunits, including the BRM ATPase, but differ in a few signature subunits: OSA defines BAP, whereas Polybromo (PB) and BAP170 specify PBAP. Here, we present a comprehensive structure-function analysis of BAP and PBAP. An RNA interference knockdown survey revealed that the core subunits BRM and MOR are critical for the structural integrity of both complexes. Whole-genome expression profiling suggested that the SWI/SNF core complex is largely dysfunctional in cells. Regulation of the majority of target genes required the signature subunit OSA, PB, or BAP170, suggesting that SWI/SNF remodelers function mostly as holoenzymes. BAP and PBAP execute similar, independent, or antagonistic functions in transcription control and appear to direct mostly distinct biological processes. BAP, but not PBAP, is required for cell cycle progression through mitosis. Because in yeast the PBAP-homologous complex, RSC, controls cell cycle progression, our finding reveals a functional switch during evolution. BAP mediates G2/M transition through direct regulation of string/cdc25. Its signature subunit, OSA, is required for directing BAP to the string/cdc25 promoter. Our results suggest that the core subunits play architectural and enzymatic roles but that the signature subunits determine most of the functional specificity of SWI/SNF holoenzymes in general gene control. PMID:17101803

Comprehensive optical and data management infrastructure for high-throughput light-sheet microscopy of whole mouse brains.

PubMed

Müllenbroich, M Caroline; Silvestri, Ludovico; Onofri, Leonardo; Costantini, Irene; Hoff, Marcel Van't; Sacconi, Leonardo; Iannello, Giulio; Pavone, Francesco S

2015-10-01

Comprehensive mapping and quantification of neuronal projections in the central nervous system requires high-throughput imaging of large volumes with microscopic resolution. To this end, we have developed a confocal light-sheet microscope that has been optimized for three-dimensional (3-D) imaging of structurally intact clarified whole-mount mouse brains. We describe the optical and electromechanical arrangement of the microscope and give details on the organization of the microscope management software. The software orchestrates all components of the microscope, coordinates critical timing and synchronization, and has been written in a versatile and modular structure using the LabVIEW language. It can easily be adapted and integrated to other microscope systems and has been made freely available to the light-sheet community. The tremendous amount of data routinely generated by light-sheet microscopy further requires novel strategies for data handling and storage. To complete the full imaging pipeline of our high-throughput microscope, we further elaborate on big data management from streaming of raw images up to stitching of 3-D datasets. The mesoscale neuroanatomy imaged at micron-scale resolution in those datasets allows characterization and quantification of neuronal projections in unsectioned mouse brains.

Correlative STED and Atomic Force Microscopy on Live Astrocytes Reveals Plasticity of Cytoskeletal Structure and Membrane Physical Properties during Polarized Migration

PubMed Central

Curry, Nathan; Ghézali, Grégory; Kaminski Schierle, Gabriele S.; Rouach, Nathalie; Kaminski, Clemens F.

2017-01-01

The plasticity of the cytoskeleton architecture and membrane properties is important for the establishment of cell polarity, adhesion and migration. Here, we present a method which combines stimulated emission depletion (STED) super-resolution imaging and atomic force microscopy (AFM) to correlate cytoskeletal structural information with membrane physical properties in live astrocytes. Using STED compatible dyes for live cell imaging of the cytoskeleton, and simultaneously mapping the cell surface topology with AFM, we obtain unprecedented detail of highly organized networks of actin and microtubules in astrocytes. Combining mechanical data from AFM with optical imaging of actin and tubulin further reveals links between cytoskeleton organization and membrane properties. Using this methodology we illustrate that scratch-induced migration induces cytoskeleton remodeling. The latter is caused by a polarization of actin and microtubule elements within astroglial cell processes, which correlates strongly with changes in cell stiffness. The method opens new avenues for the dynamic probing of the membrane structural and functional plasticity of living brain cells. It is a powerful tool for providing new insights into mechanisms of cell structural remodeling during physiological or pathological processes, such as brain development or tumorigenesis. PMID:28469559

Structural Investigation of Biological and Semiconductor Nanostructures with Nonlinear Multicontrast Microscopy

NASA Astrophysics Data System (ADS)

Cisek, Richard

Physical and functional properties of advanced nano-composite materials and biological structures are determined by self-organized atoms and molecules into nanostructures and in turn by microscopic organization of the nanostructures into assemblies of higher structural complexity. Therefore, microscopes are indispensable tools for structural investigations at various levels of organization. In this work, novel nonlinear optical microscopy methods were developed to non-invasively study structural organization at the nanoscopic and microscopic levels. Atomic organization of semiconductor nanowires, molecular organization of amylose biocrystallites in starch granules, and microscopic organization of several photosynthetic organisms was elucidated. The structure of ZnSe nanowires, key components in many modern nanodevices, was investigated using polarization harmonic generation microscopy. Based on nonlinear optical properties of the different crystal lattices, zinc blende and wurtzite nanowires were differentiated, and the three-dimensional orientation of the zinc blende nanowires could be found. The structure of starch granules, a model biocrystal, important in food as well as health sciences, was also investigated using polarization harmonic microscopy. The study was combined with ab initio calculations using the crystal structures of amylose A and B, revealing that second harmonic signals originate from the hydroxide and hydrogen bonds in the starch granules. Visualization of several photosynthetic organisms including the green algae, Chlamydomonas reinhardtii, two species of cyanobacteria, Leptolyngbya sp. and Anabaena sp., aggregates of light-harvesting pigment-protein complexes as well as chloroplasts from green plants were also explored, revealing that future nonlinear microscopy applications could include structural studies of cell walls, the Chlamydomonas eyespot, and photosynthetic membranes. In this study, several nonlinear optical microscopy modalities were developed for quantitative structural investigations of nano and micro-sized architectures. Non-invasive extraction of crystallographic information in microscopic samples will have a number of potential benefits, for example, in clinical applications, allowing observations of disease states inside tissues without the need for biopsy. Industrial nanotechnology will benefit from fast determination of nanostructures with nonlinear microscopy that will improve quality of nanodevices.

On the Concept "Microscope": Biology Student Teachers' Cognitive Structure

ERIC Educational Resources Information Center

Kurt, Hakan; Ekici, Gulay; Aktas, Murat; Aksu, Ozlem

2013-01-01

The purpose of the current study is to determine biology student teachers' cognitive structures on the concept of microscope. Qualitative research methodology has been applied in the study. The data were collected from biology student teachers. Free word association test and drawing-writing test were used to collect data. The data collected were…

The Microscope: I--Structure. Health Occupations Education Module.

ERIC Educational Resources Information Center

Temple Univ., Philadelphia, PA. Div. of Vocational Education.

This module on the structure of the microscope is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to the module topic, a list of resources needed, and two learning experiences. Each learning experience contains…

Engagement of Arginine Finger to ATP Triggers Large Conformational Changes in NtrC1 AAA+ ATPase for Remodeling Bacterial RNA Polymerase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Baoyu; Sysoeva, Tatyana A.; Chowdhury, Saikat

The NtrC-like AAA+ ATPases control virulence and other important bacterial activities through delivering mechanical work to {sigma}54-RNA polymerase to activate transcription from {sigma}54-dependent genes. We report the first crystal structure for such an ATPase, NtrC1 of Aquifex aeolicus, in which the catalytic arginine engages the {gamma}-phosphate of ATP. Comparing the new structure with those previously known for apo and ADP-bound states supports a rigid-body displacement model that is consistent with large-scale conformational changes observed by low-resolution methods. First, the arginine finger induces rigid-body roll, extending surface loops above the plane of the ATPase ring to bind {sigma}54. Second, ATP hydrolysismore » permits Pi release and retraction of the arginine with a reversed roll, remodeling {sigma}54-RNAP. This model provides a fresh perspective on how ATPase subunits interact within the ring-ensemble to promote transcription, directing attention to structural changes on the arginine-finger side of an ATP-bound interface.« less

Developing an Energy Performance Modeling Startup Kit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, A.

2012-10-01

In 2011, the NAHB Research Center began the first part of the multi-year effort by assessing the needs and motivations of residential remodelers regarding energy performance remodeling. The scope is multifaceted - all perspectives will be sought related to remodeling firms ranging in size from small-scale, sole proprietor to national. This will allow the Research Center to gain a deeper understanding of the remodeling and energy retrofit business and the needs of contractors when offering energy upgrade services. To determine the gaps and the motivation for energy performance remodeling, the NAHB Research Center conducted (1) an initial series of focusmore » groups with remodelers at the 2011 International Builders' Show, (2) a second series of focus groups with remodelers at the NAHB Research Center in conjunction with the NAHB Spring Board meeting in DC, and (3) quantitative market research with remodelers based on the findings from the focus groups. The goal was threefold, to: Understand the current remodeling industry and the role of energy efficiency; Identify the gaps and barriers to adding energy efficiency into remodeling; and Quantify and prioritize the support needs of professional remodelers to increase sales and projects involving improving home energy efficiency. This report outlines all three of these tasks with remodelers.« less

[Remote Slit Lamp Microscope Consultation System Based on Web].

PubMed

Chen, Junfa; Zhuo, Yong; Liu, Zuguo; Chen, Yanping

2015-11-01

To realize the remote operation of the slit lamp microscope for department of ophthalmology consultation, and visual display the real-time status of remote slit lamp microscope, a remote slit lamp microscope consultation system based on B/S structure is designed and implemented. Through framing the slit lamp microscope on the website system, the realtime acquisition and transmission of remote control and image data is realized. The three dimensional model of the slit lamp microscope is established and rendered on the web by using WebGL technology. The practical application results can well show the real-time interactive of the remote consultation system.

Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes.

PubMed

Saffert, Paul; Enenkel, Cordula; Wendler, Petra

2017-01-01

Protein complexes of the Type II AAA+ (ATPases associated with diverse cellular activities) family are typically hexamers of 80-150 kDa protomers that harbor two AAA+ ATPase domains. They form double ring assemblies flanked by associated domains, which can be N-terminal, intercalated or C-terminal to the ATPase domains. Most prominent members of this family include NSF (N-ethyl-maleimide sensitive factor), p97/VCP (valosin-containing protein), the Pex1/Pex6 complex and Hsp104 in eukaryotes and ClpB in bacteria. Tremendous efforts have been undertaken to understand the conformational dynamics of protein remodeling type II AAA+ complexes. A uniform mode of action has not been derived from these works. This review focuses on p97/VCP and the Pex1/6 complex, which both structurally remodel ubiquitinated substrate proteins. P97/VCP plays a role in many processes, including ER- associated protein degradation, and the Pex1/Pex6 complex dislocates and recycles the transport receptor Pex5 from the peroxisomal membrane during peroxisomal protein import. We give an introduction into existing knowledge about the biochemical and cellular activities of the complexes before discussing structural information. We particularly emphasize recent electron microscopy structures of the two AAA+ complexes and summarize their structural differences.

Remote Histology Learning from Static versus Dynamic Microscopic Images

ERIC Educational Resources Information Center

Mione, Sylvia; Valcke, Martin; Cornelissen, Maria

2016-01-01

Histology is the study of microscopic structures in normal tissue sections. Curriculum redesign in medicine has led to a decrease in the use of optical microscopes during practical classes. Other imaging solutions have been implemented to facilitate remote learning. With advancements in imaging technologies, learning material can now be digitized.…

Imaging of Norway spruce early somatic embryos with the ESEM, Cryo-SEM and laser scanning microscope.

PubMed

Neděla, Vilém; Hřib, Jiří; Havel, Ladislav; Hudec, Jiří; Runštuk, Jiří

2016-05-01

This article describes the surface structure of Norway spruce early somatic embryos (ESEs) as a typical culture with asynchronous development. The microstructure of extracellular matrix covering ESEs were observed using the environmental scanning electron microscope as a primary tool and using the scanning electron microscope with cryo attachment and laser electron microscope as a complementary tool allowing our results to be proven independently. The fresh samples were observed in conditions of the air environment of the environmental scanning electron microscope (ESEM) with the pressure from 550Pa to 690Pa and the low temperature of the sample from -18°C to -22°C. The samples were studied using two different types of detector to allow studying either the thin surface structure or material composition. The scanning electron microscope with cryo attachment was used for imaging frozen extracellular matrix microstructure with higher resolution. The combination of both electron microscopy methods was suitable for observation of "native" plant samples, allowing correct evaluation of our results, free of error and artifacts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Matrix metalloproteinases in acute coronary syndromes: current perspectives.

PubMed

Kampoli, Anna-Maria; Tousoulis, Dimitris; Papageorgiou, Nikolaos; Antoniades, Charalambos; Androulakis, Emmanuel; Tsiamis, Eleftherios; Latsios, George; Stefanadis, Christodoulos

2012-01-01

Matrix metalloproteinases (MMPs) are a family of zinc metallo-endopeptidases secreted by cells and are responsible for much of the turnover of matrix components. Several studies have shown that MMPs are involved in all stages of the atherosclerotic process, from the initial lesion to plaque rupture. Recent evidence suggests that MMP activity may facilitate atherosclerosis, plaque destabilization, and platelet aggregation. In the heart, matrix metalloproteinases participate in vascular remodeling, plaque instability, and ventricular remodelling after cardiac injury. The aim of the present article is to review the structure, function, regulation of MMPs and to discuss their potential role in the pathogenesis of acute coronary syndromes, as well as their contribution and usefullness in the setting of the disease.

Plasma tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9: novel indicators of left ventricular remodelling and prognosis after acute myocardial infarction.

PubMed

Kelly, Dominic; Khan, Sohail Q; Thompson, Matt; Cockerill, Gillian; Ng, Leong L; Samani, Nilesh; Squire, Iain B

2008-09-01

Matrix metalloproteinase (MMP) activity is central to the development of left ventricular (LV) remodelling and dysfunction after acute myocardial infarction (AMI). We assessed the relationships with LV structure and function and outcome, of tissue inhibitors of metalloproteinase-1 (TIMP-1) and MMP-9, and compared with N-terminal pro-B-type natriuretic peptide (NTproBNP). We studied 404 patients with AMI. Primary outcome measures were the associations of TIMP-1, MMP-9, and NTproBNP with death or heart failure, and with LV dimensions, function and remodelling (ΔLVEDV, change in LV end-diastolic volume between discharge and follow-up). Cut-off concentrations for prediction of death or heart failure were identified from receiver operator characteristic (ROC) curves. In multivariable analysis, TIMP-1 and NTproBNP had predictive value for LV ejection fraction pre-discharge (TIMP-1 P = 0.023; N-BNP P = 0.007) and at follow-up (TIMP-1 P = 0.001; N-BNP P = 0.003). MMP-9, TIMP-1, and NTproBNP correlated directly with LV volumes. MMP-9 (P = 0.005) and TIMP-1 (P = 0.036), but not NTproBNP, correlated with ΔLVEDV. For the combined endpoint of death or heart failure the area under the ROC curve was 0.640 for MMP-9, 0.799 for NTproBNP and 0.811 for TIMP-1. Patients with TIMP-1 > 135 ng/mL (P < 0.001) or NTproBNP >1472 fmol/mL (P < 0.001) had increased risk of endpoint. Consideration of both NTproBNP and TIMP-1 further improved risk stratification. TIMP-1 and MMP-9 correlate with echocardiographic parameters of LV dysfunction and remodelling after AMI and may identify patients at risk of subsequent LV remodelling and adverse prognosis.

Targeted Injection of a Biocomposite Material Alters Macrophage and Fibroblast Phenotype and Function following Myocardial Infarction: Relation to Left Ventricular Remodeling

PubMed Central

McGarvey, Jeremy R.; Pettaway, Sara; Shuman, James A.; Novack, Craig P.; Zellars, Kia N.; Freels, Parker D.; Echols, Randall L.; Burdick, Jason A.; Gorman, Joseph H.; Gorman, Robert C.

2014-01-01

A treatment target for progressive left ventricular (LV) remodeling prevention following myocardial infarction (MI) is to affect structural changes directly within the MI region. One approach is through targeted injection of biocomposite materials, such as calcium hydroxyapatite microspheres (CHAM), into the MI region. In this study, the effects of CHAM injections upon key cell types responsible for the MI remodeling process, the macrophage and fibroblast, were examined. MI was induced in adult pigs before randomization to CHAM injections (20 targeted 0.1-ml injections within MI region) or saline. At 7 or 21 days post-MI (n = 6/time point per group), cardiac magnetic resonance imaging was performed, followed by macrophage and fibroblast isolation. Isolated macrophage profiles for monocyte chemotactic macrophage inflammatory protein-1 as measured by real-time polymerase chain reaction increased at 7 days post-MI in the CHAM group compared with MI only (16.3 ± 6.6 versus 1.7 ± 0.6 cycle times values, P < 0.05), and were similar by 21 days post-MI. Temporal changes in fibroblast function and smooth muscle actin (SMA) expression relative to referent control (n = 5) occurred with MI. CHAM induced increases in fibroblast proliferation, migration, and SMA expression—indicative of fibroblast transformation. By 21 days, CHAM reduced LV dilation (diastolic volume: 75 ± 2 versus 97 ± 4 ml) and increased function (ejection fraction: 48 ± 2% versus 38 ± 2%) compared with MI only (both P < 0.05). This study identified that effects on macrophage and fibroblast differentiation occurred with injection of biocomposite material within the MI, which translated into reduced adverse LV remodeling. These unique findings demonstrate that biomaterial injections impart biologic effects upon the MI remodeling process over any biophysical effects. PMID:25022514

Late Administration of a Palladium Lipoic Acid Complex (POLY-MVA) Modifies Cardiac Mitochondria but Not Functional or Structural Manifestations of Radiation-Induced Heart Disease in a Rat Model

PubMed Central

Sridharan, Vijayalakshmi; Seawright, John W.; Antonawich, Francis J.; Garnett, Merrill; Cao, Maohua; Singh, Preeti; Boerma, Marjan

2017-01-01

Exposure of the heart to ionizing radiation can cause adverse myocardial remodeling. In small animal models, local heart irradiation causes persistent alterations in cardiac mitochondrial function and swelling. POLY-MVA is a dietary supplement that contains a palladium lipoic acid complex that targets mitochondrial complex I and has been demonstrated to have greater redox potential than lipoic acid alone. POLY-MVA improves mitochondrial function and anti-oxidant enzyme activity in the aged rat heart. In this study, we tested whether POLY-MVA can mitigate cardiac effects of ionizing radiation. Adult male rats were exposed to local heart X rays with a daily dose of 9 Gy for 5 consecutive days. Eighteen weeks after irradiation, POLY-MVA was administered orally at 1 ml/kg bodyweight per day during weekdays, for 6 weeks. Alterations in cardiac function as measured with echocardiography coincided with enhanced mitochondrial swelling, a reduction in mitochondrial expression of complex II, manifestations of adverse remodeling such as a reduction in myocardial microvessel density and an increase in collagen deposition and mast cell numbers. POLY-MVA enhanced left ventricular expression of superoxide dismutase 2, but only in sham-irradiated animals. In irradiated animals, POLY-MVA caused a reduction in markers of inflammatory infiltration, CD2 and CD68. Moreover, POLY-MVA mitigated the effects of radiation on mitochondria. Nonetheless, POLY-MVA did not mitigate adverse cardiac remodeling, suggesting that this tissue remodeling may not be alleviated by altering cardiac mitochondria alone. However, we cannot exclude the possibility that an earlier onset of POLY-MVA administration may have more profound effects on radiation-induced cardiac remodeling. PMID:28231026

