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Sample records for tissue reference signal

  1. Qualitative analysis of intracranial CSF flow on cine-MR imaging, with special reference to signal ratio of CSF to fat tissue

    International Nuclear Information System (INIS)

    Kadowaki, Chikafusa; Hara, Mitsuhiro; Numoto, Mitsuo; Takeuchi, Kazuo; Saito, Isamu

    1993-01-01

    Cine magnetic resonance images (MR) dramatically demonstrate the pulsatile flow of cerebrospinal fluid (CSF) stimulated by the pulsatile motion of the brain following cardiac pulsation. Reduced signal intensity, frequently observed especially in the aqueduct of Sylvius, the third ventricle and the fourth ventricle, is believed to reflect the pulsatile motion of the CSF. Qualitative analysis of MR signal intensity of CSF on each cine frame is compared with CSF flow within the ventricles on real-time cine MR images. While the chronological changes in signal intensities of CSF within the ventricles show only marginal changes in signal intensity in the third ventricle related to downward flow of CSF passing through the foramen of Monro during the early stage of cardiac systole, these changes are thought to have no significant correlation with the CSF flow in the CSF pathway. The chronological changes in relative signal ratios, SR [signal intensities of CSF/signal intensities of fat] can show CSF flow and turbulence within the ventricles. Under normal conditions, within the third ventricle the SR decreases due to pulsatile CSF flow through the foramen of Monro during the early stage of cardiac systole, and decreases because of the flow of CSF from the anterior to the posterior part of the third ventricle, the downward flow of CSF through the aqueduct leads to a lower SR during cardiac diastole. These changes in the fourth ventricle are stimulated by the changes in SR in the third ventricle. The new method of analyzing chronological changes in the relative MR signal ratio of CSF to fat [SR] has the distinct advantage of providing an accurate evaluation of CSF dynamics, and it provides us with important diagnostic information leading to clarification of the pathophysiology of CSF dynamics. (author)

  2. Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2013-12-01

    Full Text Available Real-time quantitative PCR (qRT-PCR is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2 in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

  3. Reference analysis of the signal + background model in counting experiments

    Science.gov (United States)

    Casadei, D.

    2012-01-01

    The model representing two independent Poisson processes, labelled as ``signal'' and ``background'' and both contributing additively to the total number of counted events, is considered from a Bayesian point of view. This is a widely used model for the searches of rare or exotic events in presence of a background source, as for example in the searches performed by high-energy physics experiments. In the assumption of prior knowledge about the background yield, a reference prior is obtained for the signal alone and its properties are studied. Finally, the properties of the full solution, the marginal reference posterior, are illustrated with few examples.

  4. Suitable reference tissues for quantitative susceptibility mapping of the brain.

    Science.gov (United States)

    Straub, Sina; Schneider, Till M; Emmerich, Julian; Freitag, Martin T; Ziener, Christian H; Schlemmer, Heinz-Peter; Ladd, Mark E; Laun, Frederik B

    2017-07-01

    Since quantitative susceptibility mapping (QSM) quantifies magnetic susceptibility relative to a reference value, a suitable reference tissue has to be available to compare different subjects and stages of disease. To find such a suitable reference tissue for QSM of the brain, melanoma patients with and without brain metastases were measured. Twelve reference regions were chosen and assessed for stability of susceptibility values with respect to multiple intra-individual and inter-individual measurements, age, and stage of disease. Cerebrospinal fluid (CSF), the internal capsule and one region in the splenium of the corpus callosum are the regions with the smallest standard deviations of the mean susceptibility value. The mean susceptibility is 0.010 ± 0.014 ppm for CSF in the atrium of the lateral ventricles (csf post ), -0.060 ± 0.019 ppm for the posterior limb of the internal capsule (ci2), and -0.008 ± 0.019 ppm for the splenium of the corpus callosum. csf post and ci2 show nearly no dependence on age or stage of disease, whereas some other regions, e.g., the red nucleus, show moderate dependence on age or disease. The internal capsule and CSF appear to be the most suitable reference regions for QSM of the brain in the melanoma patients studied. Both showed virtually no dependence on age or disease and small variations among patients. Magn Reson Med 78:204-214, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  5. Multivariate reference technique for quantitative analysis of fiber-optic tissue Raman spectroscopy.

    Science.gov (United States)

    Bergholt, Mads Sylvest; Duraipandian, Shiyamala; Zheng, Wei; Huang, Zhiwei

    2013-12-03

    We report a novel method making use of multivariate reference signals of fused silica and sapphire Raman signals generated from a ball-lens fiber-optic Raman probe for quantitative analysis of in vivo tissue Raman measurements in real time. Partial least-squares (PLS) regression modeling is applied to extract the characteristic internal reference Raman signals (e.g., shoulder of the prominent fused silica boson peak (~130 cm(-1)); distinct sapphire ball-lens peaks (380, 417, 646, and 751 cm(-1))) from the ball-lens fiber-optic Raman probe for quantitative analysis of fiber-optic Raman spectroscopy. To evaluate the analytical value of this novel multivariate reference technique, a rapid Raman spectroscopy system coupled with a ball-lens fiber-optic Raman probe is used for in vivo oral tissue Raman measurements (n = 25 subjects) under 785 nm laser excitation powers ranging from 5 to 65 mW. An accurate linear relationship (R(2) = 0.981) with a root-mean-square error of cross validation (RMSECV) of 2.5 mW can be obtained for predicting the laser excitation power changes based on a leave-one-subject-out cross-validation, which is superior to the normal univariate reference method (RMSE = 6.2 mW). A root-mean-square error of prediction (RMSEP) of 2.4 mW (R(2) = 0.985) can also be achieved for laser power prediction in real time when we applied the multivariate method independently on the five new subjects (n = 166 spectra). We further apply the multivariate reference technique for quantitative analysis of gelatin tissue phantoms that gives rise to an RMSEP of ~2.0% (R(2) = 0.998) independent of laser excitation power variations. This work demonstrates that multivariate reference technique can be advantageously used to monitor and correct the variations of laser excitation power and fiber coupling efficiency in situ for standardizing the tissue Raman intensity to realize quantitative analysis of tissue Raman measurements in vivo, which is particularly appealing in

  6. Calcium as a signal integrator in developing epithelial tissues.

    Science.gov (United States)

    Brodskiy, Pavel A; Zartman, Jeremiah J

    2018-05-16

    Decoding how tissue properties emerge across multiple spatial and temporal scales from the integration of local signals is a grand challenge in quantitative biology. For example, the collective behavior of epithelial cells is critical for shaping developing embryos. Understanding how epithelial cells interpret a diverse range of local signals to coordinate tissue-level processes requires a systems-level understanding of development. Integration of multiple signaling pathways that specify cell signaling information requires second messengers such as calcium ions. Increasingly, specific roles have been uncovered for calcium signaling throughout development. Calcium signaling regulates many processes including division, migration, death, and differentiation. However, the pleiotropic and ubiquitous nature of calcium signaling implies that many additional functions remain to be discovered. Here we review a selection of recent studies to highlight important insights into how multiple signals are transduced by calcium transients in developing epithelial tissues. Quantitative imaging and computational modeling have provided important insights into how calcium signaling integration occurs. Reverse-engineering the conserved features of signal integration mediated by calcium signaling will enable novel approaches in regenerative medicine and synthetic control of morphogenesis.

  7. Exploring valid reference genes for quantitative real - time rt - pce studies of hydrogenperoxide signaling in arabidopsis

    International Nuclear Information System (INIS)

    Zhou, H.; Han, B.; Xie, Y.; Zhang, J.; Shen, W.

    2015-01-01

    Hydrogen peroxide (H/sub 2/O/sub 2/ ) acts as a signaling molecule modulating the expression of various genes in plants. However, the reference gene(s) used for gene expression analysis of H/sub 2/O/sub 2/ signaling is still arbitrary. A reliable result obtained by quantitative real-time RT-PCR (RT-qPCR) highly depends on accurate transcript normalization using stably expressed reference genes, whereas the inaccurate normalization could easily lead to the false conclusions. In this report, by using geNorm and NormFinder algorithms, 12 candidate reference genes were evaluated and compared in root and shoot tissues of Arabidopsis upon different doses of H/sub 2/O/sub 2/. The results revealed that, in our experimental conditions, three novel reference genes (TIP41-like, UKN, and UBC21) were identified and validated as suitable reference genes for RT-qPCR normalization in both root and shoot tissues under oxidative stress. This conclusion was further confirmed by publicly available microarray data of methyl viologen and drought stress. In comparison with a single reference gene (EF-1a), the expression pattern of ZAT12 modulated by H/sub 2/O/sub 2/, when using TIP41-like, UKN, and UBC21 as multiple reference gene(s), was similar with the previous reports by using northern blotting. Thus, we proposed that these three reference genes might be good candidates for other researchers to include in their reference gene validation in gene expression studies under H/sub 2/O/sub 2/ related oxidative stress. (author)

  8. Tissue microarrays and their use for preparation of reference slides ...

    African Journals Online (AJOL)

    Use of Tissue array was first applied in 1998, and has received a significant amount of attention from the research community ever since. In this technique, a large number (up to 1000) of cylindrical tissue core extracted from \\"donor\\" paraffin block are deposited into \\"recipient\\" block. The aim was modification of the ...

  9. Reference Models for Multi-Layer Tissue Structures

    Science.gov (United States)

    2016-09-01

    function of multi-layer tissues (etiology and management of pressure ulcers ). What was the impact on other disciplines? As part of the project, a data...simplification to develop cost -effective models of surface manipulation of multi-layer tissues. Deliverables. Specimen- (or subject) and region-specific...simplification to develop cost -effective models of surgical manipulation. Deliverables. Specimen-specific surrogate models of upper legs confirmed against data

  10. Designs of precoding for LTE TDD using cell specific reference signals

    DEFF Research Database (Denmark)

    Sun, Fan; Lu, Lu; Sørensen, Troels Bundgaard

    2010-01-01

    We design non-codebook-based Multiple-Input Multiple-Output (MIMO) precoding schemes using multiple cell-specific reference signals patterns for the time division duplex (TDD) mode of LTE, where channel reciprocity can be exploited. Previously proposed non-codebookbased precoding schemes typically...... use UE specific reference signals for demodulation. Cell specific reference signals are however always allocated for the transmission of common control signalling, mobility measurements and downlink channel quality measurements. In order to save the resources occupied by UE specific reference signals...