Divergent Effects of Losartan and Metoprolol on Cardiac Remodeling, C‐kit+ Cells, Proliferation and Apoptosis in the Left Ventricle after Myocardial Infarction

PubMed Central

Serpi, Raisa; Tolonen, Anna‐Maria; Tenhunen, Olli; Pieviläinen, Oskari; Kubin, Anna‐Maria; Vaskivuo, Tommi; Soini, Ylermi; Kerkelä, Risto; Leskinen, Hanna; Ruskoaho, Heikki

2009-01-01

Abstract There is strong evidence for the use of angiotensin converting enzyme inhibitors and beta‐blockers to reduce morbidity and mortality in patients with myocardial infarction (MI), whereas the effect of angiotensin receptor blockers is less clear. We evaluated the effects of an angiotensin receptor blocker losartan and a beta‐blocker metoprolol on left ventricular (LV) remodeling, c‐kit+ cells, proliferation, fibrosis, apoptosis, and angiogenesis using a model of coronary ligation in rats. Metoprolol treatment for 2 weeks improved LV systolic function. In contrast, losartan triggered deleterious structural remodeling and functional deterioration of LV systolic function, ejection fraction being 41% and fractional shortening 47% lower in losartan group than in controls 2 weeks after MI. The number of c‐kit+ cells as well as expression of Ki‐67 was increased by metoprolol. Losartan‐induced thinning of the anterior wall and ventricular dilation were associated with increased apoptosis and fibrosis, while losartan had no effect on the expression of c‐kit or Ki‐67. Metoprolol or losartan had no effect on microvessel density. These results demonstrate that beta‐blocker treatment attenuated adverse remodeling via c‐kit+ cells and proliferation, whereas angiotensin receptor blocker‐induced worsening of LV systolic function was associated with increased apoptosis and fibrosis in the peri‐infarct region. PMID:20443934

Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model

PubMed Central

Huang, Chun-kai; Chen, Bi-yi; Guo, Ang; Chen, Rong; Zhu, Yan-qi; Kutschke, William; Hong, Jiang; Song, Long-sheng

2016-01-01

Aim: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule (T-tubule) remodeling in left ventricular (LV) failure and thereby providing the therapeutic benefits. Methods: A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding (TAB). One day after TAB, the mice received sildenafil (100 mg·kg−1·d−1, sc) or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes. Results: TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy (R2=0.74, P<0.01) and global LV function (R2=0.47, P<0.01). Conclusion: Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure. PMID:26972492

Gamma Interferon-Induced Guanylate Binding Protein 1 Is a Novel Actin Cytoskeleton Remodeling Factor

PubMed Central

Ostler, Nicole; Britzen-Laurent, Nathalie; Liebl, Andrea; Naschberger, Elisabeth; Lochnit, Günter; Ostler, Markus; Forster, Florian; Kunzelmann, Peter; Ince, Semra; Supper, Verena; Praefcke, Gerrit J. K.; Schubert, Dirk W.; Stockinger, Hannes; Herrmann, Christian

2014-01-01

Gamma interferon (IFN-γ) regulates immune defenses against viruses, intracellular pathogens, and tumors by modulating cell proliferation, migration, invasion, and vesicle trafficking processes. The large GTPase guanylate binding protein 1 (GBP-1) is among the cellular proteins that is the most abundantly induced by IFN-γ and mediates its cell biologic effects. As yet, the molecular mechanisms of action of GBP-1 remain unknown. Applying an interaction proteomics approach, we identified actin as a strong and specific binding partner of GBP-1. Furthermore, GBP-1 colocalized with actin at the subcellular level and was both necessary and sufficient for the extensive remodeling of the fibrous actin structure observed in IFN-γ-exposed cells. These effects were dependent on the oligomerization and the GTPase activity of GBP-1. Purified GBP-1 and actin bound to each other, and this interaction was sufficient to impair the formation of actin filaments in vitro, as demonstrated by atomic force microscopy, dynamic light scattering, and fluorescence-monitored polymerization. Cosedimentation and band shift analyses demonstrated that GBP-1 binds robustly to globular actin and slightly to filamentous actin. This indicated that GBP-1 may induce actin remodeling via globular actin sequestering and/or filament capping. These results establish GBP-1 as a novel member within the family of actin-remodeling proteins specifically mediating IFN-γ-dependent defense strategies. PMID:24190970

Gamma interferon-induced guanylate binding protein 1 is a novel actin cytoskeleton remodeling factor.

PubMed

Ostler, Nicole; Britzen-Laurent, Nathalie; Liebl, Andrea; Naschberger, Elisabeth; Lochnit, Günter; Ostler, Markus; Forster, Florian; Kunzelmann, Peter; Ince, Semra; Supper, Verena; Praefcke, Gerrit J K; Schubert, Dirk W; Stockinger, Hannes; Herrmann, Christian; Stürzl, Michael

2014-01-01

Gamma interferon (IFN-γ) regulates immune defenses against viruses, intracellular pathogens, and tumors by modulating cell proliferation, migration, invasion, and vesicle trafficking processes. The large GTPase guanylate binding protein 1 (GBP-1) is among the cellular proteins that is the most abundantly induced by IFN-γ and mediates its cell biologic effects. As yet, the molecular mechanisms of action of GBP-1 remain unknown. Applying an interaction proteomics approach, we identified actin as a strong and specific binding partner of GBP-1. Furthermore, GBP-1 colocalized with actin at the subcellular level and was both necessary and sufficient for the extensive remodeling of the fibrous actin structure observed in IFN-γ-exposed cells. These effects were dependent on the oligomerization and the GTPase activity of GBP-1. Purified GBP-1 and actin bound to each other, and this interaction was sufficient to impair the formation of actin filaments in vitro, as demonstrated by atomic force microscopy, dynamic light scattering, and fluorescence-monitored polymerization. Cosedimentation and band shift analyses demonstrated that GBP-1 binds robustly to globular actin and slightly to filamentous actin. This indicated that GBP-1 may induce actin remodeling via globular actin sequestering and/or filament capping. These results establish GBP-1 as a novel member within the family of actin-remodeling proteins specifically mediating IFN-γ-dependent defense strategies.

Modeling Endoplasmic Reticulum Network Maintenance in a Plant Cell.

PubMed

Lin, Congping; White, Rhiannon R; Sparkes, Imogen; Ashwin, Peter

2017-07-11

The endoplasmic reticulum (ER) in plant cells forms a highly dynamic network of complex geometry. ER network morphology and dynamics are influenced by a number of biophysical processes, including filament/tubule tension, viscous forces, Brownian diffusion, and interactions with many other organelles and cytoskeletal elements. Previous studies have indicated that ER networks can be thought of as constrained minimal-length networks acted on by a variety of forces that perturb and/or remodel the network. Here, we study two specific biophysical processes involved in remodeling. One is the dynamic relaxation process involving a combination of tubule tension and viscous forces. The other is the rapid creation of cross-connection tubules by direct or indirect interactions with cytoskeletal elements. These processes are able to remodel the ER network: the first reduces network length and complexity whereas the second increases both. Using live cell imaging of ER network dynamics in tobacco leaf epidermal cells, we examine these processes on ER network dynamics. Away from regions of cytoplasmic streaming, we suggest that the dynamic network structure is a balance between the two processes, and we build an integrative model of the two processes for network remodeling. This model produces quantitatively similar ER networks to those observed in experiments. We use the model to explore the effect of parameter variation on statistical properties of the ER network. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling.

PubMed

Wang, Xiaohong; Hu, Qingsong; Nakamura, Yasuhiro; Lee, Joseph; Zhang, Ge; From, Arthur H L; Zhang, Jianyi

2006-07-01

Cardiac stem cell-like populations exist in adult hearts, and their roles in cardiac repair remain to be defined. Sca-1 is an important surface marker for cardiac and other somatic stem cells. We hypothesized that heart-derived Sca-1(+)/CD31(-) cells may play a role in myocardial infarction-induced cardiac repair/remodeling. Mouse heart-derived Sca-1(+)/CD31(-) cells cultured in vitro could be induced to express both endothelial cell and cardiomyocyte markers. Immunofluorescence staining and fluorescence-activated cell sorting analysis indicated that endogenous Sca-1(+)/CD31(-) cells were significantly increased in the mouse heart 7 days after myocardial infarction (MI). Western blotting confirmed elevated Sca-1 protein expression in myocardium 7 days after MI. Transplantation of Sca-1(+)/CD31(-) cells into the acutely infarcted mouse heart attenuated the functional decline and adverse structural remodeling initiated by MI as evidenced by an increased left ventricular (LV) ejection fraction, a decreased LV end-diastolic dimension, a decreased LV end-systolic dimension, a significant increase of myocardial neovascularization, and modest cardiomyocyte regeneration. Attenuation of LV remodeling was accompanied by remarkably improved myocardial bioenergetic characteristics. The beneficial effects of cell transplantation appear to primarily depend on paracrine effects of the transplanted cells on new vessel formation and native cardiomyocyte function. Sca-1(+)/CD31(-) cells may hold therapeutic possibilities with regard to the treatment of ischemic heart disease.

Epigenetic remodelling and dysregulation of DLGAP4 is linked with early-onset cerebellar ataxia

PubMed Central

Minocherhomji, Sheroy; Hansen, Claus; Kim, Hyung-Goo; Mang, Yuan; Bak, Mads; Guldberg, Per; Papadopoulos, Nickolas; Eiberg, Hans; Doh, Gerald Dayebga; Møllgård, Kjeld; Hertz, Jens Michael; Nielsen, Jørgen E.; Ropers, Hans-Hilger; Tümer, Zeynep; Tommerup, Niels; Kalscheuer, Vera M.; Silahtaroglu, Asli

2014-01-01

Genome instability, epigenetic remodelling and structural chromosomal rearrangements are hallmarks of cancer. However, the coordinated epigenetic effects of constitutional chromosomal rearrangements that disrupt genes associated with congenital neurodevelopmental diseases are poorly understood. To understand the genetic–epigenetic interplay at breakpoints of chromosomal translocations disrupting CG-rich loci, we quantified epigenetic modifications at DLGAP4 (SAPAP4), a key post-synaptic density 95 (PSD95) associated gene, truncated by the chromosome translocation t(8;20)(p12;q11.23), co-segregating with cerebellar ataxia in a five-generation family. We report significant epigenetic remodelling of the DLGAP4 locus triggered by the t(8;20)(p12;q11.23) translocation and leading to dysregulation of DLGAP4 expression in affected carriers. Disruption of DLGAP4 results in monoallelic hypermethylation of the truncated DLGAP4 promoter CpG island. This induced hypermethylation is maintained in somatic cells of carriers across several generations in a t(8;20) dependent-manner however, is erased in the germ cells of the translocation carriers. Subsequently, chromatin remodelling of the locus-perturbed monoallelic expression of DLGAP4 mRNAs and non-coding RNAs in haploid cells having the translocation. Our results provide new mechanistic insight into the way a balanced chromosomal rearrangement associated with a neurodevelopmental disorder perturbs allele-specific epigenetic mechanisms at breakpoints leading to the deregulation of the truncated locus. PMID:24986922

Insulin-induced cortical actin remodeling promotes GLUT4 insertion at muscle cell membrane ruffles

PubMed Central

Tong, Peter; Khayat, Zayna A.; Huang, Carol; Patel, Nish; Ueyama, Atsunori; Klip, Amira

2001-01-01

Insulin stimulates glucose uptake by recruiting glucose transporter 4 (GLUT4) from an intracellular compartment to the cell surface; this phenomenon is defective in type 2 diabetes. Here we examine the involvement of actin filaments in GLUT4 translocation and their possible defects in insulin resistance, using L6 myotubes expressing myc-tagged GLUT4. Insulin caused membrane ruffling, a dynamic distortion of the myotube dorsal surface. Fluorescence microscopy and immunogold staining of surface GLUT4myc coupled to backscatter electron microscopy revealed a high density of this protein in membrane ruffles. The t-SNAREs syntaxin4 and SNAP-23 were also abundant in these regions. Below the membrane, GLUT4 and the vesicular protein VAMP2, but not VAMP3, colocalized with the actin structures supporting the membrane ruffles. GLUT4myc externalization and membrane ruffles were reduced by jasplakinolide and by swinholide-A, drugs that affect actin filament stability and prevent actin branching, respectively. Insulin resistance generated by prolonged (24 hours) exposure of myotubes to high glucose and insulin diminished the acute insulin-dependent remodeling of cortical actin and GLUT4myc translocation, reminiscent of the effect of swinholide-A. We propose that GLUT4 vesicle incorporation into the plasma membrane involves insulin-dependent cortical actin remodeling and that defective actin remodeling contributes to insulin resistance. PMID:11489930

Localized tissue mineralization regulated by bone remodelling: A computational approach

PubMed Central

Decco, Oscar; Adams, George; Cook, Richard B.; García Aznar, José Manuel

2017-01-01

Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent–material density curve. Numerical results are discussed pointing to potential clinical applications. PMID:28306746

Density of Stromal Cells and Macrophages Associated With Collagen Remodeling in the Human Cervix in Preterm and Term Birth

PubMed Central

Dubicke, Aurelija; Ekman-Ordeberg, Gunvor; Mazurek, Patricia; Miller, Lindsay; Yellon, Steven M.

2015-01-01

Remodeling of the cervix occurs in advance of labor both at term and at preterm birth. Morphological characteristics associated with remodeling in rodents were assessed in cervix biopsies from women at term (39 weeks’ gestation) and preterm (<33 weeks’ gestation). Collagen I and III messenger RNA and hydroxyproline concentrations declined in cervix biopsies from women in labor at term and preterm compared to that in the cervix from nonlaboring women. Extracellular collagen was more degraded in sections of cervix from women at term, based on optical density of picrosirius red stain, versus that in biopsies from nonpregnant women. However, collagen structure was unchanged in the cervix from women at preterm labor versus the nonpregnant group. As an indication of inflammation, cell nuclei density was decreased in cervix biopsies from pregnant women irrespective of labor compared to the nonpregnant group. Moreover, CD68-stained macrophages increased to an equivalent extent in cervix subepithelium and stroma from groups in labor, both at term and preterm, as well as in women not in labor at term. Evidence for a similar inflammatory process in the remodeled cervix of women at term and preterm birth parallels results in rodent models. Thus, a conserved final common mechanism involving macrophages and inflammation may characterize the transition to a ripe cervix before birth at term and in advance of premature birth. PMID:26608218

Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency.

PubMed

Yang, Xuejun; Zhou, Hua; Qu, Huiyan; Liu, Weifang; Huang, Xiaojin; Shun, Yating; He, Liqun

2014-01-01

To observe the efficacy of Shenxinning Decoction (SXND) in ventricular remodeling in AT1 receptor-knockout (AT1-KO) mice with chronic renal insufficiency (CRI). AT1-KO mice modeled with subtotal (5/6) nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN), serum creatinine (SCr), brain natriuretic peptide (BNP), echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF), collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1) of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice's BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. SXND may antagonize the renin-angiotensin system (RAS) and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1.

The Arabidopsis BRAHMA Chromatin-Remodeling ATPase Is Involved in Repression of Seed Maturation Genes in Leaves1[W][OA

PubMed Central

Tang, Xurong; Hou, Anfu; Babu, Mohan; Nguyen, Vi; Hurtado, Lidia; Lu, Qing; Reyes, Jose C.; Wang, Aiming; Keller, Wilfred A.; Harada, John J.; Tsang, Edward W.T.; Cui, Yuhai

2008-01-01

Synthesis and accumulation of seed storage proteins (SSPs) is an important aspect of the seed maturation program. Genes encoding SSPs are specifically and highly expressed in the seed during maturation. However, the mechanisms that repress the expression of these genes in leaf tissue are not well understood. To gain insight into the repression mechanisms, we performed a genetic screen for mutants that express SSPs in leaves. Here, we show that mutations affecting BRAHMA (BRM), a SNF2 chromatin-remodeling ATPase, cause ectopic expression of a subset of SSPs and other embryogenesis-related genes in leaf tissue. Consistent with the notion that such SNF2-like ATPases form protein complexes in vivo, we observed similar phenotypes for mutations of AtSWI3C, a BRM-interacting partner, and BSH, a SNF5 homolog and essential SWI/SNF subunit. Chromatin immunoprecipitation experiments show that BRM is recruited to the promoters of a number of embryogenesis genes in wild-type leaves, including the 2S genes, expressed in brm leaves. Consistent with its role in nucleosome remodeling, BRM appears to affect the chromatin structure of the At2S2 promoter. Thus, the BRM-containing chromatin-remodeling ATPase complex involved in many aspects of plant development mediates the repression of SSPs in leaf tissue. PMID:18508955

Reprint of: Atmospheric scanning electron microscope observes cells and tissues in open medium through silicon nitride film.

PubMed

Nishiyama, Hidetoshi; Suga, Mitsuo; Ogura, Toshihiko; Maruyama, Yuusuke; Koizumi, Mitsuru; Mio, Kazuhiro; Kitamura, Shinichi; Sato, Chikara

2010-11-01

Direct observation of subcellular structures and their characterization is essential for understanding their physiological functions. To observe them in open environment, we have developed an inverted scanning electron microscope with a detachable, open-culture dish, capable of 8 nm resolution, and combined with a fluorescence microscope quasi-simultaneously observing the same area from the top. For scanning electron microscopy from the bottom, a silicon nitride film window in the base of the dish maintains a vacuum between electron gun and open sample dish while allowing electrons to pass through. Electrons are backscattered from the sample and captured by a detector under the dish. Cells cultured on the open dish can be externally manipulated under optical microscopy, fixed, and observed using scanning electron microscopy. Once fine structures have been revealed by scanning electron microscopy, their component proteins may be identified by comparison with separately prepared fluorescence-labeled optical microscopic images of the candidate proteins, with their heavy-metal-labeled or stained ASEM images. Furthermore, cell nuclei in a tissue block stained with platinum-blue were successfully observed without thin-sectioning, which suggests the applicability of this inverted scanning electron microscope to cancer diagnosis. This microscope visualizes mesoscopic-scale structures, and is also applicable to non-bioscience fields including polymer chemistry. Copyright © 2010 Elsevier Inc. All rights reserved.

Universality of emergent states in diverse physical systems

NASA Astrophysics Data System (ADS)

Guidry, Mike

2017-12-01

Our physics textbooks are dominated by examples of simple weakly-interacting microscopic states, but most of the real world around us is most effectively described in terms of emergent states that have no clear connection to simple textbook states. Emergent states are strongly-correlated and dominated by properties that emerge as a consequence of interactions and are not part of the description of the corresponding weakly-interacting system. This paper proposes a connection of weakly-interacting textbook states and realistic emergent states through fermion dynamical symmetries having fully-microscopic generators of the emergent states. These imply unique truncation of the Hilbert space for the weakly-interacting system to a collective subspace where the emergent states live. Universality arises because the possible symmetries under commutation of generators, which transcend the microscopic structure of the generators, are highly restricted in character and determine the basic structure of the emergent state, with the microscopic structure of the generators influencing emergent state only parametrically. In support of this idea we show explicit evidence that high-temperature superconductors, collective states in heavy atomic nuclei, and graphene quantum Hall states in strong magnetic fields exhibit a near-universal emergent behavior in their microscopically-computed total energy surfaces, even though these systems share essentially nothing in common at the microscopic level and their emergent states are characterized by fundamentally different order parameters.

A Cellular Automata Model of Bone Formation

PubMed Central

Van Scoy, Gabrielle K.; George, Estee L.; Asantewaa, Flora Opoku; Kerns, Lucy; Saunders, Marnie M.; Prieto-Langarica, Alicia

2017-01-01

Bone remodeling is an elegantly orchestrated process by which osteocytes, osteoblasts and osteoclasts function as a syncytium to maintain or modify bone. On the microscopic level, bone consists of cells that create, destroy and monitor the bone matrix. These cells interact in a coordinated manner to maintain a tightly regulated homeostasis. It is this regulation that is responsible for the observed increase in bone gain in the dominant arm of a tennis player and the observed increase in bone loss associated with spaceflight and osteoporosis. The manner in which these cells interact to bring about a change in bone quality and quantity has yet to be fully elucidated. But efforts to understand the multicellular complexity can ultimately lead to eradication of metabolic bone diseases such as osteoporosis and improved implant longevity. Experimentally validated mathematical models that simulate functional activity and offer eventual predictive capabilities offer tremendous potential in understanding multicellular bone remodeling. Here we undertake the initial challenge to develop a mathematical model of bone formation validated with in vitro data obtained from osteoblastic bone cells induced to mineralize and quantified at 26 days of culture. A cellular automata model was constructed to simulate the in vitro characterization. Permutation tests were performed to compare the distribution of the mineralization in the cultures and the distribution of the mineralization in the mathematical models. The results of the permutation test show the distribution of mineralization from the characterization and mathematical model come from the same probability distribution, therefore validating the cellular automata model. PMID:28189632

Patterns of gene expression reveal a temporally orchestrated wound healing response in the injured spinal cord.

PubMed

Velardo, Margaret J; Burger, Corinna; Williams, Philip R; Baker, Henry V; López, M Cecilia; Mareci, Thomas H; White, Todd E; Muzyczka, Nicholas; Reier, Paul J

2004-09-29

Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell survival and neurological integrity via complex and evolving molecular cascades whose interrelationships are not fully understood. The present experiments were designed to: (1) determine potential functional interactions within transcriptional expression profiles obtained after a clinically relevant SCI and (2) test the consistency of transcript expression after SCI in two genetically and immunologically diverse rat strains characterized by differences in T cell competence and associated inflammatory responses. By interrogating Affymetrix U34A rat genome GeneChip microarrays, we defined the transcriptional expression patterns in midcervical contusion lesion sites between 1 and 90 d postinjury of athymic nude (AN) and Sprague Dawley (SD) strains. Stringent statistical analyses detected significant changes in 3638 probe sets, with 80 genes differing between the AN and SD groups. Subsequent detailed functional categorization of these transcripts unveiled an overall tissue remodeling response that was common to both strains. The functionally organized gene profiles were temporally distinct and correlated with repair indices observed microscopically and by magnetic resonance microimaging. Our molecular and anatomical observations have identified a novel, longitudinal perspective of the post-SCI response, namely, that of a highly orchestrated tissue repair and remodeling repertoire with a prominent cutaneous wound healing signature that is conserved between two widely differing rat strains. These results have significant bearing on the continuing development of cellular and pharmacological therapeutics directed at tissue rescue and neuronal regeneration in the injured spinal cord.

Rheological and structural properties of sea cucumber Stichopus japonicus during heat treatment

NASA Astrophysics Data System (ADS)

Gao, Xin; Xue, Dongmei; Zhang, Zhaohui; Xu, Jiachao; Xue, Changhu

2005-07-01

Changes in tissue structure, rheological properties and water content of raw and heated sea cucumber meat were studied. Sea cucumber Stichopus japonicus was heated at 25°C , 70°C and 100°C water for 5 min. The structural changes were observed using a light microscope and the rheological parameters (rupture strength, adhesive strength and deformation) determined using a texture meter. Microscopic photograph revealed that the structural change of heated meat was greater than that of raw meat. The rupture strength, adhesive strength and deformation of raw meat were smaller than those of the heated meat. Meanwhile, rheological parameters showed positive correlation with heating temperature. These changes are mainly caused by thermal denaturation and gelatinization of collagen during heating. These changes were also evidenced in observations using a light microscope and differential scanning calorimetry.

A microscopic study investigating the structure of SnSe surfaces

NASA Astrophysics Data System (ADS)

Kim, Sang-ui; Duong, Anh-Tuan; Cho, Sunglae; Rhim, S. H.; Kim, Jungdae

2016-09-01

SnSe has been widely studied due to its many potential applications that take advantage of its excellent thermoelectric, photovoltaic, and optoelectronic properties. However, experimental investigations into the microscopic structure of SnSe remain largely unexplored. Herein, for the first time, the atomic and electronic structures of SnSe surfaces are studied by a home-built low temperature scanning tunneling microscope (STM) and density functional theory (DFT) calculations. The cleaved surface of SnSe is comprised of covalently bonded Se and Sn atoms in zigzag patterns. However, rectangular periodicity was observed in the atomic images of SnSe surfaces for filled and empty state probing. Detailed atomic structures are analyzed by DFT calculations, indicating that the bright extrusions of both filled and empty state images are mostly located at the positions of Sn atoms.

Preparing and Restoring Composite Resin Restorations. The Advantage of High Magnification Loupes or the Dental Surgical Operating Microscope.

PubMed

Mamoun, John

2015-01-01

Use of magnification, such as 6x to 8x binocular surgical loupes or the surgical operating microscope, combined with co-axial illumination, may facilitate the creation of stable composite resin restorations that are less likely to develop caries, cracks or margin stains over years of service. Microscopes facilitate observation of clinically relevant microscopic visual details, such as microscopic amounts of demineralization or caries at preparation margins; microscopic areas of soft, decayed tooth structure; microscopic amounts of moisture contamination of the preparation during bonding; or microscopic marginal gaps in the composite. Preventing microscope-level errors in composite fabrication can result in a composite restoration that, at initial placement, appears perfect when viewed under 6x to 8x magnification and which also is free of secondary caries, marginal staining or cracks at multi-year follow-up visits.

Imaging the microscopic structure of shear thinning and thickening colloidal suspensions.

PubMed

Cheng, Xiang; McCoy, Jonathan H; Israelachvili, Jacob N; Cohen, Itai

2011-09-02

The viscosity of colloidal suspensions varies with shear rate, an important effect encountered in many natural and industrial processes. Although this non-Newtonian behavior is believed to arise from the arrangement of suspended particles and their mutual interactions, microscopic particle dynamics are difficult to measure. By combining fast confocal microscopy with simultaneous force measurements, we systematically investigate a suspension's structure as it transitions through regimes of different flow signatures. Our measurements of the microscopic single-particle dynamics show that shear thinning results from the decreased relative contribution of entropic forces and that shear thickening arises from particle clustering induced by hydrodynamic lubrication forces. This combination of techniques illustrates an approach that complements current methods for determining the microscopic origins of non-Newtonian flow behavior in complex fluids.

Remodeling Science Education

ERIC Educational Resources Information Center

Hestenes, David

2013-01-01

Radical reform in science and mathematics education is needed to prepare citizens for challenges of the emerging knowledge-based global economy. We consider definite proposals to establish: (1) "Standards of science and math literacy" for all students. (2) "Integration of the science curriculum" with structure of matter,…

Secondary electron imaging of monolayer materials inside a transmission electron microscope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cretu, Ovidiu, E-mail: cretu.ovidiu@nims.go.jp; Lin, Yung-Chang; Suenaga, Kazutomo

2015-08-10

A scanning transmission electron microscope equipped with a backscattered and secondary electron detector is shown capable to image graphene and hexagonal boron nitride monolayers. Secondary electron contrasts of the two lightest monolayer materials are clearly distinguished from the vacuum level. A signal difference between these two materials is attributed to electronic structure differences, which will influence the escape probabilities of the secondary electrons. Our results show that the secondary electron signal can be used to distinguish between the electronic structures of materials with atomic layer sensitivity, enhancing its applicability as a complementary signal in the analytical microscope.

Pulsatile Fluid Shear in Bone Remodeling

NASA Technical Reports Server (NTRS)

Frangos, John A.

1997-01-01

The objective of this investigation was to elucidate the sensitivity to transients in fluid shear stress in bone remodeling. Bone remodeling is clearly a function of the local mechanical environment which includes interstitial fluid flow. Traditionally, load-induced remodeling has been associated with low frequency (1-2 Hz) signals attributed to normal locomotion. McLeod and Rubin, however, demonstrated in vivo remodeling events associated with high frequency (15-30 Hz) loading. Likewise, other in vivo studies demonstrated that slowly applied strains did not trigger remodeling events. We therefore hypothesized that the mechanosensitive pathways which control bone maintenance and remodeling are differentially sensitive to varying rates of applied fluid shear stress.

Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise.

PubMed

Sanz-de la Garza, Maria; Rubies, Cira; Batlle, Montserrat; Bijnens, Bart H; Mont, Lluis; Sitges, Marta; Guasch, Eduard

2017-09-01

Arrhythmogenic right ventricular (RV) remodeling has been reported in response to regular training, but it remains unclear how exercise intensity affects the presence and extent of such remodeling. We aimed to assess the relationship between RV remodeling and exercise load in a long-term endurance training model. Wistar rats were conditioned to run at moderate (MOD; 45 min, 30 cm/s) or intense (INT; 60 min, 60 cm/s) workloads for 16 wk; sedentary rats served as controls. Cardiac remodeling was assessed with standard echocardiographic and tissue Doppler techniques, sensor-tip pressure catheters, and pressure-volume loop analyses. After MOD training, both ventricles similarly dilated (~16%); the RV apical segment deformation, but not the basal segment deformation, was increased [apical strain rate (SR): -2.9 ± 0.5 vs. -3.3 ± 0.6 s -1 , SED vs. MOD]. INT training prompted marked RV dilatation (~26%) but did not further dilate the left ventricle (LV). A reduction in both RV segments' deformation in INT rats (apical SR: -3.3 ± 0.6 vs. -3.0 ± 0.4 s -1 and basal SR: -3.3 ± 0.7 vs. -2.7 ± 0.6 s -1 , MOD vs. INT) led to decreased global contractile function (maximal rate of rise of LV pressure: 2.53 ± 0.15 vs. 2.17 ± 0.116 mmHg/ms, MOD vs. INT). Echocardiography and hemodynamics consistently pointed to impaired RV diastolic function in INT rats. LV systolic and diastolic functions remained unchanged in all groups. In conclusion, we showed a biphasic, unbalanced RV remodeling response with increasing doses of exercise: physiological adaptation after MOD training turns adverse with INT training, involving disproportionate RV dilatation, decreased contractility, and impaired diastolic function. Our findings support the existence of an exercise load threshold beyond which cardiac remodeling becomes maladaptive. NEW & NOTEWORTHY Exercise promotes left ventricular eccentric hypertrophy with no changes in systolic or diastolic function in healthy rats. Conversely, right ventricular adaptation to physical activity follows a biphasic, dose-dependent, and segmentary pattern. Moderate exercise promotes a mild systolic function enhancement at the right ventricular apex and more intense exercise impairs systolic and diastolic function. Copyright © 2017 the American Physiological Society.

Long-term cardiovascular changes following creation of arteriovenous fistula in patients with end stage renal disease.

PubMed

Reddy, Yogesh N V; Obokata, Masaru; Dean, Patrick G; Melenovsky, Vojtech; Nath, Karl A; Borlaug, Barry A

2017-06-21

Short-term studies have reported left ventricular (LV) dilatation following surgical creation of arteriovenous fistulas (AVF) or arteriovenous grafts (AVGs), but chronic cardiac structural and functional changes have not been examined or related to clinical outcomes following AVF/AVG. We sought to characterize the long-term changes in cardiac structure and function in patients undergoing shunt creation for haemodialysis. A retrospective analysis was performed of patients undergoing echocardiography before and after surgical AVF/AVG creation for the initiation of haemodialysis. 137 patients underwent echocardiographic examinations prior to AVF and 2.6 years (median) after AVF creation. Following AVF and dialysis initiation, there were reductions in blood pressure, body weight and estimated plasma volume coupled with modest reverse LV remodelling. In contrast, AVF/AVG creation was associated with significant right ventricular (RV) dilatation and deterioration in RV function. Incident heart failure (HF) developed in 43% of patients in tandem with greater RV remodeling. The development of RV dilation following surgical AVF/AVG was independently associated with increased risk of death [HR 3.9, 95% CI (1.7-9.2), P = 0.001]. In long-term follow-up, RV remodelling and dysfunction develop following AVF/AVG creation and dialysis initiation, despite improved control of LV pressure load through dialysis. Deleterious effects on right heart structure and function are coupled with development of incident HF and increased risk of death. Further study is required to identify patients at greatest risk for detrimental AVF/AVG changes who may benefit from alternate forms of dialysis or potentially ligation of existing AVF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Chronic hemodynamic overload of the atria is an important factor for gap junction remodeling in human and rat hearts.

PubMed

Rucker-Martin, Catherine; Milliez, Paul; Tan, Sisareuth; Decrouy, Xavier; Recouvreur, Michel; Vranckx, Roger; Delcayre, Claude; Renaud, Jean-François; Dunia, Irene; Segretain, Dominique; Hatem, Stéphane N

2006-10-01

The expression and distribution of connexins is abnormal in a number of cardiac diseases, including atrial fibrillation, and is believed to favor conduction slowing and arrhythmia. Here, we studied the role of atrial structural remodeling in the disorganization of gap junctions and whether redistributed connexins can form new functional junction channels. Expression of connexin-43 (Cx43) was characterized by immunoblotting and immunohistochemistry in human right atrial specimens and in rat atria after myocardial infarction (MI). Gap junctions were studied by electron and 3-D microscopy, and myocyte-myocyte coupling was determined by Lucifer yellow dye transfer. In both chronically hemodynamically overloaded human atria in sinus rhythm and in dilated atria from MI-rats, Cx43 were dephosphorylated and redistributed from the intercalated disc to the lateral cell membranes as observed during atrial fibrillation. In MI-rats, the gap junctions at the intercalated disc were smaller (20% decrease) and contained very little Cx43 (0 or 1 gold particle vs. 42 to 98 in sham-operated rats). In the lateral membranes of myocytes, numerous connexon aggregates comprising non-phosphorylated Cx43 were observed. These connexon aggregates were in no case assembled into gap junction plaque-like structures. However, N-cadherin was well organized in the intercalated disc. There was very little myocyte-myocyte coupling in MI-rat atria and no myocyte-fibroblast coupling. Regression of the atrial remodeling was associated with the normalization of Cx43 localization. Structural alteration of the atrial myocardium is an important factor in the disorganization of connexins and gap junction. Moreover, redistributed Cx43 do not form junction channels.

Excessive interatrial adiposity is associated with left atrial remodeling, augmented contractile performance in asymptomatic population.

PubMed

Lai, Yau-Huei; Yun, Chun-Ho; Su, Cheng-Huang; Yang, Fei-Shih; Yeh, Hung-I; Hou, Charles Jia-Yin; Wu, Tung-Hsin; Cury, Ricardo C; Bezerra, Hiram G; Hung, Chung-Lieh

2016-03-01

Pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. Data regarding the mechanistic link between such measures and left atrial (LA) structural/functional remodeling, a clinical hallmark of early stage heart failure (HF) and atrial fibrillation (AF) incidence, in asymptomatic population remain largely unexplored. This retrospective analysis includes 356 subjects free from significant valvular disorders, atrial fibrillation, or clinical HF. Regional adipose tissue including pericardial and periaortic fat volumes, interatrial septal (IAS), and left atrioventricular groove (AVG) fat thickness were all measured by multidetector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We measured LA volumes, booster performance, reservoir capacity as well as conduit function, and analyzed their association with adiposity measures. All four adiposity measures were positively associated with greater LA volumes (all P < 0.05), while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P < 0.01). In multivariate models, IAS fat thickness remained independently associated with larger LA volumes, increased LA kinetic energy and ejection force (β-coef: 0.17 & 0.15, both P < 0.05), and impaired LA reservoir and conduit function (β-coef: -0.20 & -0.12, both P < 0.05) after adjusting for clinical variables. Accumulated visceral adiposity, especially interatrial fat depots, was associated with certain LA structural/functional remodeling characterized by impaired LA reservoir and conduit function though augmented kinetic energy and ejection performance. Our data suggested that interatrial fat burden may be associated with certain detrimental LA functions with compensatory LA adaptation in an asymptomatic population. © 2016 The authors.

Cardio-protection of ultrafine granular powder for Salvia miltiorrhiza Bunge against myocardial infarction.