  11. Auditory Warnings, Signal-Referent Relations, and Natural Indicators: Re-Thinking Theory and Application

    Science.gov (United States)

    Petocz, Agnes; Keller, Peter E.; Stevens, Catherine J.

    2008-01-01

    In auditory warning design the idea of the strength of the association between sound and referent has been pivotal. Research has proceeded via constructing classification systems of signal-referent associations and then testing predictions about ease of learning of different levels of signal-referent relation strength across and within different…

  12. Astrocyte calcium signal and gliotransmission in human brain tissue.

    Science.gov (United States)

    Navarrete, Marta; Perea, Gertrudis; Maglio, Laura; Pastor, Jesús; García de Sola, Rafael; Araque, Alfonso

    2013-05-01

    Brain function is recognized to rely on neuronal activity and signaling processes between neurons, whereas astrocytes are generally considered to play supportive roles for proper neuronal function. However, accumulating evidence indicates that astrocytes sense and control neuronal and synaptic activity, indicating that neuron and astrocytes reciprocally communicate. While this evidence has been obtained in experimental animal models, whether this bidirectional signaling between astrocytes and neurons occurs in human brain remains unknown. We have investigated the existence of astrocyte-neuron communication in human brain tissue, using electrophysiological and Ca(2+) imaging techniques in slices of the cortex and hippocampus obtained from biopsies from epileptic patients. Cortical and hippocampal human astrocytes displayed spontaneous Ca(2+) elevations that were independent of neuronal activity. Local application of transmitter receptor agonists or nerve electrical stimulation transiently elevated Ca(2+) in astrocytes, indicating that human astrocytes detect synaptic activity and respond to synaptically released neurotransmitters, suggesting the existence of neuron-to-astrocyte communication in human brain tissue. Electrophysiological recordings in neurons revealed the presence of slow inward currents (SICs) mediated by NMDA receptor activation. The frequency of SICs increased after local application of ATP that elevated astrocyte Ca(2+). Therefore, human astrocytes are able to release the gliotransmitter glutamate, which affect neuronal excitability through activation of NMDA receptors in neurons. These results reveal the existence of reciprocal signaling between neurons and astrocytes in human brain tissue, indicating that astrocytes are relevant in human neurophysiology and are involved in human brain function.

  13. Suitability of stratagene reference RNA for analysis of lymphoid tissues

    DEFF Research Database (Denmark)

    Dybkaer, Karen; Zhou, Guimei; Iqbal, Javeed

    2004-01-01

    acceptable gene coverage to serve as a comprehensive standard for gene expression profiling of lymphoid tissues. Our lymphoid standard was prepared from thymus, spleen, tonsil, and cell lines representing immature B cells, plasma cells, and natural killer (NK) cells, thus covering the entire spectrum...... of lymphoid cells and most stromal elements present in specialized lymphoid tissues. The two standards were co-hybridized on oligonucleotide microarrays containing 17,260 genes, and both had fluorescence intensities above background for approximately 85% of the genes. Despite the limited representation...... of lymphoid cells in the Stratagene standard, only 4.2% genes exhibited expression differences greater than 2-fold including only 0.35% with differences greater than 4-fold. Although the lymphoid standard reflected a more comprehensive representation of immune system-associated genes, the Stratagene standard...

  14. Compact biomedical pulsed signal generator for bone tissue stimulation

    Science.gov (United States)

    Kronberg, James W.

    1993-01-01

    An apparatus for stimulating bone tissue for stimulating bone growth or treating osteoporosis by applying directly to the skin of the patient an alternating current electrical signal comprising wave forms known to simulate the piezoelectric constituents in bone. The apparatus may, by moving a switch, stimulate bone growth or treat osteoporosis, as desired. Based on low-power CMOS technology and enclosed in a moisture-resistant case shaped to fit comfortably, two astable multivibrators produce the desired waveforms. The amplitude, pulse width and pulse frequency, and the subpulse width and subpulse frequency of the waveforms are adjustable. The apparatus, preferably powered by a standard 9-volt battery, includes signal amplitude sensors and warning signals indicate an output is being produced and the battery needs to be replaced.

  15. A method to obtain reference images for evaluation of ultrasonic tissue characterization techniques

    DEFF Research Database (Denmark)

    Jensen, M.S.; Wilhjelm, Jens E.; Sahl, B.

    2002-01-01

    of the macroscopic photograph, due to the histological preparation process. The histological information was "mapped back" into the format of the ultrasound images the following way: On the macroscopic images, outlines were drawn manually which defined the border of the tissue. These outlines were superimposed...... of the various tissue types. Specifically, the macroscopic image revealed the borders between the different tissues, while the histological image identified the four tissue types. A set of 12 reference images based on modified macroscopic outlines was created. The overlap between the ultrasound images...... and the macroscopic images-which are the geometrical basis for the final reference images-was between 77% and 93%. A set of 12 reference images spaced 2.5 mm, identifying spatial location of four different tissue types in porcine muscle has been created. With the reference images, it is possible to quantitatively...

  16. Reference hearing threshold levels for short duration signals

    DEFF Research Database (Denmark)

    Poulsen, Torben; Legarth, Søren Vase

    2008-01-01

    for the determination of reference hearing threshold levels. The results are given as peak-to-peak equivalent threshold sound pressure levels (peETSPL). The results are in good agreement with other sparse results from literature and are part of the basis for the ISO 389-6 standard from 2007....

  17. Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies

    NARCIS (Netherlands)

    Klumpers, Ursula M. H.; Veltman, Dick J.; Boellaard, Ronald; Comans, Emile F.; Zuketto, Cassandra; Yaqub, Maqsood; Mourik, Jurgen E. M.; Lubberink, Mark; Hoogendijk, Witte J. G.; Lammertsma, Adriaan A.

    2008-01-01

    A single-tissue compartment model with plasma input is the established method for analysing [(11)C]flumazenil ([(11)C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been

  18. Tuning Cell and Tissue Development by Combining Multiple Mechanical Signals.

    Science.gov (United States)

    Sinha, Ravi; Verdonschot, Nico; Koopman, Bart; Rouwkema, Jeroen

    2017-10-01

    Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.

  19. Characterization of tissue biomechanics and mechanical signaling in uterine leiomyoma☆

    Science.gov (United States)

    Norian, John M.; Owen, Carter M.; Taboas, Juan; Korecki, Casey; Tuan, Rocky; Malik, Minnie; Catherino, William H.; Segars, James H.

    2012-01-01

    Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stiff, disordered extracellular matrix (ECM). Mechanical stress is a critical determinant of excessive ECM deposition and increased mechanical stress has been shown to be involved in tumorigenesis. Here we tested the viscoelastic properties of leiomyoma and characterized dynamic and static mechanical signaling in leiomyoma cells using three approaches, including measurement of active RhoA. We found that the peak strain and pseudo-dynamic modulus of leiomyoma tissue was significantly increased relative to matched myometrium. In addition, leiomyoma cells demonstrated an attenuated response to applied cyclic uniaxial strain and to variation in substrate stiffness, relative to myometrial cells. However, on a flexible pronectin-coated silicone substrate, basal levels and lysophosphatidic acid-stimulated levels of activated RhoA were similar between leiomyoma and myometrial cells. In contrast, leiomyoma cells plated on a rigid polystyrene substrate had elevated levels of active RhoA, compared to myometrial cells. The results indicate that viscoelastic properties of the ECM of leiomyoma contribute significantly to the tumor’s inherent stiffness and that leiomyoma cells have an attenuated sensitivity to mechanical cues. The findings suggest there may be a fundamental alteration in the communication between the external mechanical environment (extracellular forces) and reorganization of the actin cytoskeleton mediated by RhoA in leiomyoma cells. Additional research will be needed to elucidate the mechanism(s) responsible for the attenuated mechanical signaling in leiomyoma cells. PMID:21983114

  20. SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods.

    Science.gov (United States)

    Schuitemaker, Alie; van Berckel, Bart N M; Kropholler, Marc A; Veltman, Dick J; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A; Boellaard, Ronald

    2007-05-01

    (R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to interobserver variation. In addition, results are only obtained for predefined areas and (unexpected) signals in undefined areas may be missed. On the other hand, standard pharmacokinetic models are too sensitive to noise to calculate (R)-[11C]PK11195 binding on a voxel-by-voxel basis. Linearised versions of both plasma input and reference tissue models have been described, and these are more suitable for parametric imaging. The purpose of this study was to compare the performance of these plasma input and reference tissue parametric methods on the outcome of statistical parametric mapping (SPM) analysis of (R)-[11C]PK11195 binding. Dynamic (R)-[11C]PK11195 PET scans with arterial blood sampling were performed in 7 younger and 11 elderly healthy subjects. Parametric images of volume of distribution (Vd) and binding potential (BP) were generated using linearised versions of plasma input (Logan) and reference tissue (Reference Parametric Mapping) models. Images were compared at the group level using SPM with a two-sample t-test per voxel, both with and without proportional scaling. Parametric BP images without scaling provided the most sensitive framework for determining differences in (R)-[11C]PK11195 binding between younger and elderly subjects. Vd images could only demonstrate differences in (R)-[11C]PK11195 binding when analysed with proportional scaling due to intersubject variation in K1/k2 (blood-brain barrier transport and non-specific binding).

  1. Identification of reference genes and validation for gene expression studies in diverse axolotl (Ambystoma mexicanum) tissues.