PubMed

Wang, Linlin; Li, Yuanmin; Deng, Wen; Dong, Zhihui; Li, Xue; Liu, Dan; Zhao, Lijie; Fu, Weiguo; Cho, Kenka; Niu, Huaying; Guo, Dean; Cheng, Jinle; Jiang, Baohong

2018-08-10

Myocardial infarction (MI) is considered as the major inducer to the morbidity and mortality related to coronary occlusion. Salvia miltiorrhiza Bunge is widely applied in the clinic for the prevention and treatment of heart diseases. The preparation of traditional herb decoction (THD) is not only time consuming but also difficult to keep uniform for every time. New usage form of Salvia miltiorrhiza Bunge with characteristics of convenience, uniform and efficiency is needed. The aims of present study were to investigate the cardio-protection of ultrafine granular powder (UGP) of Salvia miltiorrhiza Bunge; and further compare the characteristics of UGP with THD. MI was induced by ligation of the left anterior descending coronary artery near the main pulmonary artery. Cardio-protection of UGP or THD was evaluated based on two sets of experiments, one was acute myocardial infarction (AMI) through 7 days preventive administration, and the other one was chronic cardiac remodeling through 28 days therapeutic administration. Hemodynamic measurement was conducted to evaluate heart function and histopathological detection was used to evaluate heart structure. No significant improvement of heart structure and function was detected for preventive administration of UGP or THD on AMI rats. While, more significant improvements on left ventricular systolic and diastolic function were detected with therapeutic treatment with 0.81 g/kg UGP than same dose of THD on rats against chronic cardiac remodeling. Both UGP and THD showed the protective effects on heart structure, especially against fibrosis with long-term therapeutic treatment. As a new usage form of Salvia miltiorrhiza Bunge, UGP showed significant cardio-protection against myocardial remodeling with therapeutic treatment. Comparing with THD, UGP also holds the advantages of uniform, convenience and efficiency. Copyright © 2018 Elsevier B.V. All rights reserved.

New Concepts in the Invasive and Non Invasive Evaluation of Remodelling of the Right Ventricle and Pulmonary Vasculature in Pulmonary Arterial Hypertension

PubMed Central

Domingo, Enric; Aguilar, Rio; López-Meseguer, Manuel; Teixidó, Gisela; Vazquez, Manuel; Roman, Antonio

2009-01-01

Pulmonary arterial hypertension (PAH) is a rare fatal disease defined as a sustained elevation of pulmonary arterial pressure to more than 25 mmHg at rest, with a mean pulmonary-capillary wedge pressure and left ventricular enddiastolic pressure of less than 15 mmHg at rest. Histopathology of PAH is founded on structural modifications on the vascular wall of small pulmonary arteries characterized by thickening of all its layers. These changes, named as vascular remodelling, include vascular proliferation, fibrosis, and vessel obstruction. In clinical practice the diagnosis of PAH relies on measurements of pulmonary vascular pressure and cardiac output, and calculation of pulmonary vascular resistances. Direct evaluation of pulmonary vascular structure is not routinely performed in pulmonary hypertension since current imaging techniques are limited and since little is known about the relationship between structural changes and functional characteristics of the pulmonary vasculature. Intravascular ultrasound studies in patients with pulmonary hypertension have shown a thicker middle layer, increased wall-thickness ratio and diminished pulsatility than in control patients. Optical Coherence Tomography, a new high resolution imaging modality that has proven its superiority over intravascular ultrasound (IVUS) for the detection and characterization of coronary atherosclerotic plaque composition, may potentially be a useful technique for the in vivo study of the pulmonary arterial wall. In addition current progress in Echo Doppler technique will quantify right ventricular function with parameters independent of loading conditions and not requiring volumetric approximations of the complex geometry of the right ventricle. This would allow the in vivo study of right ventricular and pulmonary artery remodelling in PAH. PMID:19452037

MicroRNAs in right ventricular remodelling.

PubMed

Batkai, Sandor; Bär, Christian; Thum, Thomas

2017-10-01

Right ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology selectively affects the RV, leading to a distinct RV-specific clinical phenotype. MicroRNAs have been identified as key regulators of biological processes that drive the progression of chronic diseases. The role of microRNAs in diseases affecting the left ventricle has been studied for many years, however there is still limited information on microRNAs specific to diseases in the right ventricle. Here, we review recently described details on the expression, regulation, and function of microRNAs in the pathological remodelling of the right heart. Recently identified strategies using microRNAs as pharmacological targets or biomarkers will be highlighted. Increasing knowledge of pathogenic microRNAs will finally help improve our understanding of underlying distinct mechanisms and help utilize novel targets or biomarkers to develop treatments for patients suffering from right heart diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Biomechanics of Cardiac Function

PubMed Central

Voorhees, Andrew P.; Han, Hai-Chao

2015-01-01

The heart pumps blood to maintain circulation and ensure the delivery of oxygenated blood to all the organs of the body. Mechanics play a critical role in governing and regulating heart function under both normal and pathological conditions. Biological processes and mechanical stress are coupled together in regulating myocyte function and extracellular matrix structure thus controlling heart function. Here we offer a brief introduction to the biomechanics of left ventricular function and then summarize recent progress in the study of the effects of mechanical stress on ventricular wall remodeling and cardiac function as well as the effects of wall mechanical properties on cardiac function in normal and dysfunctional hearts. Various mechanical models to determine wall stress and cardiac function in normal and diseased hearts with both systolic and diastolic dysfunction are discussed. The results of these studies have enhanced our understanding of the biomechanical mechanism in the development and remodeling of normal and dysfunctional hearts. Biomechanics provide a tool to understand the mechanism of left ventricular remodeling in diastolic and systolic dysfunction and guidance in designing and developing new treatments. PMID:26426462

In vivo imaging of basement membrane movement: ECM patterning shapes Hydra polyps.

PubMed

Aufschnaiter, Roland; Zamir, Evan A; Little, Charles D; Özbek, Suat; Münder, Sandra; David, Charles N; Li, Li; Sarras, Michael P; Zhang, Xiaoming

2011-12-01

Growth and morphogenesis during embryonic development, asexual reproduction and regeneration require extensive remodeling of the extracellular matrix (ECM). We used the simple metazoan Hydra to examine the fate of ECM during tissue morphogenesis and asexual budding. In growing Hydra, epithelial cells constantly move towards the extremities of the animal and into outgrowing buds. It is not known, whether these tissue movements involve epithelial migration relative to the underlying matrix or whether cells and ECM are displaced as a composite structure. Furthermore, it is unclear, how the ECM is remodeled to adapt to the shape of developing buds and tentacles. To address these questions, we used a new in vivo labeling technique for Hydra collagen-1 and laminin, and tracked the fate of ECM in all body regions of the animal. Our results reveal that Hydra 'tissue movements' are largely displacements of epithelial cells together with associated ECM. By contrast, during the evagination of buds and tentacles, extensive movement of epithelial cells relative to the matrix is observed, together with local ECM remodeling. These findings provide new insights into the nature of growth and morphogenesis in epithelial tissues.

Structure and membrane remodeling activity of ESCRT-III helical polymers

DOE PAGES

McCullough, John; Clippinger, Amy K.; Talledge, Nathaniel; ...

2015-12-18

The endosomal sorting complexes required for transport (ESCRT) proteins mediate fundamental membrane remodeling events that require stabilizing negative membrane curvature. These include endosomal intralumenal vesicle formation, HIV budding, nuclear envelope closure, and cytokinetic abscission. ESCRT-III subunits perform key roles in these processes by changing conformation and polymerizing into membrane-remodeling filaments. Here, we report the 4 angstrom resolution cryogenic electron microscopy reconstruction of a one-start, double-stranded helical copolymer composed of two different human ESCRT-III subunits, charged multivesicular body protein 1B (CHMP1B) and increased sodium tolerance 1 (IST1). The inner strand comprises “open” CHMP1B subunits that interlock in an elaborate domain-swapped architecturemore » and is encircled by an outer strand of “closed” IST1 subunits. Unlike other ESCRT-III proteins, CHMP1B and IST1 polymers form external coats on positively curved membranes in vitro and in vivo. In conclusion, our analysis suggests how common ESCRT-III filament architectures could stabilize different degrees and directions of membrane curvature.« less

Ex vivo study of the home-use TriPollar RF device using an experimental human skin model.

PubMed

Boisnic, Sylvie; Branchet, Marie Christine

2010-09-01

A wide variety of professional radio frequency (RF) aesthetic treatments for anti-aging are available aiming at skin tightening. A new home-use RF device for facial treatments has recently been developed based on TriPollar technology. To evaluate the mechanism of the new home-use device, in the process of collagen remodeling, using an ex vivo skin model. Human skin samples were collected in order to evaluate the anti-aging effect of a home-use device for facial treatments on an ex vivo human skin model. Skin tightening was evaluated by dermal histology, quantitative analysis of collagen fibers and dosage of collagen synthesis. Significant collagen remodeling following RF treatment with the device was found in the superficial and mid-deep dermis. Biochemical measurement of newly synthesized collagen showed an increase of 41% in the treated samples as compared to UV-aged control samples. The new home-use device has been demonstrated to affect significant collagen remodeling, in terms of the structural and biochemical improvement of dermal collagen on treated skin samples.

LIPS database with LIPService: a microscopic image database of intracellular structures in Arabidopsis guard cells.

PubMed

Higaki, Takumi; Kutsuna, Natsumaro; Hasezawa, Seiichiro

2013-05-16

Intracellular configuration is an important feature of cell status. Recent advances in microscopic imaging techniques allow us to easily obtain a large number of microscopic images of intracellular structures. In this circumstance, automated microscopic image recognition techniques are of extreme importance to future phenomics/visible screening approaches. However, there was no benchmark microscopic image dataset for intracellular organelles in a specified plant cell type. We previously established the Live Images of Plant Stomata (LIPS) database, a publicly available collection of optical-section images of various intracellular structures of plant guard cells, as a model system of environmental signal perception and transduction. Here we report recent updates to the LIPS database and the establishment of a database table, LIPService. We updated the LIPS dataset and established a new interface named LIPService to promote efficient inspection of intracellular structure configurations. Cell nuclei, microtubules, actin microfilaments, mitochondria, chloroplasts, endoplasmic reticulum, peroxisomes, endosomes, Golgi bodies, and vacuoles can be filtered using probe names or morphometric parameters such as stomatal aperture. In addition to the serial optical sectional images of the original LIPS database, new volume-rendering data for easy web browsing of three-dimensional intracellular structures have been released to allow easy inspection of their configurations or relationships with cell status/morphology. We also demonstrated the utility of the new LIPS image database for automated organelle recognition of images from another plant cell image database with image clustering analyses. The updated LIPS database provides a benchmark image dataset for representative intracellular structures in Arabidopsis guard cells. The newly released LIPService allows users to inspect the relationship between organellar three-dimensional configurations and morphometrical parameters.

Phase-shifting interference microscope with extendable field of measurement

NASA Astrophysics Data System (ADS)

Lin, Shyh-Tsong; Hsu, Wei-Feng; Wang, Ming-Shiang

2018-04-01

An innovative phase-shifting interference microscope aimed at extending the field of measurement is proposed in this paper. The microscope comprises a light source module, a phase modulation module, and an interferometric module, which reconstructs the micro-structure contours of samples using the five-step phase-shifting algorithm. This paper discusses the measurement theory and outlines the configuration, experimental setup, and experimental results obtained using the proposed interference microscope. The results confirm the efficacy of the microscope, achieving a standard deviation of 2.4 nm from a step height of 86.2 nm in multiple examinations.

Refined tip preparation by electrochemical etching and ultrahigh vacuum treatment to obtain atomically sharp tips for scanning tunneling microscope and atomic force microscope.

PubMed

Hagedorn, Till; El Ouali, Mehdi; Paul, William; Oliver, David; Miyahara, Yoichi; Grütter, Peter

2011-11-01

A modification of the common electrochemical etching setup is presented. The described method reproducibly yields sharp tungsten tips for usage in the scanning tunneling microscope and tuning fork atomic force microscope. In situ treatment under ultrahigh vacuum (p ≤10(-10) mbar) conditions for cleaning and fine sharpening with minimal blunting is described. The structure of the microscopic apex of these tips is atomically resolved with field ion microscopy and cross checked with field emission. © 2011 American Institute of Physics

Developing an Energy Performance Modeling Startup Kit

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

2012-10-01

In 2011, the NAHB Research Center began assessing the needs and motivations of residential remodelers regarding energy performance remodeling. This report outlines: the current remodeling industry and the role of energy efficiency; gaps and barriers to adding energy efficiency into remodeling; and support needs of professional remodelers to increase sales and projects involving improving home energy efficiency.

Regulation of adult cardiocyte growth: effects of active and passive mechanical loading

NASA Technical Reports Server (NTRS)

Decker, M. L.; Janes, D. M.; Barclay, M. M.; Harger, L.; Decker, R. S.

1997-01-01

Fluctuations in hemodynamic load have been documented to modulate contractile protein turnover and myofibrillar structure in the heart; however, the relative importance of active and passive loading in regulating adult cardiocyte growth remains unresolved. To address this issue at the cellular level, adult feline cardiocytes were cultured either on Silastic membranes or plastic surfaces. Cardiocyte-laden membranes were stretched 10% of their rest length to enhance passive loading, whereas heart cells cultured on plastic or Silastic were field stimulated at 1 Hz to mimic active loading. Turnover of contractile proteins and structural integrity of the contractile-cytoskeletal apparatus were monitored for periods ranging from 4 to 72 h. Active and passive loading elevated contractile protein synthesis nearly equally (approximately 50%) and promoted the attachment of remodeled myofibrils to vinculin-positive focal contacts and/or costameres during the first 24 h of loading. Thereafter, rates of contractile protein synthesis returned to control values in passively stretched heart cells but remained elevated in field-stimulated cultures. The fractional rate of growth was increased significantly (approximately 8%/day) in electrically paced cells, whereas in passively stretched cardiocytes the growth rate rose only modestly (approximately 2%/day). Changes in the rate of myocyte growth appeared more closely correlated with the development of focal contacts and myofibril remodeling than with changes in myofibrillar protein turnover per se. 2,3-Butanedione monoxime, nifedipine, and, to a lesser extent, ryanodine blocked field-stimulated contractile protein synthesis and myofibrillar remodeling but had no impact on protein turnover or myofibril reassembly in passively loaded cardiocytes. The results of these experiments imply that both active and passive loading stimulate contractile protein turnover and myofibril remodeling, but the generation of active tension accelerates cardiocyte growth to a greater extent than passive loading. Furthermore, pharmacological interventions suggest that unique pathways may mediate these cellular events in actively and passively loaded adult cardiocytes.

Regulation of adult cardiocyte growth: effects of active and passive mechanical loading.

PubMed

Decker, M L; Janes, D M; Barclay, M M; Harger, L; Decker, R S

1997-06-01

Fluctuations in hemodynamic load have been documented to modulate contractile protein turnover and myofibrillar structure in the heart; however, the relative importance of active and passive loading in regulating adult cardiocyte growth remains unresolved. To address this issue at the cellular level, adult feline cardiocytes were cultured either on Silastic membranes or plastic surfaces. Cardiocyte-laden membranes were stretched 10% of their rest length to enhance passive loading, whereas heart cells cultured on plastic or Silastic were field stimulated at 1 Hz to mimic active loading. Turnover of contractile proteins and structural integrity of the contractile-cytoskeletal apparatus were monitored for periods ranging from 4 to 72 h. Active and passive loading elevated contractile protein synthesis nearly equally (approximately 50%) and promoted the attachment of remodeled myofibrils to vinculin-positive focal contacts and/or costameres during the first 24 h of loading. Thereafter, rates of contractile protein synthesis returned to control values in passively stretched heart cells but remained elevated in field-stimulated cultures. The fractional rate of growth was increased significantly (approximately 8%/day) in electrically paced cells, whereas in passively stretched cardiocytes the growth rate rose only modestly (approximately 2%/day). Changes in the rate of myocyte growth appeared more closely correlated with the development of focal contacts and myofibril remodeling than with changes in myofibrillar protein turnover per se. 2,3-Butanedione monoxime, nifedipine, and, to a lesser extent, ryanodine blocked field-stimulated contractile protein synthesis and myofibrillar remodeling but had no impact on protein turnover or myofibril reassembly in passively loaded cardiocytes. The results of these experiments imply that both active and passive loading stimulate contractile protein turnover and myofibril remodeling, but the generation of active tension accelerates cardiocyte growth to a greater extent than passive loading. Furthermore, pharmacological interventions suggest that unique pathways may mediate these cellular events in actively and passively loaded adult cardiocytes.

Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

PubMed Central

Astorga, Cristian R.; González-Candia, Alejandro; Candia, Alejandro A.; Figueroa, Esteban G.; Cañas, Daniel; Ebensperger, Germán; Reyes, Roberto V.; Llanos, Aníbal J.; Herrera, Emilio A.

2018-01-01

Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs (Ovis aries) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05). This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05) and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia. PMID:29559926

Minimizing Surface Exposure to Climate Extremity in Coastal Megacities by Structure Remodelling using Integral Geographic Information System: Lessons from Greater Mumbai Metropolitan

NASA Astrophysics Data System (ADS)

Tiwari, A.

2016-12-01

Coastal metropolitans in South Asia represent the most densely populated and congested urban spaces ranking among the largest urban settlements of the planet. These megacities are characterized by inadequate infrastructure, lack of mitigation tools, and weak resilience of urban ecosystems. Additionally, climate change has increased vulnerability of poor and marginalized population living in rapidly growing coastal megacities to increased frequency, severity and intensity of extreme weather events. This has adversely affected local counter strategies and adaptation tools, transforming such events into hazards with the inability to respond and mitigate. Study aimed to develop a participatory framework for risk reduction in Greater Mumbai Metropolitan by Structure Remodeling (SR) in integral GIS. Research utilized terrain analysis tools and vulnerability mapping, and identified risk susceptible fabric and checked its scope for SR without: 1.adding to its (often) complex fragmentation, and 2.without interference with the ecosystem services accommodated by it. Surfaces available included paved ground, streetscapes commercial facades, rooftops,public spaces, open as well as dark spaces. Remodeling altered certain characteristics in the intrinsic or extrinsic cross-section profile or in both (if suitable) with infrastructure measures (grey, green, blue) that collectively involved ecosystem services and maintained natural hydrological connection. This method fairly reduced exposure of vulnerable surface and minimized risk to achieve extremity-neutral state. Harmonizing with public perception and incorporating priorities of local authorities, the method is significant as it rises above the fundamental challenges arising during management of (often) conflicting perspectives and interests of multiplicity of stakeholders involved at various levels in urban climate governance while ensuring inclusive solutions with reduced vulnerability and increased resilience. Additionally this method has vast potential to replicate for climate smart planning beyond the study region as it clearly ensures barrier free climate-communication process for decision making while looking for long term feasible outcomes of remodeled surface through the most affordable and innovative tools.

New mechanisms and targets in the treatment of bone fragility.