    Science.gov (United States)

    Guelke, Eileen; Bucan, Vesna; Liebsch, Christina; Lazaridis, Andrea; Radtke, Christine; Vogt, Peter M; Reimers, Kerstin

    2015-04-10

    For the precise quantitative RT-PCR normalization a set of valid reference genes is obligatory. Moreover have to be taken into concern the experimental conditions as they bias the regulation of reference genes. Up till now, no reference targets have been described for the axolotl (Ambystoma mexicanum). In a search in the public database SalSite for genetic information of the axolotl we identified fourteen presumptive reference genes, eleven of which were further tested for their gene expression stability. This study characterizes the expressional patterns of 11 putative endogenous control genes during axolotl limb regeneration and in an axolotl tissue panel. All 11 reference genes showed variable expression. Strikingly, ACTB was to be found most stable expressed in all comparative tissue groups, so we reason it to be suitable for all different kinds of axolotl tissue-type investigations. Moreover do we suggest GAPDH and RPLP0 as suitable for certain axolotl tissue analysis. When it comes to axolotl limb regeneration, a validated pair of reference genes is ODC and RPLP0. With these findings, new insights into axolotl gene expression profiling might be gained. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Validation of reference genes in Solenopsis invicta in different developmental stages, castes and tissues.

    Directory of Open Access Journals (Sweden)

    Daifeng Cheng

    Full Text Available To accurately assess gene expression levels, it is essential to normalize real-time quantitative PCR (RT-qPCR data with suitable internal reference genes. For the red imported fire ant, Solenopsis invicta, reliable reference genes to assess the transcript expression levels of the target genes have not been previously investigated. In this study, we examined the expression levels of five candidate reference genes (rpl18, ef1-beta, act, GAPDH, and tbp in different developmental stages, castes and tissues of S. invicta. To evaluate the suitability of these genes as endogenous controls, three software-based approaches (geNorm, BestKeeper and NormFinder and one web-based comprehensive tool (RefFinder were used to analyze and rank the tested genes. Furthermore, the optimal number of reference gene(s was determined by the pairwise variation value. Our data showed that two of the five candidate genes, rpl18 and ef1-beta, were the most suitable reference genes because they have the most stable expression among different developmental stages, castes and tissues in S. invicta. Although widely used as reference gene in other species, in S. invicta the act gene has high variation in expression and was consequently excluded as a reliable reference gene. The two validated reference genes, rpl18 and ef1-beta, can be widely used for quantification of target gene expression with RT-qPCR technology in S. invicta.

  3. A protein-based set of reference markers for liver tissues and hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Sun, Stella; Yi, Xin; Poon, Ronnie TP; Yeung, Chun; Day, Philip JR; Luk, John M

    2009-01-01

    During the last decade, investigations have focused on revealing genes or proteins that are involved in HCC carcinogenesis using either genetic or proteomic techniques. However, these studies are overshadowed by a lack of good internal reference standards. The need to identify 'housekeeping' markers, whose expression is stable in various experimental and clinical conditions, is therefore of the utmost clinical relevance in quantitative studies. This is the first study employed 2-DE analysis to screen for potential reference markers and aims to correlate the abundance of these proteins with their level of transcript expression. A Chinese cohort of 224 liver tissues samples (105 cancerous, 103 non-tumourous cirrhotic, and 16 normal) was profiled using 2-DE analysis. Expression of the potential reference markers was confirmed by western blot, immunohistochemistry and real-time quantitative PCR. geNorm algorithm was employed for gene stability measure of the identified reference markers. The expression levels of three protein markers beta-actin (ACTB), heat shock protein 60 (HSP60), and protein disulphide isomerase (PDI) were found to be stable using p-values (p > 0.99) as a ranking tool in all 224 human liver tissues examined by 2-DE analysis. Of high importance, ACTB and HSP 60 were successfully validated at both protein and mRNA levels in human hepatic tissues by western blot, immunohistochemistry and real-time quantitative PCR. In addition, no significant correlation of these markers with any clinicopathological features of HCC and cirrhosis was found. Gene stability measure of these two markers with other conventionally applied housekeeping genes was assessed by the geNorm algorithm, which ranked ACTB and HSP60 as the most stable genes among this cohort of clinical samples. Our findings identified 2 reference markers that exhibited stable expression across human liver tissues with different conditions thus should be regarded as reliable reference

  4. Automated segmentation of reference tissue for prostate cancer localization in dynamic contrast enhanced MRI

    Science.gov (United States)

    Vos, Pieter C.; Hambrock, Thomas; Barentsz, Jelle O.; Huisman, Henkjan J.

    2010-03-01

    For pharmacokinetic (PK) analysis of Dynamic Contrast Enhanced (DCE) MRI the arterial input function needs to be estimated. Previously, we demonstrated that PK parameters have a significant better discriminative performance when per patient reference tissue was used, but required manual annotation of reference tissue. In this study we propose a fully automated reference tissue segmentation method that tackles this limitation. The method was tested with our Computer Aided Diagnosis (CADx) system to study the effect on the discriminating performance for differentiating prostate cancer from benign areas in the peripheral zone (PZ). The proposed method automatically segments normal PZ tissue from DCE derived data. First, the bladder is segmented in the start-to-enhance map using the Otsu histogram threshold selection method. Second, the prostate is detected by applying a multi-scale Hessian filter to the relative enhancement map. Third, normal PZ tissue was segmented by threshold and morphological operators. The resulting segmentation was used as reference tissue to estimate the PK parameters. In 39 consecutive patients carcinoma, benign and normal tissue were annotated on MR images by a radiologist and a researcher using whole mount step-section histopathology as reference. PK parameters were computed for each ROI. Features were extracted from the set of ROIs using percentiles to train a support vector machine that was used as classifier. Prospective performance was estimated by means of leave-one-patient-out cross validation. A bootstrap resampling approach with 10,000 iterations was used for estimating the bootstrap mean AUCs and 95% confidence intervals. In total 42 malignant, 29 benign and 37 normal regions were annotated. For all patients, normal PZ was successfully segmented. The diagnostic accuracy obtained for differentiating malignant from benign lesions using a conventional general patient plasma profile showed an accuracy of 0.64 (0.53-0.74). Using the

  5. Evaluation of suitable reference genes for gene expression studies in bovine muscular tissue

    Directory of Open Access Journals (Sweden)

    Dunner Susana

    2008-09-01

    Full Text Available Abstract Background Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RTqPCR is a technique used to measure mRNA species copy number as a way to determine key genes involved in different biological processes. However, the expression level of these key genes may vary among tissues or cells not only as a consequence of differential expression but also due to different factors, including choice of reference genes to normalize the expression levels of the target genes; thus the selection of reference genes is critical for expression studies. For this purpose, ten candidate reference genes were investigated in bovine muscular tissue. Results The value of stability of ten candidate reference genes included in three groups was estimated: the so called 'classical housekeeping' genes (18S, GAPDH and ACTB, a second set of genes used in expression studies conducted on other tissues (B2M, RPII, UBC and HMBS and a third set of novel genes (SF3A1, EEF1A2 and CASC3. Three different statistical algorithms were used to rank the genes by their stability measures as produced by geNorm, NormFinder and Bestkeeper. The three methods tend to agree on the most stably expressed genes and the least in muscular tissue. EEF1A2 and HMBS followed by SF3A1, ACTB, and CASC3 can be considered as stable reference genes, and B2M, RPII, UBC and GAPDH would not be appropriate. Although the rRNA-18S stability measure seems to be within the range of acceptance, its use is not recommended because its synthesis regulation is not representative of mRNA levels. Conclusion Based on geNorm algorithm, we propose the use of three genes SF3A1, EEF1A2 and HMBS as references for normalization of real-time RTqPCR in muscle expression studies.

  6. Identification of Reference Genes for RT-qPCR Data Normalization in Cannabis sativa Stem Tissues

    Directory of Open Access Journals (Sweden)

    Lauralie Mangeot-Peter

    2016-09-01

    Full Text Available Gene expression profiling via quantitative real-time PCR is a robust technique widely used in the life sciences to compare gene expression patterns in, e.g., different tissues, growth conditions, or after specific treatments. In the field of plant science, real-time PCR is the gold standard to study the dynamics of gene expression and is used to validate the results generated with high throughput techniques, e.g., RNA-Seq. An accurate relative quantification of gene expression relies on the identification of appropriate reference genes, that need to be determined for each experimental set-up used and plant tissue studied. Here, we identify suitable reference genes for expression profiling in stems of textile hemp (Cannabis sativa L., whose tissues (isolated bast fibres and core are characterized by remarkable differences in cell wall composition. We additionally validate the reference genes by analysing the expression of putative candidates involved in the non-oxidative phase of the pentose phosphate pathway and in the first step of the shikimate pathway. The goal is to describe the possible regulation pattern of some genes involved in the provision of the precursors needed for lignin biosynthesis in the different hemp stem tissues. The results here shown are useful to design future studies focused on gene expression analyses in hemp.

  7. Identification of Reference Genes for RT-qPCR Data Normalization in Cannabis sativa Stem Tissues.

    Science.gov (United States)

    Mangeot-Peter, Lauralie; Legay, Sylvain; Hausman, Jean-Francois; Esposito, Sergio; Guerriero, Gea

    2016-09-15

    Gene expression profiling via quantitative real-time PCR is a robust technique widely used in the life sciences to compare gene expression patterns in, e.g., different tissues, growth conditions, or after specific treatments. In the field of plant science, real-time PCR is the gold standard to study the dynamics of gene expression and is used to validate the results generated with high throughput techniques, e.g., RNA-Seq. An accurate relative quantification of gene expression relies on the identification of appropriate reference genes, that need to be determined for each experimental set-up used and plant tissue studied. Here, we identify suitable reference genes for expression profiling in stems of textile hemp (Cannabis sativa L.), whose tissues (isolated bast fibres and core) are characterized by remarkable differences in cell wall composition. We additionally validate the reference genes by analysing the expression of putative candidates involved in the non-oxidative phase of the pentose phosphate pathway and in the first step of the shikimate pathway. The goal is to describe the possible regulation pattern of some genes involved in the provision of the precursors needed for lignin biosynthesis in the different hemp stem tissues. The results here shown are useful to design future studies focused on gene expression analyses in hemp.