PubMed

Martin, T John; Seeman, Ego

2007-01-01

Bone modelling and remodelling are cell-mediated processes responsible for the construction and reconstruction of the skeleton throughout life. These processes are chiefly mediated by locally generated cytokines and growth factors that regulate the differentiation, activation, work and life span of osteoblasts and osteoclasts, the cells that co-ordinate the volumes of bone resorbed and formed. In this way, the material composition and structural design of bone is regulated in accordance with its loading requirements. Abnormalities in this regulatory system compromise the material and structural determinants of bone strength producing bone fragility. Understanding the intercellular control processes that regulate bone modelling and remodelling is essential in planning therapeutic approaches to prevention and treatment of bone fragility. A great deal has been learnt in the last decade. Clinical trials carried out exclusively with drugs that inhibit bone resorption have identified the importance of reducing the rate of bone remodelling and so the progression of bone fragility to achieved fracture reductions of approx. 50%. These trials have also identified limitations that should be placed upon interpretation of bone mineral density changes in relation to treatment. New resorption inhibitors are being developed, based on mechanisms of action that are different from existing drugs. Some of these might offer resorption inhibition without reducing bone formation. More recent research has provided the first effective anabolic therapy for bone reconstruction. Daily injections of PTH (parathyroid hormone)-(1-34) have been shown in preclinical studies and in a large clinical trial to increase bone tissue mass and reduce the risk of fractures. The action of PTH differs from that of the resorption inhibitors, but whether it is more effective in fracture reduction is not known. Understanding the cellular and molecular mechanisms of PTH action, particularly its interactions with other pathways in determining bone formation, is likely to lead to new therapeutic developments. The recent discovery through mouse genetics that PTHrP (PTH-related protein) is a crucial bone-derived paracrine regulator of remodelling offers new and interesting therapeutic targets.

Understanding External Cervical Resorption in Vital Teeth.

PubMed

Mavridou, Athina M; Hauben, Esther; Wevers, Martine; Schepers, Evert; Bergmans, Lars; Lambrechts, Paul

2016-12-01

The aim of this study was to investigate the 3-dimensional (3D) structure and the cellular and tissue characteristics of external cervical resorption (ECR) in vital teeth and to understand the phenomenon of ECR by combining histomorphological and radiographic findings. Twenty-seven cases of vital permanent teeth displaying ECR were investigated. ECR diagnosis was based on clinical and radiographic examination with cone-beam computed tomographic imaging. The extracted teeth were further analyzed by using nanofocus computed tomographic imaging, hard tissue histology, and scanning electron microscopy. All examined teeth showed some common characteristics. Based on the clinical and experimental findings, a 3-stage mechanism of ECR was proposed. At the first stage (ie, the initiation stage), ECR was initiated at the cementum below the gingival epithelial attachment. At the second stage (ie, the resorption stage), the resorption invaded the tooth structure 3-dimensionally toward the pulp space. However, it did not penetrate the pulp space because of the presence of a pericanalar resorption-resistant sheet. This layer was observed to consist of predentin, dentin, and occasionally reparative mineralized (bonelike) tissue, having a fluctuating thickness averaging 210 μm. At the last advanced stage (ie, the repair stage), repair took place by an ingrowth and apposition of bonelike tissue into the resorption cavity. During the reparative stage, repair and remodeling phenomena evolve simultaneously, whereas both resorption and reparative stages progress in parallel at different areas of the tooth. ECR is a dynamic and complex condition that involves periodontal and endodontic tissues. Using clinical, histologic, radiographic, and scanning microscopic analysis, a better understanding of the evolution of ECR is possible. Based on the experimental findings, a 3-stage mechanism for the initiation and growth of ECR is proposed. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The Potential Protective Effects of 2-aminoethyl Diphenylborinate against Inner Ear Acoustic Trauma: Experimental Study Using Transmission and Scanning Electron Microscopy.

PubMed

Kaymakçı, Mustafa; Acar, Mustafa; Burukoglu, Dilek; Kutlu, Hatice Mehtap; Shojaolsadati, Paria; Cingi, Cemal; Bayar Muluk, Nuray

2015-04-01

In this prospective experimental study, we investigated the preventive effects of 2-aminoethyl diphenylborinate (2-APB) in rats exposed to acoustic trauma (AT). Light microscopic, transmission electron microscopic (TEM), and scanning electron microscopic (SEM) examinations were performed. Eighteen healthy Wistar albino rats were divided into the following three groups: groups 1 (control), 2 (AT), and 3 (AT+APB). The rats in groups 2 and 3 were exposed to AT; in group 3 rats, 2-APB at 2 mg/kg was also administered, initially transperitoneally, after 10 min. During the light microscopic, TEM, and SEM examinations, the structures of the cochlear hair cells, stereocilia, and Deiter's cells were normal in the control group. In the AT group, the organ of Corti and proximate structures were damaged according to the light microscopic examination. During the TEM examination, intense cellular damage and stereocilia loss were detected, while during the SEM examination, extensive damage and stereocilia loss were observed. Decreased damage with preserved cochlear structure was detected during the light microscopic examination in the AT+APB group than in the AT group. During the TEM and SEM examinations, although stereocilia loss occurred in the AT+APB group, near-normal cell, cilia, and tectorial membrane structures were also observed in the AT+APB group compared with the AT group. 2-APB may have protective effects against AT damage of the cochlea. The main mechanism underlying this effect is the inhibition of the vasoconstriction of the cochlear spiral modiolar artery, thereby improving cochlear blood flow. We conclude that 2-APB may also be effective if used immediately following AT.

The evolution of structured illumination microscopy in studies of HIV.

PubMed

Marno, Kelly; Al'Zoubi, Lara; Pearson, Matthew; Posch, Markus; McKnight, Áine; Wheeler, Ann P

2015-10-15

The resolution limit of conventional light microscopy has proven to be limiting for many biological structures such as viruses including Human immunodeficiency virus (HIV). Individual HIV virions are impossible to study using confocal microscopy as they are well below the 200 nm resolution limit of conventional light microscopes. Structured illumination microscopy (SIM) allows a twofold enhancement in image resolution compared to standard widefield illumination and so provides an excellent tool for study of HIV. Viral capsids (CAs) vary between 110 and 146 nm so this study challenges the performance of SIM microscopes. SIM microscopy was first developed in 2000, commercialised in 2007 and rapidly developed. Here we present the changes in capabilities of the SIM microscopes for study of HIV localisation as the instrumentation for structured illumination microscopy has evolved over the past 8 years. Copyright © 2015. Published by Elsevier Inc.

Characterization of a subwavelength-scale 3D void structure using the FDTD-based confocal laser scanning microscopic image mapping technique.

PubMed

Choi, Kyongsik; Chon, James W; Gu, Min; Lee, Byoungho

2007-08-20

In this paper, a simple confocal laser scanning microscopic (CLSM) image mapping technique based on the finite-difference time domain (FDTD) calculation has been proposed and evaluated for characterization of a subwavelength-scale three-dimensional (3D) void structure fabricated inside polymer matrix. The FDTD simulation method adopts a focused Gaussian beam incident wave, Berenger's perfectly matched layer absorbing boundary condition, and the angular spectrum analysis method. Through the well matched simulation and experimental results of the xz-scanned 3D void structure, we first characterize the exact position and the topological shape factor of the subwavelength-scale void structure, which was fabricated by a tightly focused ultrashort pulse laser. The proposed CLSM image mapping technique based on the FDTD can be widely applied from the 3D near-field microscopic imaging, optical trapping, and evanescent wave phenomenon to the state-of-the-art bio- and nanophotonics.

A variable-temperature nanostencil compatible with a low-temperature scanning tunneling microscope/atomic force microscope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steurer, Wolfram, E-mail: wst@zurich.ibm.com; Gross, Leo; Schlittler, Reto R.

2014-02-15

We describe a nanostencil lithography tool capable of operating at variable temperatures down to 30 K. The setup is compatible with a combined low-temperature scanning tunneling microscope/atomic force microscope located within the same ultra-high-vacuum apparatus. The lateral movement capability of the mask allows the patterning of complex structures. To demonstrate operational functionality of the tool and estimate temperature drift and blurring, we fabricated LiF and NaCl nanostructures on Cu(111) at 77 K.

A variable-temperature nanostencil compatible with a low-temperature scanning tunneling microscope/atomic force microscope.

PubMed

Steurer, Wolfram; Gross, Leo; Schlittler, Reto R; Meyer, Gerhard

2014-02-01

We describe a nanostencil lithography tool capable of operating at variable temperatures down to 30 K. The setup is compatible with a combined low-temperature scanning tunneling microscope/atomic force microscope located within the same ultra-high-vacuum apparatus. The lateral movement capability of the mask allows the patterning of complex structures. To demonstrate operational functionality of the tool and estimate temperature drift and blurring, we fabricated LiF and NaCl nanostructures on Cu(111) at 77 K.

On microscopic structure of the QCD vacuum

NASA Astrophysics Data System (ADS)

Pak, D. G.; Lee, Bum-Hoon; Kim, Youngman; Tsukioka, Takuya; Zhang, P. M.

2018-05-01

We propose a new class of regular stationary axially symmetric solutions in a pure QCD which correspond to monopole-antimonopole pairs at macroscopic scale. The solutions represent vacuum field configurations which are locally stable against quantum gluon fluctuations in any small space-time vicinity. This implies that the monopole-antimonopole pair can serve as a structural element in microscopic description of QCD vacuum formation.

Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines.

PubMed

Padamsey, Zahid; McGuinness, Lindsay; Bardo, Scott J; Reinhart, Marcia; Tong, Rudi; Hedegaard, Anne; Hart, Michael L; Emptage, Nigel J

2017-01-04

Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca 2+ stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca 2+ release from lysosomes in the dendrites. This Ca 2+ release triggered the fusion of lysosomes with the plasma membrane, resulting in the release of Cathepsin B. Cathepsin B increased the activity of matrix metalloproteinase 9 (MMP-9), an enzyme involved in extracellular matrix (ECM) remodelling and synaptic plasticity. Inhibition of either lysosomal Ca 2+ signaling or Cathepsin B release prevented the maintenance of dendritic spine growth induced by Hebbian activity. This impairment could be rescued by exogenous application of active MMP-9. Our findings suggest that activity-dependent exocytosis of Cathepsin B from lysosomes regulates the long-term structural plasticity of dendritic spines by triggering MMP-9 activation and ECM remodelling. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Ren; Boudreau, Aaron; Bissell, Mina J

Mammary gland development, functional differentiation, and homeostasis are orchestrated and sustained by a balance of biochemical and biophysical cues from the organ's microenvironment. The three-dimensional microenvironment of the mammary gland, predominantly 'encoded' by a collaboration between the extracellular matrix (ECM), hormones, and growth factors, sends signals from ECM receptors through the cytoskeletal intracellular matrix to nuclear and chromatin structures resulting in gene expression; the ECM in turn is regulated and remodeled by signals from the nucleus. In this chapter, we discuss how coordinated ECM deposition and remodeling is necessary for mammary gland development, how the ECM provides structural and biochemicalmore » cues necessary for tissue-specific function, and the role of the cytoskeleton in mediating the extra - to intracellular dialogue occurring between the nucleus and the microenvironment. When operating normally, the cytoskeletal-mediated dynamic and reciprocal integration of tissue architecture and function directs mammary gland development, tissue polarity, and ultimately, tissue-specific gene expression. Cancer occurs when these dynamic interactions go awry for an extended time.« less

The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Terrier, Olivier; Moules, Vincent; Carron, Coralie

Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus-host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtypemore » origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.« less

Endocytosis-dependent coordination of multiple actin regulators is required for wound healing

PubMed Central

Matsubayashi, Yutaka; Coulson-Gilmer, Camilla

2015-01-01

The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form “signaling centers” along the wound edge that control actin assembly. We conclude that coordination of actin assembly, AJ remodeling, and membrane traffic is required for the construction of a motile leading edge during wound healing. PMID:26216900

[Ultrastructure of the intima of human pial arteries in arterial hypertension].

PubMed

Chertok, V M; Kotsiuba, A E; Babich, E V

2009-01-01

Ultrastructure of the intima of human pial arteries obtained from 5 male cadavers of practically healthy individuals and from 8 cadavers of the patients with the intravitally diagnosed grade I arterial hypertension (AH) was studied by scanning and transmission electron microscopy. AH was found to be associated with the remodeling of the intimal structural elements in the pial arteries. In most arteries, the changes were detected in the microrelief of the luminal surface and in the permeability of the vascular endothelial lining and of the subendothelial layer. During this remodeling, some endothelial cells were found in the state of structural and functional adaptation to the elevated arterial pressure, while the others were undergoing the dystrophic changes. The latter include the cells containing lipid inclusions, as well as the endothelial cells presumably in the state of apoptosis. The destruction of the intercellular junctions, the disturbances in the endothelium permeability contributed to the development of subendothelial layer edema, resulting in its significant thickening. This layer became looser and contained abundant collagen fibrils.

Chymase-producing cells of the innate immune system are required for decidual vascular remodeling and fetal growth

PubMed Central

Meyer, Nicole; Woidacki, Katja; Knöfler, Martin; Meinhardt, Gudrun; Nowak, Désirée; Velicky, Philipp; Pollheimer, Jürgen; Zenclussen, Ana C.

2017-01-01

Intrauterine growth restriction (IUGR) is caused by insufficient remodeling of spiral arteries (SAs). The mechanism underlying the relevance of natural killer cells (NKs) and mast cells (MCs) for SA remodeling and its effects on pregnancy outcome are not well understood. We show that NK depletion arrested SA remodeling without affecting pregnancy. MC depletion resulted in abnormally remodeled SAs and IUGR. Combined absence of NKs and MCs substantially affected SA remodeling and impaired fetal growth. We found that α-chymase mast cell protease (Mcpt) 5 mediates apoptosis of uterine smooth muscle cells, a key feature of SA remodeling. Additionally, we report a previously unknown source for Mcpt5: uterine (u) NKs. Mice with selective deletion of Mcpt5+ cells had un-remodeled SAs and growth-restricted progeny. The human α-chymase CMA1, phylogenetic homolog of Mcpt5, stimulated the ex vivo migration of human trophoblasts, a pre-requisite for SA remodeling. Our results show that chymases secreted by uMCs and uNKs are pivotal to the vascular changes required to support pregnancy. Understanding the mechanisms underlying pregnancy-induced vascular changes is essential for developing therapeutic options against pregnancy complications associated with poor vascular remodeling. PMID:28327604

Fabrication and design of bioactive agent coated, highly-aligned electrospun matrices for nerve tissue engineering: Preparation, characterization and application

NASA Astrophysics Data System (ADS)

Lee, Sang Jin; Heo, Min; Lee, Donghyun; Heo, Dong Nyoung; Lim, Ho-Nam; Kwon, Il Keun

2017-12-01

In this study, we designed highly-aligned thermoplastic polycarbonate urethane (PCU) fibrous scaffolds coated with bioactive compounds, such as Poly-L-Lysine (PLL) and Poly-L-Ornithine (PLO), to enhance cellular adhesion and directivity. These products were characterized by scanning electron microscope (SEM) analysis which demonstrated that highly aligned fiber strands were formed without beads when coated onto a mandrel rotating at 1800 rpm. During in vitro cell test, PLO-coated, aligned PCU scaffolds were found to have significantly higher proliferation rates than PLL coated and bare PCU scaffolds. Interestingly, dental pulp stem cells (DPSCs) were observed to stretch along the longitudinal axis parallel to the cell direction on highly aligned scaffolds. These results clearly confirm that our strategy may suggest a useful paradigm by inducing neural tissue repair as a means to remodeling and healing of tissue for restorative procedures in neural tissue engineering.

Fluoxetine induces input-specific hippocampal dendritic spine remodeling along the septotemporal axis in adulthood and middle age.

PubMed

McAvoy, Kathleen; Russo, Craig; Kim, Shannen; Rankin, Genelle; Sahay, Amar

2015-11-01

Fluoxetine, a selective serotonin-reuptake inhibitor (SSRI), is known to induce structural rearrangements and changes in synaptic transmission in hippocampal circuitry. In the adult hippocampus, structural changes include neurogenesis, dendritic, and axonal plasticity of pyramidal and dentate granule neurons, and dedifferentiation of dentate granule neurons. However, much less is known about how chronic fluoxetine affects these processes along the septotemporal axis and during the aging process. Importantly, studies documenting the effects of fluoxetine on density and distribution of spines along different dendritic segments of dentate granule neurons and CA1 pyramidal neurons along the septotemporal axis of hippocampus in adulthood and during aging are conspicuously absent. Here, we use a transgenic mouse line in which mature dentate granule neurons and CA1 pyramidal neurons are genetically labeled with green fluorescent protein (GFP) to investigate the effects of chronic fluoxetine treatment (18 mg/kg/day) on input-specific spine remodeling and mossy fiber structural plasticity in the dorsal and ventral hippocampus in adulthood and middle age. In addition, we examine levels of adult hippocampal neurogenesis, maturation state of dentate granule neurons, neuronal activity, and glutamic acid decarboxylase-67 expression in response to chronic fluoxetine in adulthood and middle age. Our studies reveal that while chronic fluoxetine fails to augment adult hippocampal neurogenesis in middle age, the middle-aged hippocampus retains high sensitivity to changes in the dentate gyrus (DG) such as dematuration, hypoactivation, and increased glutamic acid decarboxylase 67 (GAD67) expression. Interestingly, the middle-aged hippocampus shows greater sensitivity to fluoxetine-induced input-specific synaptic remodeling than the hippocampus in adulthood with the stratum-oriens of CA1 exhibiting heightened structural plasticity. The input-specific changes and circuit-level modifications in middle-age were associated with modest enhancement in contextual fear memory precision, anxiety-like behavior and antidepressant-like behavioral responses. © 2015 Wiley Periodicals, Inc.