  8. Stem cell signaling. An integral program for tissue renewal and regeneration : Wnt signaling and stem cell control

    NARCIS (Netherlands)

    Clevers, Hans; Loh, Kyle M; Nusse, Roel

    2014-01-01

    Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified,

  9. Tissue artifact removal from respiratory signals based on empirical mode decomposition.

    Science.gov (United States)

    Liu, Shaopeng; Gao, Robert X; John, Dinesh; Staudenmayer, John; Freedson, Patty

    2013-05-01

    On-line measurement of respiration plays an important role in monitoring human physical activities. Such measurement commonly employs sensing belts secured around the rib cage and abdomen of the test object. Affected by the movement of body tissues, respiratory signals typically have a low signal-to-noise ratio. Removing tissue artifacts therefore is critical to ensuring effective respiration analysis. This paper presents a signal decomposition technique for tissue artifact removal from respiratory signals, based on the empirical mode decomposition (EMD). An algorithm based on the mutual information and power criteria was devised to automatically select appropriate intrinsic mode functions for tissue artifact removal and respiratory signal reconstruction. Performance of the EMD-algorithm was evaluated through simulations and real-life experiments (N = 105). Comparison with low-pass filtering that has been conventionally applied confirmed the effectiveness of the technique in tissue artifacts removal.

  10. Validation of putative reference genes for normalization of Q-RT-PCR data from paraffin-embedded lymphoid tissue

    DEFF Research Database (Denmark)

    Green, Tina Marie; de Stricker, Karin; Møller, Michael Boe

    2009-01-01

    Normalization of quantitative reverse transcription-PCR (Q-RT-PCR) data to appropriate tissue-specific reference genes is an essential part of interpreting the results. This study aimed to determine the most appropriate reference genes for normalizing gene expressions in lymphatic tissue...... was 0.93 (Pnormalization with the appropriate reference genes. Thus, we show that formalin-fixed, paraffin-embedded lymphoid samples are suitable for Q-RT-PCR when using thoroughly validated reference genes....

  11. Reference-tracking feedforward control design for linear dynamical systems through signal decomposition

    NARCIS (Netherlands)

    Kasemsinsup, Y.; Romagnoli, R.; Heertjes, M.F.; Weiland, S.; Butler, H.

    2017-01-01

    In this work, we study a novel approach towards the reference-tracking feedforward control design for linear dynamical systems. By utilizing the superposition property and exploiting signal decomposition together with a quadratic optimization process, we obtain a feedforward design procedure for

  12. Joint probability discrimination between stationary tissue and blood velocity signals

    DEFF Research Database (Denmark)

    Schlaikjer, Malene; Jensen, Jørgen Arendt

    2001-01-01

    before and after echo-canceling, and (b) the amplitude variations between samples in consecutive RF-signals before and after echo-canceling. The statistical discriminator was obtained by computing the probability density functions (PDFs) for each feature through histogram analysis of data....... This study presents a new statistical discriminator. Investigation of the RF-signals reveals that features can be derived that distinguish the segments of the signal, which do an do not carry information on the blood flow. In this study 4 features, have been determined: (a) the energy content in the segments....... The discrimination is performed by determining the joint probability of the features for the segment under investigation and choosing the segment type that is most likely. The method was tested on simulated data resembling RF-signals from the carotid artery....

  13. An image-based skeletal tissue model for the ICRP reference newborn

    Energy Technology Data Exchange (ETDEWEB)

    Pafundi, Deanna; Lee, Choonsik; Bolch, Wesley [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, FL (United States); Watchman, Christopher; Bourke, Vincent [Department of Radiation Oncology, University of Arizona, Tucson, AZ (United States); Aris, John [Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (United States); Shagina, Natalia [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation); Harrison, John; Fell, Tim [Radiation Protection Division, Health Protection Agency, Chilton (United Kingdom)], E-mail: wbolch@ufl.edu

    2009-07-21

    Hybrid phantoms represent a third generation of computational models of human anatomy needed for dose assessment in both external and internal radiation exposures. Recently, we presented the first whole-body hybrid phantom of the ICRP reference newborn with a skeleton constructed from both non-uniform rational B-spline and polygon-mesh surfaces (Lee et al 2007 Phys. Med. Biol. 52 3309-33). The skeleton in that model included regions of cartilage and fibrous connective tissue, with the remainder given as a homogenous mixture of cortical and trabecular bone, active marrow and miscellaneous skeletal tissues. In the present study, we present a comprehensive skeletal tissue model of the ICRP reference newborn to permit a heterogeneous representation of the skeleton in that hybrid phantom set-both male and female-that explicitly includes a delineation of cortical bone so that marrow shielding effects are correctly modeled for low-energy photons incident upon the newborn skeleton. Data sources for the tissue model were threefold. First, skeletal site-dependent volumes of homogeneous bone were obtained from whole-cadaver CT image analyses. Second, selected newborn bone specimens were acquired at autopsy and subjected to micro-CT image analysis to derive model parameters of the marrow cavity and bone trabecular 3D microarchitecture. Third, data given in ICRP Publications 70 and 89 were selected to match reference values on total skeletal tissue mass. Active marrow distributions were found to be in reasonable agreement with those given previously by the ICRP. However, significant differences were seen in total skeletal and site-specific masses of trabecular and cortical bone between the current and ICRP newborn skeletal tissue models. The latter utilizes an age-independent ratio of 80%/20% cortical and trabecular bone for the reference newborn. In the current study, a ratio closer to 40%/60% is used based upon newborn CT and micro-CT skeletal image analyses. These changes in

  14. Use of intrinsic fluorescent signals for characterizing tissue metabolic states in health and disease

    Science.gov (United States)

    Chance, Britton

    1996-04-01

    The large content of mitochondria in metabolizing cells, coupled with intrinsic NADH and flavoprotein signals makes these signals ideal for characterizing tissue metabolic states in health and disease. The first few millimeters of tissue are reached by the fluorescence excitation in the exposed surfaces of the cervix, bladder, rectum and esophagus, etc. Thus, extensive use has been made of fluorescent signals by a large number of investigators for tumor diagnosis from an empirical standpoint where the fluorescent signals are generally diminished in precancerous and cancerous tissue. This article reviews the biochemical basis for the fluorescent signals and points to a 'gold standard' for fluorescent signal examination involving freeze trapping and low temperature two- or three-dimensional high resolution fluorescence spectroscopy.

  15. Noncanonical Wnt signaling promotes obesity-induced adipose tissue inflammation and metabolic dysfunction independent of adipose tissue expansion.

    Science.gov (United States)

    Fuster, José J; Zuriaga, María A; Ngo, Doan Thi-Minh; Farb, Melissa G; Aprahamian, Tamar; Yamaguchi, Terry P; Gokce, Noyan; Walsh, Kenneth

    2015-04-01

    Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose tissue expansion. However, no genetic evidence supports a role for endogenous Wnt proteins in adipose tissue dysfunction, and the role of noncanonical Wnt signaling remains largely unexplored. Here we provide evidence from human, mouse, and cell culture studies showing that Wnt5a-mediated, noncanonical Wnt signaling contributes to obesity-associated metabolic dysfunction by increasing adipose tissue inflammation. Wnt5a expression is significantly upregulated in human visceral fat compared with subcutaneous fat in obese individuals. In obese mice, Wnt5a ablation ameliorates insulin resistance, in parallel with reductions in adipose tissue inflammation. Conversely, Wnt5a overexpression in myeloid cells augments adipose tissue inflammation and leads to greater impairments in glucose homeostasis. Wnt5a ablation or overexpression did not affect fat mass or adipocyte size. Mechanistically, Wnt5a promotes the expression of proinflammatory cytokines by macrophages in a Jun NH2-terminal kinase-dependent manner, leading to defective insulin signaling in adipocytes. Exogenous interleukin-6 administration restores insulin resistance in obese Wnt5a-deficient mice, suggesting a central role for this cytokine in Wnt5a-mediated metabolic dysfunction. Taken together, these results demonstrate that noncanonical Wnt signaling contributes to obesity-induced insulin resistance independent of adipose tissue expansion. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  16. Strategies and applications for incorporating physical and chemical signal gradients in tissue engineering.

    Science.gov (United States)

    Singh, Milind; Berkland, Cory; Detamore, Michael S

    2008-12-01

    From embryonic development to wound repair, concentration gradients of bioactive signaling molecules guide tissue formation and regeneration. Moreover, gradients in cellular and extracellular architecture as well as in mechanical properties are readily apparent in native tissues. Perhaps tissue engineers can take a cue from nature in attempting to regenerate tissues by incorporating gradients into engineering design strategies. Indeed, gradient-based approaches are an emerging trend in tissue engineering, standing in contrast to traditional approaches of homogeneous delivery of cells and/or growth factors using isotropic scaffolds. Gradients in tissue engineering lie at the intersection of three major paradigms in the field-biomimetic, interfacial, and functional tissue engineering-by combining physical (via biomaterial design) and chemical (with growth/differentiation factors and cell adhesion molecules) signal delivery to achieve a continuous transition in both structure and function. This review consolidates several key methodologies to generate gradients, some of which have never been employed in a tissue engineering application, and discusses strategies for incorporating these methods into tissue engineering and implant design. A key finding of this review was that two-dimensional physicochemical gradient substrates, which serve as excellent high-throughput screening tools for optimizing desired biomaterial properties, can be enhanced in the future by transitioning from two dimensions to three dimensions, which would enable studies of cell-protein-biomaterial interactions in a more native tissue-like environment. In addition, biomimetic tissue regeneration via combined delivery of graded physical and chemical signals appears to be a promising strategy for the regeneration of heterogeneous tissues and tissue interfaces. In the future, in vivo applications will shed more light on the performance of gradient-based mechanical integrity and signal delivery

  17. Added soft tissue contrast using signal attenuation and the fractal dimension for optical coherence tomography images of porcine arterial tissue

    International Nuclear Information System (INIS)

    Flueraru, C; Mao, Y; Chang, S; Popescu, D P; Sowa, M G

    2010-01-01

    Optical coherence tomography (OCT) images of left-descending coronary tissues harvested from three porcine specimens were acquired with a home-build swept-source OCT setup. Despite the fact that OCT is capable of acquiring high resolution circumferential images of vessels, many distinct histological features of a vessel have comparable optical properties leading to poor contrast in OCT images. Two classification methods were tested in this report for the purpose of enhancing contrast between soft-tissue components of porcine coronary vessels. One method involved analyzing the attenuation of the OCT signal as a function of light penetration into the tissue. We demonstrated that by analyzing the signal attenuation in this manner we were able to differentiate two media sub-layers with different orientations of the smooth muscle cells. The other classification method used in our study was fractal analysis. Fractal analysis was implemented in a box-counting (fractal dimension) image-processing code and was used as a tool to differentiate and quantify variations in tissue texture at various locations in the OCT images. The calculated average fractal dimensions had different values in distinct regions of interest (ROI) within the imaged coronary samples. When compared to the results obtained by using the attenuation of the OCT signal, the method of fractal analysis demonstrated better classification potential for distinguishing amongst the tissue ROI.