Fluoxetine induces input-specific hippocampal dendritic spine remodeling along the septo-temporal axis in adulthood and middle age

PubMed Central

McAvoy, Kathleen; Russo, Craig; Kim, Shannen; Rankin, Genelle; Sahay, Amar

2015-01-01

Fluoxetine, a selective serotonin-reuptake inhibitor (SSRI), is known to induce structural rearrangements and changes in synaptic transmission in hippocampal circuitry. In the adult hippocampus, structural changes include neurogenesis, dendritic and axonal plasticity of pyramidal and dentate granule neurons, and dedifferentiation of dentate granule neurons. However, much less is known about how chronic fluoxetine affects these processes along the septo-temporal axis and during the aging process. Importantly, studies documenting the effects of fluoxetine on density and distribution of spines along different dendritic segments of dentate granule neurons and CA1 pyramidal neurons along the septo-temporal axis of hippocampus in adulthood and during aging are conspicuously absent. Here, we use a transgenic mouse line in which mature dentate granule neurons and CA1 pyramidal neurons are genetically labeled with green fluorescent protein (GFP) to investigate the effects of chronic fluoxetine treatment (18mg/kg/day) on input-specific spine remodeling and mossy fiber structural plasticity in the dorsal and ventral hippocampus in adulthood and middle age. In addition, we examine levels of adult hippocampal neurogenesis, maturation state of dentate granule neurons, neuronal activity and glutamic acid decarboxylase-67 expression in response to chronic fluoxetine in adulthood and middle age. Our studies reveal that while chronic fluoxetine fails to augment adult hippocampal neurogenesis in middle age, the middle-aged hippocampus retains high sensitivity to changes in the dentate gyrus (DG) such as dematuration, hypoactivation, and increased glutamic acid decarboxylase 67 (GAD67) expression. Interestingly, the middle-aged hippocampus shows greater sensitivity to fluoxetine-induced input-specific synaptic remodeling than the hippocampus in adulthood with the stratum-oriens of CA1 exhibiting heightened structural plasticity. The input-specific changes and circuit-level modifications in middle-age were associated with modest enhancement in contextual fear memory precision, anxiety-like behavior and antidepressant-like behavioral responses. PMID:25850664

The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo.

PubMed

Ocampo, Josefina; Chereji, Răzvan V; Eriksson, Peter R; Clark, David J

2016-06-02

Adenosine triphosphate-dependent chromatin remodeling machines play a central role in gene regulation by manipulating chromatin structure. Most genes have a nucleosome-depleted region at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing. We used genome-wide nucleosome sequencing to determine whether these enzymes space nucleosomes differently in vivo We find that CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing. In contrast, ISW2 plays a minor role, limited to transcriptionally inactive genes. Heavily transcribed genes show weak phasing and extreme spacing, either very short or very long, and are depleted of linker histone (H1). Genes with longer spacing are enriched in H1, which directs chromatin folding. We propose that CHD1 directs short spacing, resulting in eviction of H1 and chromatin unfolding, whereas ISW1 directs longer spacing, allowing H1 to bind and condense the chromatin. Thus, competition between the two remodelers to set the spacing on each gene may result in a highly dynamic chromatin structure. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

New predictive model for monitoring bone remodeling.

PubMed

Bougherara, Habiba; Klika, Václav; Marsík, Frantisek; Marík, Ivo A; Yahia, L'hocine

2010-10-01

The aim of this article was to present a new thermodynamic-based model for bone remodeling which is able to predict the functional adaptation of bone in response to changes in both mechanical and biochemical environments. The model was based on chemical kinetics and irreversible thermodynamic principles, in which bone is considered as a self-organizing system that exchanges matter, energy and entropy with its surroundings. The governing equations of the mathematical model have been numerically solved using Matlab software and implemented in ANSYS software using the Finite Element Method. With the aid of this model, the whole inner structure of bone was elucidated. The current model suggested that bone remodeling was a dynamic process which was driven by mechanical loading, metabolic factors and other external contributions. The model clearly indicated that in the absence of mechanical stimulus, the bone was not completely resorbed and reaches a new steady state after about 50% of bone loss. This finding agreed with previous clinical studies. Furthermore, results of virtual computations of bone density in a composite femur showed the development of a dense cortical bone around the medullary canal and a dense trabeculae bone between the femoral head and the calcar region of the medial cortex due to compressive stresses. The comparison of the predicted bone density with the structure of the proximal femur obtained from X-rays and using strain energy density gave credibility to the current model. Copyright 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

21 CFR 184.1375 - Iron, elemental.

Code of Federal Regulations, 2010 CFR

2010-04-01

... microscope, it appears as an amorphous powder free from particles having a crystalline structure. It is... pentacarbonyl. It occurs as a dark gray powder. When viewed under a microscope, it appears as spheres built up...

Atomic force microscopic imaging of Acanthamoeba castellanii and Balamuthia mandrillaris trophozoites and cysts.

PubMed

Aqeel, Yousuf; Siddiqui, Ruqaiyyah; Ateeq, Muhammad; Raza Shah, Muhammad; Kulsoom, Huma; Khan, Naveed Ahmed

2015-01-01

Light microscopy and electron microscopy have been successfully used in the study of microbes, as well as free-living protists. Unlike light microscopy, which enables us to observe living organisms or the electron microscope which provides a two-dimensional image, atomic force microscopy provides a three-dimensional surface profile. Here, we observed two free-living amoebae, Acanthamoeba castellanii and Balamuthia mandrillaris under the phase contrast inverted microscope, transmission electron microscope and atomic force microscope. Although light microscopy was of lower magnification, it revealed functional biology of live amoebae such as motility and osmoregulation using contractile vacuoles of the trophozoite stage, but it is of limited value in defining the cyst stage. In contrast, transmission electron microscopy showed significantly greater magnification and resolution to reveal the ultra-structural features of trophozoites and cysts including intracellular organelles and cyst wall characteristics but it only produced a snapshot in time of a dead amoeba cell. Atomic force microscopy produced three-dimensional images providing detailed topographic description of shape and surface, phase imaging measuring boundary stiffness, and amplitude measurements including width, height and length of A. castellanii and B. mandrillaris trophozoites and cysts. These results demonstrate the importance of the application of various microscopic methods in the biological and structural characterization of the whole cell, ultra-structural features, as well as surface components and cytoskeleton of protist pathogens. © 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.

Impact of specific training and competition on myocardial structure and function in different age ranges of male handball players

PubMed Central

Agrebi, Brahim; Tkatchuk, Vladimir; Hlila, Nawel; Mouelhi, Emna; Belhani, Ali

2015-01-01

Handball activity involves cardiac changes and demands a mixture of both eccentric and concentric remodeling within the heart. This study seeks to explore heart performance and cardiac remodeling likely to define cardiac parameters which influence specific performance in male handball players across different age ranges. Forty three players, with a regular training and competitive background in handball separated into three groups aged on average 11.78±0.41 for youth players aka “schools”, “elite juniors” 15.99±0.81 and “elite adults” 24.46±2.63 years, underwent echocardiography and ECG examinations. Incremental ergocycle and specific field (SFT) tests have also been conducted. With age and regular training and competition, myocardial remodeling in different age ranges exhibit significant differences in dilatation’s parameters between “schools” and “juniors” players, such as the end-diastolic diameter (LVEDD) and the end-systolic diameter of the left ventricle (LVESD), the root of aorta (Ao) and left atrial (LA), while significant increase is observed between “juniors” and “adults” players in the interventricular septum (IVS), the posterior wall thicknesses (PWT) and LV mass index. ECG changes are also noted but NS differences were observed in studied parameters. For incremental maximal test, players demonstrate a significant increase in duration and total work between “schools” and “juniors” and, in total work only, between “juniors” and “seniors”. The SFT shows improvement in performance which ranged between 26.17±1.83 sec to 31.23±2.34 sec respectively from “seniors” to “schools”. The cross-sectional approach used to compare groups with prior hypothesis that there would be differences in exercise performance and cardiac parameters depending on duration of prior handball practice, leads to point out the early cardiac remodeling within the heart as adaptive change. Prevalence of cardiac chamber dilation with less hypertrophy remodeling was found from “schools” to “juniors” while a prevalence of cardiac hypertrophy with less pronounced chamber dilation remodeling was noted later. PMID:26630561

Genetic and environmental variances of bone microarchitecture and bone remodeling markers: a twin study.

PubMed

Bjørnerem, Åshild; Bui, Minh; Wang, Xiaofang; Ghasem-Zadeh, Ali; Hopper, John L; Zebaze, Roger; Seeman, Ego

2015-03-01

All genetic and environmental factors contributing to differences in bone structure between individuals mediate their effects through the final common cellular pathway of bone modeling and remodeling. We hypothesized that genetic factors account for most of the population variance of cortical and trabecular microstructure, in particular intracortical porosity and medullary size - void volumes (porosity), which establish the internal bone surface areas or interfaces upon which modeling and remodeling deposit or remove bone to configure bone microarchitecture. Microarchitecture of the distal tibia and distal radius and remodeling markers were measured for 95 monozygotic (MZ) and 66 dizygotic (DZ) white female twin pairs aged 40 to 61 years. Images obtained using high-resolution peripheral quantitative computed tomography were analyzed using StrAx1.0, a nonthreshold-based software that quantifies cortical matrix and porosity. Genetic and environmental components of variance were estimated under the assumptions of the classic twin model. The data were consistent with the proportion of variance accounted for by genetic factors being: 72% to 81% (standard errors ∼18%) for the distal tibial total, cortical, and medullary cross-sectional area (CSA); 67% and 61% for total cortical porosity, before and after adjusting for total CSA, respectively; 51% for trabecular volumetric bone mineral density (vBMD; all p < 0.001). For the corresponding distal radius traits, genetic factors accounted for 47% to 68% of the variance (all p ≤ 0.001). Cross-twin cross-trait correlations between tibial cortical porosity and medullary CSA were higher for MZ (rMZ  = 0.49) than DZ (rDZ  = 0.27) pairs before (p = 0.024), but not after (p = 0.258), adjusting for total CSA. For the remodeling markers, the data were consistent with genetic factors accounting for 55% to 62% of the variance. We infer that middle-aged women differ in their bone microarchitecture and remodeling markers more because of differences in their genetic factors than differences in their environment. © 2014 American Society for Bone and Mineral Research.

Left Ventricular Architecture, Long-Term Reverse Remodeling, and Clinical Outcome in Mild Heart Failure With Cardiac Resynchronization: Results From the REVERSE Trial.

PubMed

St John Sutton, Martin; Linde, Cecilia; Gold, Michael R; Abraham, William T; Ghio, Stefano; Cerkvenik, Jeffrey; Daubert, Jean-Claude

2017-03-01

This study sought to determine the effects of abnormal left ventricular (LV) architecture on cardiac remodeling and clinical outcomes in mild heart failure (HF). Cardiac resynchronization therapy (CRT) is an established treatment for HF that improves survival in part by favorably remodeling LV architecture. LV shape is a dynamic component of LV architecture on which contractile function depends. Transthoracic 2-dimensional echocardiography was used to quantify changes in LV architecture over 5 years of follow-up of patients with mild HF from the REVERSE study. REVERSE was a prospective study of patients with large hearts (LV end-diastolic dimension ≥55 mm), LV ejection fraction <40%, and QRS duration >120 ms randomly assigned to CRT-ON (n = 419) and CRT-OFF (n = 191). CRT-OFF patients were excluded from this analysis. LV dimensions, volumes, mass index, and LV ejection fraction were calculated. LV architecture was assessed using the sphericity index, as follows: (LV end-diastolic volume)/(4/3 × π × r 3 ) × 100%. LV architecture improved over time and demonstrated significant associations between LV shape, age, sex, and echocardiography metrics. Changes in LV architecture were strongly correlated with changes in LV end-systolic volume index and LV end-diastolic volume index (both p < 0.0001). Sphericity index emerged as a predictor of death and HF hospitalization in spite of the low adverse event rate. A decrease in LV end-systolic volume index >15% occurred in more than two-thirds of patients, which indicates considerable reverse remodeling. We demonstrated that change in LV architecture in patients with mild HF with CRT is associated with structural and functional remodeling. Mean LV filling pressure was elevated, and the inability to lower it was an additional predictor of HF hospitalization or death. (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction [REVERSE]; NCT00271154). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Altered Liver Proteoglycan/Glycosaminoglycan Structure as a Manifestation of Extracellular Matrix Remodeling upon BCG-induced Granulomatosis in Mice.

PubMed

Kim, L B; Shkurupy, V A; Putyatina, A N

2017-01-01

Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host-parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell-cell interaction leading to granuloma development and fibrosis. Later, reduced reserve capacity of the extracellular matrix, development of interstitial fibrosis and granuloma fibrosis can lead to trophic shortage for cells within the granulomas, migration of macrophages out of them, and development of spontaneous necrosis and apoptosis typical of tuberculosis.

Intraoperative Fluorescence Cerebral Angiography by Laser Surgical Microscopy: Comparison With Xenon Microscopy and Simultaneous Observation of Cerebral Blood Flow and Surrounding Structures.

PubMed

Ito, Yuhei; Suzuki, Kyouichi; Ichikawa, Tsuyoshi; Watanabe, Yoichi; Sato, Taku; Sakuma, Jun; Saito, Kiyoshi

2018-06-12

Laser surgical microscopes should enable uniform illumination of the operative field, and require less luminous energy compared with existing xenon surgical microscopes. To examine the utility of laser illumination in fluorescence cerebral angiography. Fluorescein sodium (fluorescein) was used as a fluorescent dye. We first compared the clarity of cerebral blood flow images collected by fluorescence angiography between the laser illumination and xenon illumination methods. We then assessed use of the laser illuminator for simultaneous observation of blood flow and surrounding structures during fluorescence angiography. Furthermore, the study was designed to evaluate usefulness of the thus determined excitation light in clinical cases. Fluorescence angiography using blue light laser for excitation provided higher clarity and contrast blood flow images compared with using blue light generated from a xenon lamp. Further, illumination with excitation light consisting of a combination of 3 types of laser (higher level of blue light, no green light, and lower level of red light) enabled both blood flow and surrounding structures to be observed through the microscope directly by the surgeon. Laser-illuminated fluorescence angiography provides high clarity and contrast images of cerebral blood flow. Further, a laser providing strong blue light and weak red light for excitation light enables simultaneous visual observation of fluorescent blood flow and surrounding structures by the surgeon using a surgical microscope. Overall, these data suggest that laser surgical microscopes are useful for both ordinary operative manipulations and fluorescence angiography.

Fabrication and electric measurements of nanostructures inside transmission electron microscope.

PubMed

Chen, Qing; Peng, Lian-Mao

2011-06-01

Using manipulation holders specially designed for transmission electron microscope (TEM), nanostructures can be characterized, measured, modified and even fabricated in-situ. In-situ TEM techniques not only enable real-time study of structure-property relationships of materials at atomic scale, but also provide the ability to control and manipulate materials and structures at nanoscale. This review highlights in-situ electric measurements and in-situ fabrication and structure modification using manipulation holder inside TEM. Copyright © 2011 Elsevier B.V. All rights reserved.

Robust procedure for creating and characterizing the atomic structure of scanning tunneling microscope tips.

PubMed

Tewari, Sumit; Bastiaans, Koen M; Allan, Milan P; van Ruitenbeek, Jan M

2017-01-01

Scanning tunneling microscopes (STM) are used extensively for studying and manipulating matter at the atomic scale. In spite of the critical role of the STM tip, procedures for controlling the atomic-scale shape of STM tips have not been rigorously justified. Here, we present a method for preparing tips in situ while ensuring the crystalline structure and a reproducibly prepared tip structure up to the second atomic layer. We demonstrate a controlled evolution of such tips starting from undefined tip shapes.

Electronic structure and microscopic model of V(2)GeO(4)F(2)-a quantum spin system with S = 1.

PubMed

Rahaman, Badiur; Saha-Dasgupta, T

2007-07-25

We present first-principles density functional calculations and downfolding studies of the electronic and magnetic properties of the oxide-fluoride quantum spin system V(2)GeO(4)F(2). We discuss explicitly the nature of the exchange paths and provide quantitative estimates of magnetic exchange couplings. A microscopic modelling based on analysis of the electronic structure of this systems puts it in the interesting class of weakly coupled alternating chain S = 1 systems. Based on the microscopic model, we make inferrences about its spin excitation spectra, which needs to be tested by rigorous experimental study.

Enhancing microscopic cascading contributions to higher-order nonlinear-optical responses through forced geometric constraints

NASA Astrophysics Data System (ADS)

Dawson, Nathan J.; Andrews, James H.; Crescimanno, Michael

2012-10-01

We review a model that was developed to take into account all possible microscopic cascading schemes in a single species system out to the fifth order using a self-consistent field approach. This model was designed to study the effects of boundaries in mesoscopic systems with constrained boundaries. These geometric constraints on the macroscopic structure show how the higher-ordered susceptibilities are manipulated by increasing the surface to volume ratio, while the microscopic structure influences the local field from all other molecules in the system. In addition to the review, we discuss methods of modeling real systems of molecules, where efforts are currently underway.

Effects of spaceflight in the adductor longus muscle of rats flown in the Soviet Biosatellite COSMOS 2044. A study employing neural cell adhesion molecule (N-CAM) immunocytochemistry and conventional morphological techniques (light and electron microscopy)

NASA Technical Reports Server (NTRS)

D'Amelio, F.; Daunton, N. G.

1992-01-01

The effects of spaceflight upon the "slow" muscle adductor longus were examined in rats flown in the Soviet Biosatellite COSMOS 2044. The techniques employed included standard methods for light microscopy, neural cell adhesion molecule (N-CAM) immunocytochemistry and electron microscopy. Light microscopic observations revealed myofiber atrophy and segmental necrosis accompanied by cellular infiltrates composed of macrophages, leukocytes and mononuclear cells. Neural cell adhesion molecule immunoreactivity (N-CAM-IR) was seen on the myofiber surface and in regenerating myofibers. Ultrastructural alterations included Z band streaming, disorganization of myofibrillar architecture, sarcoplasmic degradation, extensive segmental necrosis with apparent preservation of the basement membrane, degenerative phenomena of the capillary endothelium and cellular invasion of necrotic areas. Regenerating myofibers were identified by the presence of increased amounts of ribosomal aggregates and chains of polyribosomes associated with myofilaments. The principal electron microscopic changes of the neuromuscular junctions showed axon terminals with a decrease or absence of synaptic vesicles replaced by microtubules and neurofilaments, degeneration of axon terminals, vacant axonal spaces and changes suggestive of axonal sprouting. The present observations suggest that alterations such as myofibrillar disruption and necrosis, muscle regeneration and denervation and synaptic remodeling at the level of the neuromuscular junction may take place during spaceflight.

On the Mechanistic Origins of Toughness in Bone

DTIC Science & Technology

2010-01-01

the cement lines provide the prime sites for microcrack formation, the increased osteon density gives rise to (a) a higher microcrack density, which...organs. The diversity of structures within this family reflects the fine-tuning or adaptation of the structure to its function. In addition , a remarkable...material (16, 20, 21). Unfortunately, excessive remodeling and other aging-related changes to the mus- culoskeletal system increase susceptibility to bone

Nanofat-derived stem cells with platelet-rich fibrin improve facial contour remodeling and skin rejuvenation after autologous structural fat transplantation

PubMed Central

Liang, Zhi-Jie; Chen, Hai; Zhu, Mao-Guang; Xu, Fang-Tian; He, Ning; Wei, Xiao-Juan; Li, Hong-Mian

2017-01-01

Traditional autologous fat transplantation is a common surgical procedure for treating facial soft tissue depression and skin aging. However, the transplanted fat is easily absorbed, reducing the long-term efficacy of the procedure. Here, we examined the efficacy of nanofat-assisted autologous fat structural transplantation. Nanofat-derived stem cells (NFSCs) were isolated, mechanically emulsified, cultured, and characterized. Platelet-rich fibrin (PRF) enhanced proliferation and adipogenic differentiation of NFSCs in vitro. We then compared 62 test group patients with soft tissue depression or signs of aging who underwent combined nanofat, PRF, and autologous fat structural transplantation to control patients (77 cases) who underwent traditional autologous fat transplantation. Facial soft tissue depression symptoms and skin texture were improved to a greater extent after nanofat transplants than after traditional transplants, and the nanofat group had an overall satisfaction rate above 90%. These data suggest that NFSCs function similarly to mesenchymal stem cells and share many of the biological characteristics of traditional fat stem cell cultures. Transplants that combine newly-isolated nanofat, which has a rich stromal vascular fraction (SVF), with PRF and autologous structural fat granules may therefore be a safe, highly-effective, and long-lasting method for remodeling facial contours and rejuvenating the skin. PMID:28978136

Correction of image drift and distortion in a scanning electron microscopy.

PubMed

Jin, P; Li, X

2015-12-01

Continuous research on small-scale mechanical structures and systems has attracted strong demand for ultrafine deformation and strain measurements. Conventional optical microscope cannot meet such requirements owing to its lower spatial resolution. Therefore, high-resolution scanning electron microscope has become the preferred system for high spatial resolution imaging and measurements. However, scanning electron microscope usually is contaminated by distortion and drift aberrations which cause serious errors to precise imaging and measurements of tiny structures. This paper develops a new method to correct drift and distortion aberrations of scanning electron microscope images, and evaluates the effect of correction by comparing corrected images with scanning electron microscope image of a standard sample. The drift correction is based on the interpolation scheme, where a series of images are captured at one location of the sample and perform image correlation between the first image and the consequent images to interpolate the drift-time relationship of scanning electron microscope images. The distortion correction employs the axial symmetry model of charged particle imaging theory to two images sharing with the same location of one object under different imaging fields of view. The difference apart from rigid displacement between the mentioned two images will give distortion parameters. Three-order precision is considered in the model and experiment shows that one pixel maximum correction is obtained for the employed high-resolution electron microscopic system. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Amphibian Metamorphosis: A Sensitive Life Stage to Chemical and Non-chemical Stressors

EPA Science Inventory

Amphibian metamorphosis is a dynamic period of post-embryonic development which transforms the larval anuran into the juvenile. The body structure is remodeled through a variety of processes which may be perturbed by exposure to chemicals as well as other environmental stressors....

Cardiac Remodeling: Endothelial Cells Have More to Say Than Just NO

PubMed Central

Segers, Vincent F. M.; Brutsaert, Dirk L.; De Keulenaer, Gilles W.

2018-01-01

The heart is a highly structured organ consisting of different cell types, including myocytes, endothelial cells, fibroblasts, stem cells, and inflammatory cells. This pluricellularity provides the opportunity of intercellular communication within the organ, with subsequent optimization of its function. Intercellular cross-talk is indispensable during cardiac development, but also plays a substantial modulatory role in the normal and failing heart of adults. More specifically, factors secreted by cardiac microvascular endothelial cells modulate cardiac performance and either positively or negatively affect cardiac remodeling. The role of endothelium-derived small molecules and peptides—for instance NO or endothelin-1—has been extensively studied and is relatively well defined. However, endothelial cells also secrete numerous larger proteins. Information on the role of these proteins in the heart is scattered throughout the literature. In this review, we will link specific proteins that modulate cardiac contractility or cardiac remodeling to their expression by cardiac microvascular endothelial cells. The following proteins will be discussed: IL-6, periostin, tenascin-C, thrombospondin, follistatin-like 1, frizzled-related protein 3, IGF-1, CTGF, dickkopf-3, BMP-2 and−4, apelin, IL-1β, placental growth factor, LIF, WISP-1, midkine, and adrenomedullin. In the future, it is likely that some of these proteins can serve as markers of cardiac remodeling and that the concept of endothelial function and dysfunction might have to be redefined as we learn more about other factors secreted by ECs besides NO. PMID:29695980

Central genes, pathways and modules that regulate bone mass.

PubMed

Quiros-Gonzalez, Isabel; Yadav, Vijay K

2014-11-01

Bones are structures that give the shape and defined features to vertebrates, protect several soft organs and perform multiple endocrine influences on other organs. To achieve these functions bones are first modeled early during life and then constantly remodeled throughout life. The process of bone (re)modeling happens simultaneously at multitude of locations in the skeleton and ensures that vertebrates have a mechanically strong yet a flexible skeleton to the most part of their life. Given the extent of its occurrence in the body, bone remodeling is a highly energy demanding process and is co-ordinated with other physiological processes as diverse as energy metabolism, sleep-wake cycle and reproduction. Neuronal circuits in the brain play a very important role in the coordination of bone remodeling with other organ system functions, and perform this function in sync with environmental and peripheral hormonal cues. In this review, we will focus on the roles of hormonal signals and neural circuits that originate in, or impinge on, the brain in the regulation of bone mass. We will provide herein an updated view of how advances in molecular genetics have refined the neural circuits involved in the regulation of bone mass, from the whole brain level to the specific neuronal populations and their neurotransmitters. This will help to understand the mechanisms whereby vertebrate brain regulates bone mass by fine-tuning metabolic signals that originate in the brain or elsewhere in the body. Copyright © 2014 Elsevier Inc. All rights reserved.

Analysis of the SWI/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation

PubMed Central

Singh, Ajeet Pratap; Archer, Trevor K.

2014-01-01

The regulatory networks of differentiation programs and the molecular mechanisms of lineage-specific gene regulation in mammalian embryos remain only partially defined. We document differential expression and temporal switching of BRG1-associated factor (BAF) subunits, core pluripotency factors and cardiac-specific genes during post-implantation development and subsequent early organogenesis. Using affinity purification of BRG1 ATPase coupled to mass spectrometry, we characterized the cardiac-enriched remodeling complexes present in E8.5 mouse embryos. The relative abundance and combinatorial assembly of the BAF subunits provides functional specificity to Switch/Sucrose NonFermentable (SWI/SNF) complexes resulting in a unique gene expression profile in the developing heart. Remarkably, the specific depletion of the BAF250a subunit demonstrated differential effects on cardiac-specific gene expression and resulted in arrhythmic contracting cardiomyocytes in vitro. Indeed, the BAF250a physically interacts and functionally cooperates with Nucleosome Remodeling and Histone Deacetylase (NURD) complex subunits to repressively regulate chromatin structure of the cardiac genes by switching open and poised chromatin marks associated with active and repressed gene expression. Finally, BAF250a expression modulates BRG1 occupancy at the loci of cardiac genes regulatory regions in P19 cell differentiation. These findings reveal specialized and novel cardiac-enriched SWI/SNF chromatin-remodeling complexes, which are required for heart formation and critical for cardiac gene expression regulation at the early stages of heart development. PMID:24335282

Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency

PubMed Central

Yang, Xuejun; Zhou, Hua; Qu, Huiyan; Liu, Weifang; Huang, Xiaojin; Shun, Yating; He, Liqun

2014-01-01

Objective: To observe the efficacy of Shenxinning Decoction (SXND) in ventricular remodeling in AT1 receptor-knockout (AT1-KO) mice with chronic renal insufficiency (CRI). Materials and Methods: AT1-KO mice modeled with subtotal (5/6) nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN), serum creatinine (SCr), brain natriuretic peptide (BNP), echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF), collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1) of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. Results: AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice's BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. Conclusion: SXND may antagonize the renin–angiotensin system (RAS) and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1. PMID:25097276

Effect of double layers on magnetosphere-ionosphere coupling

NASA Technical Reports Server (NTRS)

Lysak, Robert L.; Hudson, Mary K.

1987-01-01

The Earth's auroral zone contains dynamic processes occurring on scales from the length of an auroral zone field line which characterizes Alfven wave propagation to the scale of microscopic processes which occur over a few Debye lengths. These processes interact in a time-dependent fashion since the current carried by the Alfven waves can excite microscopic turbulence which can in turn provide dissipation of the Alfven wave energy. This review will first describe the dynamic aspects of auroral current structures with emphasis on consequences for models of microscopic turbulence. A number of models of microscopic turbulence will be introduced into a large-scale model of Alfven wave propagation to determine the effect of various models on the overall structure of auroral currents. In particular, the effects of a double layer electric field which scales with the plasma temperature and Debye length is compared with the effect of anomalous resistivity due to electrostatic ion cyclotron turbulence in which the electric field scales with the magnetic field strength. It is found that the double layer model is less diffusive than in the resistive model leading to the possibility of narrow, intense current structures.

FluoroSim: A Visual Problem-Solving Environment for Fluorescence Microscopy

PubMed Central

Quammen, Cory W.; Richardson, Alvin C.; Haase, Julian; Harrison, Benjamin D.; Taylor, Russell M.; Bloom, Kerry S.

2010-01-01

Fluorescence microscopy provides a powerful method for localization of structures in biological specimens. However, aspects of the image formation process such as noise and blur from the microscope's point-spread function combine to produce an unintuitive image transformation on the true structure of the fluorescing molecules in the specimen, hindering qualitative and quantitative analysis of even simple structures in unprocessed images. We introduce FluoroSim, an interactive fluorescence microscope simulator that can be used to train scientists who use fluorescence microscopy to understand the artifacts that arise from the image formation process, to determine the appropriateness of fluorescence microscopy as an imaging modality in an experiment, and to test and refine hypotheses of model specimens by comparing the output of the simulator to experimental data. FluoroSim renders synthetic fluorescence images from arbitrary geometric models represented as triangle meshes. We describe three rendering algorithms on graphics processing units for computing the convolution of the specimen model with a microscope's point-spread function and report on their performance. We also discuss several cases where the microscope simulator has been used to solve real problems in biology. PMID:20431698

Ionic channels in Langmuir-Blodgett films imaged by a scanning tunneling microscope.

PubMed Central

Kolomytkin, O V; Golubok, A O; Davydov, D N; Timofeev, V A; Vinogradova, S A; Tipisev SYa

1991-01-01

The molecular structure of channels formed by gramicidin A in a lipid membrane was imaged by a scanning tunneling microscope operating in air. The mono- and bimolecular films of lipid with gramicidin A were deposited onto a highly oriented pyrolitic graphite substrate by the Langmuir-Blodgett technique. It has been shown that under high concentration gramicidin A molecules can form in lipid films a quasi-regular, densely packed structure. Single gramicidin A molecules were imaged for the first time as well. The cavity of 0.4 +/- 0.05 nm in halfwidth was found on the scanning tunneling microscopy image of the gramicidin A molecule. The results of direct observation obtained by means of scanning tunneling microscope are in good agreement with the known molecular model of gramicidin A. It was shown that gramicidin A molecules can exist in a lipid monolayer as individual molecules or combined into clusters. The results demonstrate that scanning tunneling microscope can be used for high spatial resolution study of ionic channel structure. Images FIGURE 1 FIGURE 2 FIGURE 4 FIGURE 5 PMID:1712239

Application of the AMPLE cluster-and-truncate approach to NMR structures for molecular replacement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bibby, Jaclyn; Keegan, Ronan M.; Mayans, Olga

2013-11-01

Processing of NMR structures for molecular replacement by AMPLE works well. AMPLE is a program developed for clustering and truncating ab initio protein structure predictions into search models for molecular replacement. Here, it is shown that its core cluster-and-truncate methods also work well for processing NMR ensembles into search models. Rosetta remodelling helps to extend success to NMR structures bearing low sequence identity or high structural divergence from the target protein. Potential future routes to improved performance are considered and practical, general guidelines on using AMPLE are provided.

Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood

PubMed Central

Levy, Aaron D.; Omar, Mitchell H.; Koleske, Anthony J.

2014-01-01

Dendritic spines are the receptive contacts at most excitatory synapses in the central nervous system. Spines are dynamic in the developing brain, changing shape as they mature as well as appearing and disappearing as they make and break connections. Spines become much more stable in adulthood, and spine structure must be actively maintained to support established circuit function. At the same time, adult spines must retain some plasticity so their structure can be modified by activity and experience. As such, the regulation of spine stability and remodeling in the adult animal is critical for normal function, and disruption of these processes is associated with a variety of late onset diseases including schizophrenia and Alzheimer’s disease. The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity. While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands. Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults. PMID:25368556

Chromatin Remodeling and Plant Immunity.

PubMed

Chen, W; Zhu, Q; Liu, Y; Zhang, Q

Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance? © 2017 Elsevier Inc. All rights reserved.

Imaging and engineering the nanoscale-domain structure of a Sr0.61Ba0.39Nb2O6 crystal using a scanning force microscope

NASA Astrophysics Data System (ADS)

Terabe, K.; Takekawa, S.; Nakamura, M.; Kitamura, K.; Higuchi, S.; Gotoh, Y.; Gruverman, A.

2002-09-01

We have investigated the ferroelectric domain structure formed in a Sr0.61Ba0.39Nb2O6 single crystal by cooling the crystal through the Curie point. Imaging the etched surface structure using a scanning force microscope (SFM) in both the topographic mode and the piezoresponse mode revealed that a multidomain structure of nanoscale islandlike domains was formed. The islandlike domains could be inverted by applying an appropriate voltage using a conductive SFM tip. Furthermore, a nanoscale periodically inverted-domain structure was artificially fabricated using the crystal which underwent poling treatment.

Mars Life? - Microscopic Tube-like Structures

NASA Technical Reports Server (NTRS)

1996-01-01

This high-resolution scanning electron microscope image shows an unusual tube-like structural form that is less than 1/100th the width of a human hair in size found in meteorite ALH84001, a meteorite believed to be of Martian origin. Although this structure is not part of the research published in the Aug. 16 issue of the journal Science, it is located in a similar carbonate glob in the meteorite. This structure will be the subject of future investigations that could confirm whether or not it is fossil evidence of primitive life on Mars 3.6 billion years ago.

To boldly glow ... applications of laser scanning confocal microscopy in developmental biology.

PubMed

Paddock, S W

1994-05-01

The laser scanning confocal microscope (LSCM) is now established as an invaluable tool in developmental biology for improved light microscope imaging of fluorescently labelled eggs, embryos and developing tissues. The universal application of the LSCM in biomedical research has stimulated improvements to the microscopes themselves and the synthesis of novel probes for imaging biological structures and physiological processes. Moreover the ability of the LSCM to produce an optical series in perfect register has made computer 3-D reconstruction and analysis of light microscope images a practical option.

Application of differential interference contrast with inverted microscopes to the in vitro perfused nephron.

PubMed

Horster, M; Gundlach, H

1979-12-01

The study of in vitro perfused individual nephron segments requires a microscope which provides: (1) easy access to the specimen for measurement of cellular solute flux and voltage; (2) an image with high resolution and contrast; (3) optical sectioning of the object at different levels; and (4) rapid recording of the morphological phenomena. This paper describes an example of commercially available apparatus meeting the above requirements, and illustrates its efficiency. The microscope is of the inverted type (Zeiss IM 35) equipped with differential-interference-contrast (DIC) with a long working distance, and an automatically controlled camera system. The microscopic image exhibits cellular and intercellular details in the unstained transporting mammalian nephron segments despite their tubular structure and great thickness and makes obvious function-structure correlations (e.g. cell volume changes); luminal and contraluminal cell borders are well resolved for controlled microelectrode impalement.

Human fetal ductal plate revisited. I. ductal plate expresses NCAM, KIT, MET, PDGFRA, and neuroendocrine antigens (NSE, chromogranin, synaptophysin, and CD56).

PubMed

Terada, Tadashi

2014-10-01

The molecular mechanisms of ductal plate (DP) development and differentiation (DD) in human fetal livers (HFLs) are unclear. The author immunohistochemically investigated expressions of NCAM, KIT, KIT, PDGFRA, and neuroendocrine antigens in 32 HFLs. The processes of human intrahepatic bile duct (IBD) DD could be categorized into four stages: DP, remodeling DP, remodeled DP, and mature IBD. NCAM was always expressed in DP and remodeling DP, but not in remodeled DP and mature IBD. The biliary elements were positive for cytokeratin (CK)7, 8, 18, and 19. The hepatoblasts were positive for CK8 and CD18, but negative for CK7 and CK19; however, periportal hepatoblasts showed biliary-type CKs (CK7 and CK19). NCAM was always expressed in DP and remodeling DP, but not in remodeled DP and mature IBD. KIT was occasionally (12/32 cases) expressed in DP and remodeling DP, but not in remodeled DP and mature IBD. NCAM expression was also seen in some hepatoblasts and hematopoietic cells and neurons. KIT was also expressed in some hepatoblasts, hematopoietic cells, and mast cells. MET and PDGFRA were strongly expressed in DP, remodeling DP, remodeled DP, and mature IBD. MET and PDGFRA were also strongly expressed in hepatoblasts and hematopoietic cells. MET and PDGFRA were not expressed in portal mesenchyme, portal veins, sinusoids, and hepatic veins. DP showed immunoreactive chromogranin, synaptophysin, neuron-specific enolase (NSE), and CD56. Expressions of chromogranin and CD56 were infrequently seen in remodeling DP. No expressions of these four neuroendocrine antigens were seen in remodeled DP and mature IBD. The nerve fibers were consistently positive for chromogranin, synaptophysin, NSE, and CD56 in the portal mesenchyme in the stages of remodeling DP, remodeled DP, and mature IBDs. The data suggest that NCAM, KIT/stem cell factor-signaling, NSE, hepatocyte growth factor/MET signaling, PDGFα/PDGFRA signaling, chromogranin, synaptophysin, and CD56 play important roles in DD of biliary cells of HFL. They also suggest that the DP cells having neuroendocrine molecules give rise to hepatic stem/progenitor cells. © 2014 Wiley Periodicals, Inc.

Knockdown Brm and Baf170, components of chromatin remodeling complex, facilitates reprogramming of somatic cells

USDA-ARS?s Scientific Manuscript database

The SWI/SNF (SWItch/Sucrose NonFermentable or BAF, Brg/Brahma-associated factors) complexes are epigenetic modifiers of chromatin structure and undergo progressive changes in subunit composition during cellular differentiation. For example, in embryonic stem cells (ESCs) esBAF contains Brg1 and Baf...

MANUAL OF PLANNING STANDARDS FOR SCHOOL BUILDINGS.

ERIC Educational Resources Information Center

New York State Education Dept., Albany.