  18. Reference tissue modeling with parameter coupling: application to a study of SERT binding in HIV

    Energy Technology Data Exchange (ETDEWEB)

    Endres, Christopher J; Pomper, Martin G [Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD 21231 (United States); Hammoud, Dima A, E-mail: endres@jhmi.edu [Radiology and Imaging Sciences, National Institutes of Health/Clinical Center, Bethesda, MD (United States)

    2011-04-21

    When applicable, it is generally preferred to evaluate positron emission tomography (PET) studies using a reference tissue-based approach as that avoids the need for invasive arterial blood sampling. However, most reference tissue methods have been shown to have a bias that is dependent on the level of tracer binding, and the variability of parameter estimates may be substantially affected by noise level. In a study of serotonin transporter (SERT) binding in HIV dementia, it was determined that applying parameter coupling to the simplified reference tissue model (SRTM) reduced the variability of parameter estimates and yielded the strongest between-group significant differences in SERT binding. The use of parameter coupling makes the application of SRTM more consistent with conventional blood input models and reduces the total number of fitted parameters, thus should yield more robust parameter estimates. Here, we provide a detailed evaluation of the application of parameter constraint and parameter coupling to [{sup 11}C]DASB PET studies. Five quantitative methods, including three methods that constrain the reference tissue clearance (k{sup r}{sub 2}) to a common value across regions were applied to the clinical and simulated data to compare measurement of the tracer binding potential (BP{sub ND}). Compared with standard SRTM, either coupling of k{sup r}{sub 2} across regions or constraining k{sup r}{sub 2} to a first-pass estimate improved the sensitivity of SRTM to measuring a significant difference in BP{sub ND} between patients and controls. Parameter coupling was particularly effective in reducing the variance of parameter estimates, which was less than 50% of the variance obtained with standard SRTM. A linear approach was also improved when constraining k{sup r}{sub 2} to a first-pass estimate, although the SRTM-based methods yielded stronger significant differences when applied to the clinical study. This work shows that parameter coupling reduces the

  19. Method for increasing nuclear magnetic resonance signals in living biological tissue

    International Nuclear Information System (INIS)

    Krongrad, A.

    1995-01-01

    A method of enhancing a magnetic resonance comprising the steps of administering a quantity of a selected magnetic isotope to a living biological tissue at a concentration greater than the naturally occurring concentration of such isotope and detecting magnetic resonance signal from the administered magnetic isotope in the living biological tissue. (author)

  20. Facial soft tissue thicknesses: Noise, signal, and P.

    Science.gov (United States)

    Stephan, Carl N; Munn, Lachlan; Caple, Jodi

    2015-12-01

    Facial soft tissue thicknesses (FSTTs) hold an important role in craniofacial identification, forming the underlying quantitative basis of craniofacial superimposition and facial approximation methods. It is, therefore, important that patterns in FSTTs be correctly described and interpreted. In prior FSTT literature, small statistically significant differences have almost universally been overemphasized and misinterpreted to reflect sex and ancestry effects when they instead largely encode nuisance statistical noise. Here we examine FSTT data and give an overview of why P-values do not mean everything. Scientific inference, not mechanical evaluation of P, should be awarded higher priority and should form the basis of FSTT analysis. This hinges upon tempered consideration of many factors in addition to P, e.g., study design, sampling, measurement errors, repeatability, reproducibility, and effect size. While there are multiple lessons to be had, the underlying message is foundational: know enough statistics to avoid misinterpreting background noise for real biological effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Connective Tissue Disorders and Cardiovascular Complications: The indomitable role of Transforming Growth Factor-beta signaling

    Science.gov (United States)

    Wheeler, Jason B.; Ikonomidis, John S.; Jones, Jeffrey A.

    2015-01-01

    Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-β signaling pathway, heritable connective tissue syndromes related to TGF-β receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system. PMID:24443024

  2. Studying the distribution of deep Raman spectroscopy signals using liquid tissue phantoms with varying optical properties.

    Science.gov (United States)

    Vardaki, Martha Z; Gardner, Benjamin; Stone, Nicholas; Matousek, Pavel

    2015-08-07

    In this study we employed large volume liquid tissue phantoms, consisting of a scattering agent (Intralipid), an absorption agent (Indian ink) and a synthesized calcification powder (calcium hydroxyapatite (HAP)) similar to that found in cancerous tissues (e.g. breast and prostate), to simulate human tissues. We studied experimentally the magnitude and origin of Raman signals in a transmission Raman geometry as a function of optical properties of the medium and the location of calcifications within the phantom. The goal was to inform the development of future noninvasive cancer screening applications in vivo. The results provide insight into light propagation and Raman scattering distribution in deep Raman measurements, exploring also the effect of the variation of relative absorbance of laser and Raman photons within the phantoms. Most notably when modeling breast and prostate tissues it follows that maximum signals is obtained from the front and back faces of the tissue with the central region contributing less to the measured spectrum.

  3. The Somatic Reproductive Tissues of C. elegans Promote Longevity through Steroid Hormone Signaling

    Science.gov (United States)

    Yamawaki, Tracy M.; Berman, Jennifer R.; Suchanek-Kavipurapu, Monika; McCormick, Mark; Gaglia, Marta Maria; Lee, Seung-Jae; Kenyon, Cynthia

    2010-01-01

    In Caenorhabditis elegans and Drosophila melanogaster, removing the germline precursor cells increases lifespan. In worms, and possibly also in flies, this lifespan extension requires the presence of somatic reproductive tissues. How the somatic gonad signals other tissues to increase lifespan is not known. The lifespan increase triggered by loss of the germ cells is known to require sterol hormone signaling, as reducing the activity of the nuclear hormone receptor DAF-12, or genes required for synthesis of the DAF-12 ligand dafachronic acid, prevents germline loss from extending lifespan. In addition to sterol signaling, the FOXO transcription factor DAF-16 is required to extend lifespan in animals that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little or no effect on the expression of at least some DAF-16/FOXO target genes. In this study, we show that the DAF-12-sterol signaling pathway has a second function to activate a distinct set of genes and extend lifespan in response to the somatic reproductive tissues. When germline-deficient animals lacking somatic reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR-dependent target genes is restored and their lifespan is increased. Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12. PMID:20824162

  4. The somatic reproductive tissues of C. elegans promote longevity through steroid hormone signaling.

    Directory of Open Access Journals (Sweden)

    Tracy M Yamawaki

    2010-08-01

    Full Text Available In Caenorhabditis elegans and Drosophila melanogaster, removing the germline precursor cells increases lifespan. In worms, and possibly also in flies, this lifespan extension requires the presence of somatic reproductive tissues. How the somatic gonad signals other tissues to increase lifespan is not known. The lifespan increase triggered by loss of the germ cells is known to require sterol hormone signaling, as reducing the activity of the nuclear hormone receptor DAF-12, or genes required for synthesis of the DAF-12 ligand dafachronic acid, prevents germline loss from extending lifespan. In addition to sterol signaling, the FOXO transcription factor DAF-16 is required to extend lifespan in animals that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little or no effect on the expression of at least some DAF-16/FOXO target genes. In this study, we show that the DAF-12-sterol signaling pathway has a second function to activate a distinct set of genes and extend lifespan in response to the somatic reproductive tissues. When germline-deficient animals lacking somatic reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR-dependent target genes is restored and their lifespan is increased. Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12.

  5. Primary cilia and coordination of signaling pathways in heart development and tissue Homeostasis

    DEFF Research Database (Denmark)

    Clement, Christian Alexandro

    of primary cilia in coordinating Hh signaling in human pancreatic development and postnatal tissue homeostasis. In cultures of human pancreatic duct adenocarcinoma cell lines PANC-1 and CFPAC-1, Ptc in addition to Gli2 and Smo localize to primary cilia. These findings are consistent with the idea...... that the primary cilium continues to coordinate Hh signaling in cells derived from the mature pancreas. The fact that the Hh signaling pathway is active in the CFPAC-1 and PANC-1 cell lines without Hh stimulation suggests that ciliary Hh signaling plays a potential role in tumorigenesis. In conclusion, this thesis...