THIS MANUAL CONTAINS THE REQUIREMENTS AND RECOMMENDATIONS FOR DEVELOPMENT AND DESIGN IN ERECTION, REPAIR, ENLARGEMENT, AND REMODELING OF SCHOOL BUILDINGS, IN TERMS OF HEALTH, COMFORT, AND SAFETY OF PUPILS ATTENDING THE PUBLIC SCHOOLS. SPECIFIC AREAS COVERED BY THIS MANUAL INCLUDE--(1) STRUCTURE AND SAFETY PLANNING, (2) MATERIALS, (3) VISUAL…

Broad Learning System: An Effective and Efficient Incremental Learning System Without the Need for Deep Architecture.

PubMed

Chen, C L Philip; Liu, Zhulin

2018-01-01

Broad Learning System (BLS) that aims to offer an alternative way of learning in deep structure is proposed in this paper. Deep structure and learning suffer from a time-consuming training process because of a large number of connecting parameters in filters and layers. Moreover, it encounters a complete retraining process if the structure is not sufficient to model the system. The BLS is established in the form of a flat network, where the original inputs are transferred and placed as "mapped features" in feature nodes and the structure is expanded in wide sense in the "enhancement nodes." The incremental learning algorithms are developed for fast remodeling in broad expansion without a retraining process if the network deems to be expanded. Two incremental learning algorithms are given for both the increment of the feature nodes (or filters in deep structure) and the increment of the enhancement nodes. The designed model and algorithms are very versatile for selecting a model rapidly. In addition, another incremental learning is developed for a system that has been modeled encounters a new incoming input. Specifically, the system can be remodeled in an incremental way without the entire retraining from the beginning. Satisfactory result for model reduction using singular value decomposition is conducted to simplify the final structure. Compared with existing deep neural networks, experimental results on the Modified National Institute of Standards and Technology database and NYU NORB object recognition dataset benchmark data demonstrate the effectiveness of the proposed BLS.

Microscopic neural image registration based on the structure of mitochondria

NASA Astrophysics Data System (ADS)

Cao, Huiwen; Han, Hua; Rao, Qiang; Xiao, Chi; Chen, Xi

2017-02-01

Microscopic image registration is a key component of the neural structure reconstruction with serial sections of neural tissue. The goal of microscopic neural image registration is to recover the 3D continuity and geometrical properties of specimen. During image registration, various distortions need to be corrected, including image rotation, translation, tissue deformation et.al, which come from the procedure of sample cutting, staining and imaging. Furthermore, there is only certain similarity between adjacent sections, and the degree of similarity depends on local structure of the tissue and the thickness of the sections. These factors make the microscopic neural image registration a challenging problem. To tackle the difficulty of corresponding landmarks extraction, we introduce a novel image registration method for Scanning Electron Microscopy (SEM) images of serial neural tissue sections based on the structure of mitochondria. The ellipsoidal shape of mitochondria ensures that the same mitochondria has similar shape between adjacent sections, and its characteristic of broad distribution in the neural tissue guarantees that landmarks based on the mitochondria distributed widely in the image. The proposed image registration method contains three parts: landmarks extraction between adjacent sections, corresponding landmarks matching and image deformation based on the correspondences. We demonstrate the performance of our method with SEM images of drosophila brain.

Method to deterministically study photonic nanostructures in different experimental instruments.

PubMed

Husken, B H; Woldering, L A; Blum, C; Vos, W L

2009-01-01

We describe an experimental method to recover a single, deterministically fabricated nanostructure in various experimental instruments without the use of artificially fabricated markers, with the aim to study photonic structures. Therefore, a detailed map of the spatial surroundings of the nanostructure is made during the fabrication of the structure. These maps are made using a series of micrographs with successively decreasing magnifications. The graphs reveal intrinsic and characteristic geometric features that can subsequently be used in different setups to act as markers. As an illustration, we probe surface cavities with radii of 65 nm on a silica opal photonic crystal with various setups: a focused ion beam workstation; a scanning electron microscope (SEM); a wide field optical microscope and a confocal microscope. We use cross-correlation techniques to recover a small area imaged with the SEM in a large area photographed with the optical microscope, which provides a possible avenue to automatic searching. We show how both structural and optical reflectivity data can be obtained from one and the same nanostructure. Since our approach does not use artificial grids or markers, it is of particular interest for samples whose structure is not known a priori, like samples created solely by self-assembly. In addition, our method is not restricted to conducting samples.

Imaging Schwarzschild multilayer X-ray microscope

NASA Technical Reports Server (NTRS)

Hoover, Richard B.; Baker, Phillip C.; Shealy, David L.; Core, David B.; Walker, Arthur B. C., Jr.; Barbee, Troy W., Jr.; Kerstetter, Ted

1993-01-01

We have designed, analyzed, fabricated, and tested Schwarzschild multilayer X-ray microscopes. These instruments use flow-polished Zerodur mirror substrates which have been coated with multilayers optimized for maximum reflectivity at normal incidence at 135 A. They are being developed as prototypes for the Water Window Imaging X-Ray Microscope. Ultrasmooth mirror sets of hemlite grade sapphire have been fabricated and they are now being coated with multilayers to reflect soft X-rays at 38 A, within the biologically important 'water window'. In this paper, we discuss the fabrication of the microscope optics and structural components as well as the mounting of the optics and assembly of the microscopes. We also describe the optical alignment, interferometric and visible light testing of the microscopes, present interferometrically measured performance data, and provide the first results of optical imaging tests.

A high-resolution combined scanning laser and widefield polarizing microscope for imaging at temperatures from 4 K to 300 K.

PubMed

Lange, M; Guénon, S; Lever, F; Kleiner, R; Koelle, D

2017-12-01

Polarized light microscopy, as a contrast-enhancing technique for optically anisotropic materials, is a method well suited for the investigation of a wide variety of effects in solid-state physics, as, for example, birefringence in crystals or the magneto-optical Kerr effect (MOKE). We present a microscopy setup that combines a widefield microscope and a confocal scanning laser microscope with polarization-sensitive detectors. By using a high numerical aperture objective, a spatial resolution of about 240 nm at a wavelength of 405 nm is achieved. The sample is mounted on a 4 He continuous flow cryostat providing a temperature range between 4 K and 300 K, and electromagnets are used to apply magnetic fields of up to 800 mT with variable in-plane orientation and 20 mT with out-of-plane orientation. Typical applications of the polarizing microscope are the imaging of the in-plane and out-of-plane magnetization via the longitudinal and polar MOKE, imaging of magnetic flux structures in superconductors covered with a magneto-optical indicator film via the Faraday effect, or imaging of structural features, such as twin-walls in tetragonal SrTiO 3 . The scanning laser microscope furthermore offers the possibility to gain local information on electric transport properties of a sample by detecting the beam-induced voltage change across a current-biased sample. This combination of magnetic, structural, and electric imaging capabilities makes the microscope a viable tool for research in the fields of oxide electronics, spintronics, magnetism, and superconductivity.

A high-resolution combined scanning laser and widefield polarizing microscope for imaging at temperatures from 4 K to 300 K

NASA Astrophysics Data System (ADS)

Lange, M.; Guénon, S.; Lever, F.; Kleiner, R.; Koelle, D.

2017-12-01

Polarized light microscopy, as a contrast-enhancing technique for optically anisotropic materials, is a method well suited for the investigation of a wide variety of effects in solid-state physics, as, for example, birefringence in crystals or the magneto-optical Kerr effect (MOKE). We present a microscopy setup that combines a widefield microscope and a confocal scanning laser microscope with polarization-sensitive detectors. By using a high numerical aperture objective, a spatial resolution of about 240 nm at a wavelength of 405 nm is achieved. The sample is mounted on a 4He continuous flow cryostat providing a temperature range between 4 K and 300 K, and electromagnets are used to apply magnetic fields of up to 800 mT with variable in-plane orientation and 20 mT with out-of-plane orientation. Typical applications of the polarizing microscope are the imaging of the in-plane and out-of-plane magnetization via the longitudinal and polar MOKE, imaging of magnetic flux structures in superconductors covered with a magneto-optical indicator film via the Faraday effect, or imaging of structural features, such as twin-walls in tetragonal SrTiO3. The scanning laser microscope furthermore offers the possibility to gain local information on electric transport properties of a sample by detecting the beam-induced voltage change across a current-biased sample. This combination of magnetic, structural, and electric imaging capabilities makes the microscope a viable tool for research in the fields of oxide electronics, spintronics, magnetism, and superconductivity.

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation.

PubMed

Karki, Rajendra; Kim, Seong-Bin; Kim, Dong-Wook

2013-12-10

Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Mapping human long bone compartmentalisation during ontogeny: a new methodological approach.

PubMed

Cambra-Moo, Oscar; Nacarino Meneses, Carmen; Rodríguez Barbero, Miguel Ángel; García Gil, Orosia; Rascón Pérez, Josefina; Rello-Varona, Santiago; Campo Martín, Manuel; González Martín, Armando

2012-06-01

Throughout ontogeny, human bones undergo differentiation in terms of shape, size and tissue type; this is a complex scenario in which the variations in the tissue compartmentalisation of the cortical bone are still poorly understood. Currently, compartmentalisation is studied using methodologies that oversimplify the bone tissue complexity. Here, we present a new methodological approach that integrates a histological description and a mineral content analysis to study the compartmentalisation of the whole mineralised and non-mineralised tissues (i.e., spatial distribution in long bone sections). This new methodology, based on Geographical Information System (GIS) software, allows us to draw areas of interest (i.e., tracing vectorial shapes which are quantifiable) in raw images that are extracted from microscope and compared them spatially in a semi-automatic and quantitative fashion. As an example of our methodology, we have studied the tibiae from individuals with different age at death (infant, juvenile and adult). The tibia's cortical bone presents a well-formed fibrolamellar bone, in which remodelling is clearly evidenced from early ontogeny, and we discuss the existence of "lines of arrested growth". Concurrent with the histological variation, Raman and FT-IR spectroscopy analyses corroborate that the mineral content in the cortical bone changes differentially. The anterior portion of the tibia remains highly pierced and is less crystalline than the rest of the cortex during growth, which is evidence of more active and continuous remodelling. Finally, while porosity and other "non-mineralised cavities" are largely modified, the mineralised portion and the marrow cavity size persist proportionally during ontogeny. Copyright © 2012 Elsevier Inc. All rights reserved.

A cellular automata model of bone formation.

PubMed

Van Scoy, Gabrielle K; George, Estee L; Opoku Asantewaa, Flora; Kerns, Lucy; Saunders, Marnie M; Prieto-Langarica, Alicia

2017-04-01

Bone remodeling is an elegantly orchestrated process by which osteocytes, osteoblasts and osteoclasts function as a syncytium to maintain or modify bone. On the microscopic level, bone consists of cells that create, destroy and monitor the bone matrix. These cells interact in a coordinated manner to maintain a tightly regulated homeostasis. It is this regulation that is responsible for the observed increase in bone gain in the dominant arm of a tennis player and the observed increase in bone loss associated with spaceflight and osteoporosis. The manner in which these cells interact to bring about a change in bone quality and quantity has yet to be fully elucidated. But efforts to understand the multicellular complexity can ultimately lead to eradication of metabolic bone diseases such as osteoporosis and improved implant longevity. Experimentally validated mathematical models that simulate functional activity and offer eventual predictive capabilities offer tremendous potential in understanding multicellular bone remodeling. Here we undertake the initial challenge to develop a mathematical model of bone formation validated with in vitro data obtained from osteoblastic bone cells induced to mineralize and quantified at 26 days of culture. A cellular automata model was constructed to simulate the in vitro characterization. Permutation tests were performed to compare the distribution of the mineralization in the cultures and the distribution of the mineralization in the mathematical models. The results of the permutation test show the distribution of mineralization from the characterization and mathematical model come from the same probability distribution, therefore validating the cellular automata model. Copyright © 2017 Elsevier Inc. All rights reserved.

Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue: an ex vivo study.

PubMed

Salvatore, Stefano; Leone Roberti Maggiore, Umberto; Athanasiou, Stavros; Origoni, Massimo; Candiani, Massimo; Calligaro, Alberto; Zerbinati, Nicola

2015-08-01

Microablative fractional CO2 laser has been proven to determine tissue remodeling with neoformation of collagen and elastic fibers on atrophic skin. The aim of our study is to evaluate the effects of microablative fractional CO2 laser on postmenopausal women with vulvovaginal atrophy using an ex vivo model. This is a prospective ex vivo cohort trial. Consecutive postmenopausal women with vulvovaginal atrophy managed with pelvic organ prolapse surgical operation were enrolled. After fascial plication, the redundant vaginal edge on one side was treated with CO2 laser (SmartXide2; DEKA Laser, Florence, Italy). Five different CO2 laser setup protocols were tested. The contralateral part of the vaginal wall was always used as control. Excessive vagina was trimmed and sent for histological evaluation to compare treated and nontreated tissues. Microscopic and ultrastructural aspects of the collagenic and elastic components of the matrix were studied, and a specific image analysis with computerized morphometry was performed. We also considered the fine cytological aspects of connective tissue proper cells, particularly fibroblasts. During the study period, five women were enrolled, and 10 vaginal specimens were finally retrieved. Four different settings of CO2 laser were compared. Protocols were tested twice each to confirm histological findings. Treatment protocols were compared according to histological findings, particularly in maximal depth and connective changes achieved. All procedures were uneventful for participants. This study shows that microablative fractional CO2 laser can produce a remodeling of vaginal connective tissue without causing damage to surrounding tissue.

Differentiating characteristic microstructural features of cancerous tissues using Mueller matrix microscope.

PubMed

Wang, Ye; He, Honghui; Chang, Jintao; Zeng, Nan; Liu, Shaoxiong; Li, Migao; Ma, Hui

2015-12-01

Polarized light imaging can provide rich microstructural information of samples, and has been applied to the detections of various abnormal tissues. In this paper, we report a polarized light microscope based on Mueller matrix imaging by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission optical microscope. The maximum errors for the absolute values of Mueller matrix elements are reduced to 0.01 after calibration. This Mueller matrix microscope has been used to examine human cervical and liver cancerous tissues with fibrosis. Images of the transformed Mueller matrix parameters provide quantitative assessment on the characteristic features of the pathological tissues. Contrast mechanism of the experimental results are backed up by Monte Carlo simulations based on the sphere-cylinder birefringence model, which reveal the relationship between the pathological features in the cancerous tissues at the cellular level and the polarization parameters. Both the experimental and simulated data indicate that the microscopic transformed Mueller matrix parameters can distinguish the breaking down of birefringent normal tissues for cervical cancer, or the formation of birefringent surrounding structures accompanying the inflammatory reaction for liver cancer. With its simple structure, fast measurement and high precision, polarized light microscope based on Mueller matrix shows a good diagnosis application prospect. Copyright © 2015 Elsevier Ltd. All rights reserved.

Local Order-Disorder Transition Driving by Structural Heterogeneity in a Benzyl Functionalized Ionic Liquid.

PubMed

Faria, Luiz F O; Paschoal, Vitor H; Lima, Thamires A; Ferreira, Fabio F; Freitas, Rafael S; Ribeiro, Mauro C C

2017-10-26

A local order-disorder transition has been disclosed in the thermophysical behavior of the ionic liquid 1-benzyl-3-methylimidazolium dicyanamide, [Bzmim][N(CN) 2 ], and its microscopic nature revealed by spectroscopic techniques. Differential scanning calorimetry and specific heat measurements show a thermal event of small enthalpy variation taking place in the range 250-260 K, which is not due to crystallization or melting. Molecular dynamic simulations and X-ray diffraction measurements have been used to discuss the segregation of domains in the liquid structure of [Bzmim][N(CN) 2 ]. Raman and NMR spectroscopy measurements as a function of temperature indicate that the microscopic origin of the event observed in the calorimetric measurements comes from structural rearrangement involving the benzyl group. The results indicate that the characteristic structural heterogeneity allow for rearrangements within local domains implying the good glass-forming ability for the low viscosity ionic liquid [Bzmim][N(CN) 2 ]. This work sheds light on our understanding of the microscopic origin behind complex thermal behavior of ionic liquids.

Hierarchical recruitment of ribosomal proteins and assembly factors remodels nucleolar pre-60S ribosomes.

PubMed

Biedka, Stephanie; Micic, Jelena; Wilson, Daniel; Brown, Hailey; Diorio-Toth, Luke; Woolford, John L

2018-04-24

Ribosome biogenesis involves numerous preribosomal RNA (pre-rRNA) processing events to remove internal and external transcribed spacer sequences, ultimately yielding three mature rRNAs. Removal of the internal transcribed spacer 2 spacer RNA is the final step in large subunit pre-rRNA processing and begins with endonucleolytic cleavage at the C 2 site of 27SB pre-rRNA. C 2 cleavage requires the hierarchical recruitment of 11 ribosomal proteins and 14 ribosome assembly factors. However, the function of these proteins in C 2 cleavage remained unclear. In this study, we have performed a detailed analysis of the effects of depleting proteins required for C 2 cleavage and interpreted these results using cryo-electron microscopy structures of assembling 60S subunits. This work revealed that these proteins are required for remodeling of several neighborhoods, including two major functional centers of the 60S subunit, suggesting that these remodeling events form a checkpoint leading to C 2 cleavage. Interestingly, when C 2 cleavage is directly blocked by depleting or inactivating the C 2 endonuclease, assembly progresses through all other subsequent steps. © 2018 Biedka et al.

Long-term healing of mildly cross-linked decellularized bovine pericardial aortic patch.

PubMed

Umashankar, P R; Sabareeswaran, A; Shenoy, Sachin J

2017-10-01

Glutaraldehyde treated bovine pericardium is extensively used in cardiovascular surgery. However, frequent occurrence of failure modes, such as calcification and structural failure, has hard pressed the need for finding an alternate technology. Decellularized bovine pericardium is an emerging technology. Mildly cross-linked decellularized bovine pericardium promotes positive remodeling with insignificant calcification and acute inflammation. In the present study, mildly cross-linked decellularized bovine pericardium was evaluated as a cardiovascular patch by studying mechanical strength as well as graft remodeling, resistance to calcific degeneration and inflammatory response using long duration porcine aortic implantation. It was observed that decellularized bovine pericardium, although thinner and less elastic had equivalent tensile properties such as tensile strength and stiffness when compared to commercially available glutaraldehyde-treated bovine pericardium. It showed the potential for site appropriate remodeling evidenced by host cell incorporation, thinner neointima, graft degradation, and neocollagenisation making it suitable for vascular patch application, whereas glutaraldehyde-treated pericardium failed to integrate with host tissue through timely degradation and host cell incorporation or neocollagenization. Conversely, it elicited persistent acute inflammation and produced calcification. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2145-2152, 2017. © 2016 Wiley Periodicals, Inc.