  6. Development of reference material for proficiency tests: arsenic in fish tissue

    International Nuclear Information System (INIS)

    Santana, Luciana Vieira de; Sarkis, Jorge E.S.; Ulrich, Joao C.; Hortellani, Marcos Antonio

    2013-01-01

    Proficiency tests (PT) are extensively used to evaluate the analytical competence of laboratories, and are also used as a part of accreditation processes. For this reason are important tool for quality control of laboratories including laboratories that act directly with food exporting companies. In Brazil there are no providers of proficiency testing for toxic metals, such as arsenic in fish tissue. This study presents a protocol to produce reference material to be used in proficiency test for arsenic in fish tissue following the recommendations of the ISO Guide 35. The preparation scheme consisted of: selecting of individuals, cleaning of scale and skin, trituration, homogenization, and spiking with arsenic at two levels of concentration. The mixture was then irradiated in a cyclotron Cyclone 30 Applications ion beam with cobalt 60 at 10.00 ± 1.05 KGy, before being packed into sachets. To verify the efficacy of the irradiation procedure, 26 (randomly selected) irradiated sachets and 26 non-irradiated sachets were assessed for homogeneity and stability. The results indicate that irradiation with cobalt 60 is crucial for ensuring the preservation of the integrity of the material, providing stable material at room temperature for 2 months. The samples can therefore be transported at room temperature. (author)

  7. Development of reference material for proficiency tests: arsenic in fish tissue

    Energy Technology Data Exchange (ETDEWEB)

    Santana, Luciana Vieira de; Sarkis, Jorge E.S.; Ulrich, Joao C.; Hortellani, Marcos Antonio, E-mail: santana-luciana@ig.com.br, E-mail: jesarkis@ipen.br, E-mail: jculrich@ipen.br, E-mail: mahortel@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Proficiency tests (PT) are extensively used to evaluate the analytical competence of laboratories, and are also used as a part of accreditation processes. For this reason are important tool for quality control of laboratories including laboratories that act directly with food exporting companies. In Brazil there are no providers of proficiency testing for toxic metals, such as arsenic in fish tissue. This study presents a protocol to produce reference material to be used in proficiency test for arsenic in fish tissue following the recommendations of the ISO Guide 35. The preparation scheme consisted of: selecting of individuals, cleaning of scale and skin, trituration, homogenization, and spiking with arsenic at two levels of concentration. The mixture was then irradiated in a cyclotron Cyclone 30 Applications ion beam with cobalt 60 at 10.00 ± 1.05 KGy, before being packed into sachets. To verify the efficacy of the irradiation procedure, 26 (randomly selected) irradiated sachets and 26 non-irradiated sachets were assessed for homogeneity and stability. The results indicate that irradiation with cobalt 60 is crucial for ensuring the preservation of the integrity of the material, providing stable material at room temperature for 2 months. The samples can therefore be transported at room temperature. (author)

  8. Temporal analysis of reflected optical signals for short pulse laser interaction with nonhomogeneous tissue phantoms

    International Nuclear Information System (INIS)

    Trivedi, Ashish; Basu, Soumyadipta; Mitra, Kunal

    2005-01-01

    The use of short pulse laser for minimally invasive detection scheme has become an indispensable tool in the technological arsenal of modern medicine and biomedical engineering. In this work, a time-resolved technique has been used to detect tumors/inhomogeneities in tissues by measuring transmitted and reflected scattered temporal optical signals when a short pulse laser source is incident on tissue phantoms. A parametric study involving different scattering and absorption coefficients of tissue phantoms and inhomogeneities, size of inhomogeneity as well as the detector position is performed. The experimental measurements are validated with a numerical solution of the transient radiative transport equation obtained by using discrete ordinates method. Thus, both simultaneous experimental and numerical studies are critical for predicting the optical properties of tissues and inhomogeneities from temporal scattered optical signal measurements

  9. Quantitative evaluation of deep and shallow tissue layers' contribution to fNIRS signal using multi-distance optodes and independent component analysis.

    Science.gov (United States)

    Funane, Tsukasa; Atsumori, Hirokazu; Katura, Takusige; Obata, Akiko N; Sato, Hiroki; Tanikawa, Yukari; Okada, Eiji; Kiguchi, Masashi

    2014-01-15

    To quantify the effect of absorption changes in the deep tissue (cerebral) and shallow tissue (scalp, skin) layers on functional near-infrared spectroscopy (fNIRS) signals, a method using multi-distance (MD) optodes and independent component analysis (ICA), referred to as the MD-ICA method, is proposed. In previous studies, when the signal from the shallow tissue layer (shallow signal) needs to be eliminated, it was often assumed that the shallow signal had no correlation with the signal from the deep tissue layer (deep signal). In this study, no relationship between the waveforms of deep and shallow signals is assumed, and instead, it is assumed that both signals are linear combinations of multiple signal sources, which allows the inclusion of a "shared component" (such as systemic signals) that is contained in both layers. The method also assumes that the partial optical path length of the shallow layer does not change, whereas that of the deep layer linearly increases along with the increase of the source-detector (S-D) distance. Deep- and shallow-layer contribution ratios of each independent component (IC) are calculated using the dependence of the weight of each IC on the S-D distance. Reconstruction of deep- and shallow-layer signals are performed by the sum of ICs weighted by the deep and shallow contribution ratio. Experimental validation of the principle of this technique was conducted using a dynamic phantom with two absorbing layers. Results showed that our method is effective for evaluating deep-layer contributions even if there are high correlations between deep and shallow signals. Next, we applied the method to fNIRS signals obtained on a human head with 5-, 15-, and 30-mm S-D distances during a verbal fluency task, a verbal working memory task (prefrontal area), a finger tapping task (motor area), and a tetrametric visual checker-board task (occipital area) and then estimated the deep-layer contribution ratio. To evaluate the signal separation

  10. A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference

    International Nuclear Information System (INIS)

    Namba, Hiroki; Nakagawa, Keiichi; Iyo, Masaomi; Fukushi, Kiyoshi; Irie, Toshiaki

    1994-01-01

    A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain-reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading. (orig.)

  11. Insulin signaling in various equine tissues under basal conditions and acute stimulation by intravenously injected insulin.

    Science.gov (United States)

    Warnken, Tobias; Brehm, Ralph; Feige, Karsten; Huber, Korinna

    2017-10-01

    The aim of the study was to analyze key proteins of the equine insulin signaling cascade and their extent of phosphorylation in biopsies from muscle tissue (MT), liver tissue (LT), and nuchal AT, subcutaneous AT, and retroperitoneal adipose tissues. This was investigated under unstimulated (B1) and intravenously insulin stimulated (B2) conditions, which were achieved by injection of insulin (0.1 IU/kg bodyweight) and glucose (150 mg/kg bodyweight). Twelve warmblood horses aged 15 ± 6.8 yr (yr), weighing 559 ± 79 kg, and with a mean body condition score of 4.7 ± 1.5 were included in the study. Key proteins of the insulin signaling cascade were semiquantitatively determined using Western blotting. Furthermore, modulation of the cascade was assessed. The basal expression of the proteins was only slightly influenced during the experimental period. Insulin induced a high extent of phosphorylation of insulin receptor in LT (P < 0.01) but not in MT. Protein kinase B and mechanistic target of rapamycin expressed a higher extent of phosphorylation in all tissues in B2 biopsies. Adenosine monophosphate protein kinase, as a component related to insulin signaling, expressed enhanced phosphorylation in MT (P < 0.05) and adipose tissues (nuchal AT P < 0.05; SCAT P < 0.01; retroperitoneal adipose tissue P < 0.05), but not in LT at B2. Tissue-specific variations in the acute response of insulin signaling to intravenously injected insulin were observed. In conclusion, insulin sensitivity in healthy horses is based on a complex concerted action of different tissues by their variations in the molecular response to insulin. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Ischiofemoral space on MRI in an asymptomatic population: Normative width measurements and soft tissue signal variations

    International Nuclear Information System (INIS)

    Maras Oezdemir, Zeynep; Goermeli, Cemile Ayse; Sagir Kahraman, Ayseguel; Aydingoez, Uestuen

    2015-01-01

    To make normative width measurements of the ischiofemoral (IF) space in an asymptomatic population and to record soft tissue MRI signal variations within the IF space in order to determine whether such variations are associated with IF space dimensions. Normative width measurements of the IF space were prospectively made in 418 hips on 1.5 T MR images of 209 asymptomatic volunteers. Quantitative and qualitative assessments of the IF soft tissues including the quadratus femoris (QF) muscle were also made. The mean IF space width was 2.56 ± 0.75 cm (right, 2.60 ± 0.75 cm; left, 2.53 ± 0.75 cm). Soft tissue MRI signal abnormalities were present within the IF space in 19 (9.1 %) of 209 volunteers. Soft tissue abnormalities within the IF space included oedema (3/209, 1.4 %) of the QF and/or surrounding soft tissue, and only fatty infiltration (16/209, 7.7 %) of the QF. Bilateral IF spaces are asymmetrical in asymptomatic persons. There is ≥10 % of width difference between right and left IF spaces in approximately half of asymptomatic individuals. Fatty infiltration and oedema can be present at the IF space in a small portion of the asymptomatic population, who also have narrower IF spaces than those without soft tissue MRI signal abnormalities. (orig.)

  13. A survey of clearing techniques for 3D imaging of tissues with special reference to connective tissue.

    Science.gov (United States)

    Azaripour, Adriano; Lagerweij, Tonny; Scharfbillig, Christina; Jadczak, Anna Elisabeth; Willershausen, Brita; Van Noorden, Cornelis J F

    2016-08-01

    For 3-dimensional (3D) imaging of a tissue, 3 methodological steps are essential and their successful application depends on specific characteristics of the type of tissue. The steps are 1° clearing of the opaque tissue to render it transparent for microscopy, 2° fluorescence labeling of the tissues and 3° 3D imaging. In the past decades, new methodologies were introduced for the clearing steps with their specific advantages and disadvantages. Most clearing techniques have been applied to the central nervous system and other organs that contain relatively low amounts of connective tissue including extracellular matrix. However, tissues that contain large amounts of extracellular matrix such as dermis in skin or gingiva are difficult to clear. The present survey lists methodologies that are available for clearing of tissues for 3D imaging. We report here that the BABB method using a mixture of benzyl alcohol and benzyl benzoate and iDISCO using dibenzylether (DBE) are the most successful methods for clearing connective tissue-rich gingiva and dermis of skin for 3D histochemistry and imaging of fluorescence using light-sheet microscopy. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  14. Selection of reference genes for tissue/organ samples on day 3 fifth-instar larvae in silkworm, Bombyx mori.

    Science.gov (United States)

    Wang, Genhong; Chen, Yanfei; Zhang, Xiaoying; Bai, Bingchuan; Yan, Hao; Qin, Daoyuan; Xia, Qingyou

    2018-06-01

    The silkworm, Bombyx mori, is one of the world's most economically important insect. Surveying variations in gene expression among multiple tissue/organ samples will provide clues for gene function assignments and will be helpful for identifying genes related to economic traits or specific cellular processes. To ensure their accuracy, commonly used gene expression quantification methods require a set of stable reference genes for data normalization. In this study, 24 candidate reference genes were assessed in 10 tissue/organ samples of day 3 fifth-instar B. mori larvae using geNorm and NormFinder. The results revealed that, using the combination of the expression of BGIBMGA003186 and BGIBMGA008209 was the optimum choice for normalizing the expression data of the B. mori tissue/organ samples. The most stable gene, BGIBMGA003186, is recommended if just one reference gene is used. Moreover, the commonly used reference gene encoding cytoplasmic actin was the least appropriate reference gene of the samples investigated. The reliability of the selected reference genes was further confirmed by evaluating the expression profiles of two cathepsin genes. Our results may be useful for future studies involving the quantification of relative gene expression levels of different tissue/organ samples in B. mori. © 2018 Wiley Periodicals, Inc.

  15. A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft Tissue Sarcomas

    Directory of Open Access Journals (Sweden)

    Michael D Deel

    2015-09-01

    Full Text Available The Hippo signaling pathway is an evolutionarily conserved developmental network vital for the regulation of organ size, tissue homeostasis, repair and regeneration, and cell fate. The Hippo pathway has also been shown to have tumor suppressor properties. Hippo transduction involves a series of kinases and scaffolding proteins that are intricately connected to proteins in developmental cascades and in the tissue microenvironment. This network governs the downstream Hippo transcriptional coactivators YAP and TAZ, which bind to and activate the output of TEADs, as well as other transcription factors responsible for cellular proliferation, self-renewal, differentiation, and survival. Surprisingly, there are few oncogenic mutations within the core components of the Hippo pathway. Instead, dysregulated Hippo signaling is a versatile accomplice to commonly mutated cancer pathways. For example, YAP and TAZ can be activated by oncogenic signaling from other pathways, or serve as coactivators for classical oncogenes. Emerging evidence suggests that Hippo signaling couples cell density and cytoskeletal structural changes to morphogenic signals, and conveys a mesenchymal phenotype. While much of Hippo biology has been described in epithelial cell systems, it is clear that dysregulated Hippo signaling also contributes to malignancies of mesenchymal origin. This review will summarize the known molecular alterations within the Hippo pathway in sarcomas, and highlight how several pharmacologic compounds have shown activity in modulating Hippo components, providing proof-of-principle that Hippo signaling may be harnessed for therapeutic application in sarcomas.

  16. Is the macromolecule signal tissue-specific in healthy human brain? A (1)H MRS study at 7 Tesla in the occipital lobe.

    Science.gov (United States)

    Schaller, Benoît; Xin, Lijing; Gruetter, Rolf

    2014-10-01

    The macromolecule signal plays a key role in the precision and the accuracy of the metabolite quantification in short-TE (1) H MR spectroscopy. Macromolecules have been reported at 1.5 Tesla (T) to depend on the cerebral studied region and to be age specific. As metabolite concentrations vary locally, information about the profile of the macromolecule signal in different tissues may be of crucial importance. The aim of this study was to investigate, at 7T for healthy subjects, the neurochemical profile differences provided by macromolecule signal measured in two different tissues in the occipital lobe, predominantly composed of white matter tissue or of grey matter tissue. White matter-rich macromolecule signal was relatively lower than the gray matter-rich macromolecule signal from 1.5 to 1.8 ppm and from 2.3 to 2.5 ppm with mean difference over these regions of 7% and 12% (relative to the reference peak at 0.9 ppm), respectively. The neurochemical profiles, when using either of the two macromolecule signals, were similar for 11 reliably quantified metabolites (CRLB occipital lobe at 7T in healthy human brain. Copyright © 2013 Wiley Periodicals, Inc.

  17. Suitability of cerebrospinal fluid as a signal-intensity reference on MRI: evaluation of signal-intensity variations in the lumbosacral dural sac

    International Nuclear Information System (INIS)

    Luoma, E.K.; Luukkonen, R.; Riihimaeki, H.A.; Raininko, R.; Manninen, H.I.; Nummi, P.J.

    1997-01-01

    The suitability of the cerebrospinal fluid (CSF) in the lumbosacral dural sac as an internal signal-intensity reference was studied on magnetic resonance imaging (MRI) of the lumbar spine using a surface coil and motion artefact suppression technique. A signal-intensity reference is needed when signal is compared between images, studies or subjects. Homogeneity of the CSF was estimated visually on T2-weighted images of 60 subjects at 1.5 T and of another 60 subjects at 0.1 T. Spines with a severely narrowed dural sac or marked scoliosis were excluded from the study to avoid partial volume effect. CSF was homogeneous in 82% and 73% of the examinations at 1.5 T and 0.1 T, respectively. The type and location of the local inhomogeneities did not relate to local narrowings of the dural sac. The signal intensity of CSF was measured in 108 examinations at 0.1 T after correcting the spatially-dependent signal-intensity nonuniformities with a phantom-based method. The signal-intensity difference between the CSF in the upper and lower lumbar dural sac was less than 10% in 73% of the examinations. The CSF in the lumbosacral dural sac can be a useful signal-intensity reference for estimation of the signal of the adjacent structures in patients without severe narrowing of the dural sac or marked scoliosis. It may contribute to assessing spinal disease processes. (orig.). With 1 fig., 3 tabs

  18. Fuz regulates craniofacial development through tissue specific responses to signaling factors.

    Directory of Open Access Journals (Sweden)

    Zichao Zhang

    Full Text Available The planar cell polarity effector gene Fuz regulates ciliogenesis and Fuz loss of function studies reveal an array of embryonic phenotypes. However, cilia defects can affect many signaling pathways and, in humans, cilia defects underlie several craniofacial anomalies. To address this, we analyzed the craniofacial phenotype and signaling responses of the Fuz(-/- mice. We demonstrate a unique role for Fuz in regulating both Hedgehog (Hh and Wnt/β-catenin signaling during craniofacial development. Fuz expression first appears in the dorsal tissues and later in ventral tissues and craniofacial regions during embryonic development coincident with cilia development. The Fuz(-/- mice exhibit severe craniofacial deformities including anophthalmia, agenesis of the tongue and incisors, a hypoplastic mandible, cleft palate, ossification/skeletal defects and hyperplastic malformed Meckel's cartilage. Hh signaling is down-regulated in the Fuz null mice, while canonical Wnt signaling is up-regulated revealing the antagonistic relationship of these two pathways. Meckel's cartilage is expanded in the Fuz(-/- mice due to increased cell proliferation associated with the up-regulation of Wnt canonical target genes and decreased non-canonical pathway genes. Interestingly, cilia development was decreased in the mandible mesenchyme of Fuz null mice, suggesting that cilia may antagonize Wnt signaling in this tissue. Furthermore, expression of Fuz decreased expression of Wnt pathway genes as well as a Wnt-dependent reporter. Finally, chromatin IP experiments demonstrate that β-catenin/TCF-binding directly regulates Fuz expression. These data demonstrate a new model for coordination of Hh and Wnt signaling and reveal a Fuz-dependent negative feedback loop controlling Wnt/β-catenin signaling.

  19. Fluid mechanics as a driver of tissue-scale mechanical signaling in organogenesis.

    Science.gov (United States)

    Gilbert, Rachel M; Morgan, Joshua T; Marcin, Elizabeth S; Gleghorn, Jason P

    2016-12-01

    Organogenesis is the process during development by which cells self-assemble into complex, multi-scale tissues. Whereas significant focus and research effort has demonstrated the importance of solid mechanics in organogenesis, less attention has been given to the fluid forces that provide mechanical cues over tissue length scales. Fluid motion and pressure is capable of creating spatial gradients of forces acting on cells, thus eliciting distinct and localized signaling patterns essential for proper organ formation. Understanding the multi-scale nature of the mechanics is critically important to decipher how mechanical signals sculpt developing organs. This review outlines various mechanisms by which tissues generate, regulate, and sense fluid forces and highlights the impact of these forces and mechanisms in case studies of normal and pathological development.

  20. Evaluation of candidate reference genes for normalization of quantitative RT-PCR in soybean tissues under various abiotic stress conditions.

    Directory of Open Access Journals (Sweden)

    Dung Tien Le

    Full Text Available Quantitative RT-PCR can be a very sensitive and powerful technique for measuring differential gene expression. Changes in gene expression induced by abiotic stresses are complex and multifaceted, which make determining stably expressed genes for data normalization difficult. To identify the most suitable reference genes for abiotic stress studies in soybean, 13 candidate genes collected from literature were evaluated for stability of expression under dehydration, high salinity, cold and ABA (abscisic acid treatments using delta CT and geNorm approaches. Validation of reference genes indicated that the best reference genes are tissue- and stress-dependent. With respect to dehydration treatment, the Fbox/ABC, Fbox/60s gene pairs were found to have the highest expression stability in the root and shoot tissues of soybean seedlings, respectively. Fbox and 60s genes are the most suitable reference genes across dehydrated root and shoot tissues. Under salt stress the ELF1b/IDE and Fbox/ELF1b are the most stably expressed gene pairs in roots and shoots, respectively, while 60s/Fbox is the best gene pair in both tissues. For studying cold stress in roots or shoots, IDE/60s and Fbox/Act27 are good reference gene pairs, respectively. With regard to gene expression analysis under ABA treatment in either roots, shoots or across these tissues, 60s/ELF1b, ELF1b/Fbox and 60s/ELF1b are the most suitable reference genes, respectively. The expression of ELF1b/60s, 60s/Fbox and 60s/Fbox genes was most stable in roots, shoots and both tissues, respectively, under various stresses studied. Among the genes tested, 60s was found to be the best reference gene in different tissues and under various stress conditions. The highly ranked reference genes identified from this study were proved to be capable of detecting subtle differences in expression rates that otherwise would be missed if a less stable reference gene was used.

  1. Heat stress differentially modifies ethylene biosynthesis and signaling in pea floral and fruit tissues.

    Science.gov (United States)

    Savada, Raghavendra P; Ozga, Jocelyn A; Jayasinghege, Charitha P A; Waduthanthri, Kosala D; Reinecke, Dennis M

    2017-10-01

    Ethylene biosynthesis is regulated in reproductive tissues in response to heat stress in a manner to optimize resource allocation to pollinated fruits with developing seeds. High temperatures during reproductive development are particularly detrimental to crop fruit/seed production. Ethylene plays vital roles in plant development and abiotic stress responses; however, little is known about ethylene's role in reproductive tissues during development under heat stress. We assessed ethylene biosynthesis and signaling regulation within the reproductive and associated tissues of pea during the developmental phase that sets the stage for fruit-set and seed development under normal and heat-stress conditions. The transcript abundance profiles of PsACS [encode enzymes that convert S-adenosyl-L-methionine to 1-aminocyclopropane-1-carboxylic acid (ACC)] and PsACO (encode enzymes that convert ACC to ethylene), and ethylene evolution were developmentally, environmentally, and tissue-specifically regulated in the floral/fruit/pedicel tissues of pea. Higher transcript abundance of PsACS and PsACO in the ovaries, and PsACO in the pedicels was correlated with higher ethylene evolution and ovary senescence and pedicel abscission in fruits that were not pollinated under control temperature conditions. Under heat-stress conditions, up-regulation of ethylene biosynthesis gene expression in pre-pollinated ovaries was also associated with higher ethylene evolution and lower retention of these fruits. Following successful pollination and ovule fertilization, heat-stress modified PsACS and PsACO transcript profiles in a manner that suppressed ovary ethylene evolution. The normal ethylene burst in the stigma/style and petals following pollination was also suppressed by heat-stress. Transcript abundance profiles of ethylene receptor and signaling-related genes acted as qualitative markers of tissue ethylene signaling events. These data support the hypothesis that ethylene biosynthesis is

  2. Wnt and BMP signaling crosstalk in regulating dental stem cells: Implications in dental tissue engineering

    Directory of Open Access Journals (Sweden)

    Fugui Zhang

    2016-12-01

    Full Text Available Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling. Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance, essential oral functions and the quality of life. Regenerative dentistry holds great promise in treating oral/dental disorders. The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells, along with the signaling mechanisms governing stem cell self-renewal and differentiation. In this review, we first summarize the biological characteristics of seven types of dental stem cells, including dental pulp stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, periodontal ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs, and MSCs from gingiva. We then focus on how these stem cells are regulated by bone morphogenetic protein (BMP and/or Wnt signaling by examining the interplays between these pathways. Lastly, we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways. We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications. Thus, we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.

  3. Validation of potential reference genes for qPCR in maize across abiotic stresses, hormone treatments, and tissue types.

    Directory of Open Access Journals (Sweden)

    Yueai Lin

    Full Text Available The reverse transcription quantitative polymerase chain reaction (RT-qPCR is a powerful and widely used technique for the measurement of gene expression. Reference genes, which serve as endogenous controls ensure that the results are accurate and reproducible, are vital for data normalization. To bolster the literature on reference gene selection in maize, ten candidate reference genes, including eight traditionally used internal control genes and two potential candidate genes from our microarray datasets, were evaluated for expression level in maize across abiotic stresses (cold, heat, salinity, and PEG, phytohormone treatments (abscisic acid, salicylic acid, jasmonic acid, ethylene, and gibberellins, and different tissue types. Three analytical software packages, geNorm, NormFinder, and Bestkeeper, were used to assess the stability of reference gene expression. The results revealed that elongation factor 1 alpha (EF1α, tubulin beta (β-TUB, cyclophilin (CYP, and eukaryotic initiation factor 4A (EIF4A were the most reliable reference genes for overall gene expression normalization in maize, while GRP (Glycine-rich RNA-binding protein, GLU1(beta-glucosidase, and UBQ9 (ubiquitin 9 were the least stable and most unsuitable genes. In addition, the suitability of EF1α, β-TUB, and their combination as reference genes was confirmed by validating the expression of WRKY50 in various samples. The current study indicates the appropriate reference genes for the urgent requirement of gene expression normalization in maize across certain abiotic stresses, hormones, and tissue types.

  4. SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods

    NARCIS (Netherlands)

    Schuitemaker, Alie; van Berckel, Bart N. M.; Kropholler, Marc A.; Veltman, Dick J.; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A.; Boellaard, Ronald

    2007-01-01

    (R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to

  5. Cell density signal protein suitable for treatment of connective tissue injuries and defects

    Science.gov (United States)

    Schwarz, Richard I.

    2002-08-13

    Identification, isolation and partial sequencing of a cell density protein produced by fibroblastic cells. The cell density signal protein comprising a 14 amino acid peptide or a fragment, variant, mutant or analog thereof, the deduced cDNA sequence from the 14 amino acid peptide, a recombinant protein, protein and peptide-specific antibodies, and the use of the peptide and peptide-specific antibodies as therapeutic agents for regulation of cell differentiation and proliferation. A method for treatment and repair of connective tissue and tendon injuries, collagen deficiency, and connective tissue defects.

  6. Nodal signals mediate interactions between the extra-embryonic and embryonic tissues in zebrafish

    OpenAIRE

    Xiang, Fan; Hagos, Engda G.; Xu, Bo; Sias, Christina; Kawakami, Koichi; Burdine, Rebecca D.; Dougan, Scott T.

    2007-01-01

    In many vertebrates, extra-embryonic tissues are important signaling centers that induce and pattern the germ layers. In teleosts, the mechanism by which the extra-embryonic yolk syncytial layer (YSL) patterns the embryo is not understood. Although the Nodal-related protein Squint is expressed in the YSL, its role in this tissue is not known. We generated a series of stable transgenic lines with GFP under the control of squint genomic sequences. In all species, nodal-related genes induce thei...

  7. Multi-geodetic characterization of the seasonal signal at the CERGA geodetic reference, France

    Science.gov (United States)

    Memin, A.; Viswanathan, V.; Fienga, A.; Santamaría-Gómez, A.; Boy, J. P.

    2016-12-01

    Crustal deformations due to surface-mass loading account for a significant part of the variability in geodetic time series. A perfect understanding of the loading signal observed by geodetic techniques should help in improving terrestrial reference frame (TRF) realizations. Yet, discrepancies between crustal motion estimates from models of surface-mass loading and observations are still too large so that no model is currently recommended by the IERS for reducing the data. We investigate the discrepancy observed in the seasonal variations of the CERGA station, South of France.We characterize the seasonal motions of the reference geodetic station CERGA from GNSS, SLR and LLR. We compare the station motion observed with GNSS and SLR and we estimate changes in the station-to-the-moon distance using an improved processing strategy. We investigate the consistency between these geodetic techniques and compare the observed station motion with that estimated using models of surface-mass change. In that regard, we compute atmospheric loading effects using surface pressure fields from ECMWF, assuming an ocean response according to the classical inverted barometer (IB) assumption, considered to be valid for periods typically exceeding a week. We also used general circulation ocean models (ECCO and GLORYS) forced by wind, heat and fresh water fluxes. The continental water storage is described using GLDAS/Noah and MERRA-land models.Using the surface-mass models, we estimate the amplitude of the seasonal vertical motion of the CERGA station ranging between 5 and 10 mm with a maximum reached in August, mostly due to hydrology. The horizontal seasonal motion of the station may reach up to 3 mm. Such a station motion should induce a change in the distance to the moon reaching up to 10 mm, large enough to be detected in LLR time series and compared to GNSS- and SLR-derived motion.

  8. Investigating electro-mechanical signals from collocated piezoelectric wafers for the reference-free damage diagnosis of a plate

    International Nuclear Information System (INIS)

    Kim, Eun Jin; Park, Hyun Woo; Kim, Min Koo; Sohn, Hoon

    2011-01-01

    The electro-mechanical (EM) signals from piezoelectric (PZT) wafers are investigated for reference-free damage diagnosis so that a notch in a plate can be detected without requiring direct comparison with a baseline EM signal. Two identical PZT wafers collocated on both surfaces of a plate are utilized for extracting the mode-converted Lamb wave signals created by a notch. As harmonic input voltage signals are exerted on the collocated PZT wafers, the corresponding mode-converted Lamb wave signals become steady-state in the presence of damage. Applying fast Fourier transform to these mode-converted Lamb wave signals followed by a proper normalization, the EM signals associated with the mode conversion can be obtained. The theoretical finding of this paper is validated through spectral element simulations of a cantilever beam with a notch. The effects of the size and the location of the notch on the mode-converted EM signals are investigated as well. Finally, the applicability of the decomposed EM signals to reference-free damage diagnosis is discussed

  9. Numerical prediction and measurement of optoacoustic signals generated in PVA-H tissue phantoms

    Science.gov (United States)

    Melchert, Oliver; Blumenröther, Elias; Wollweber, Merve; Roth, Bernhard

    2018-01-01

    We present numerical simulations of optoacoustic (OA) signals, complementing laboratory experiments on melanin doped polyvinyl alcohol hydrogel (PVA-H) tissue phantoms. We review the computational approach to model the underlying mechanisms, i.e. optical absorption of laser energy and acoustic propagation of mechanical stress, geared toward experiments that involve absorbing media with homogeneous acoustic properties. We apply the numerical procedure to predict signals observed in the acoustic near- and farfield in both, forward and backward detection mode, in PVA-H tissue phantoms (i.e. an elastic solid). Further, we report on verification tests of our research code based on OA experiments on dye solution (i.e. a liquid) detailed in the literature and benchmark our 3D procedure via limiting cases described in terms of effectively 1D theoretical approaches.

  10. Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization.

    Science.gov (United States)

    Dzamba, Bette J; Jakab, Karoly R; Marsden, Mungo; Schwartz, Martin A; DeSimone, Douglas W

    2009-03-01

    In this study we demonstrate that planar cell polarity signaling regulates morphogenesis in Xenopus embryos in part through the assembly of the fibronectin (FN) matrix. We outline a regulatory pathway that includes cadherin adhesion and signaling through Rac and Pak, culminating in actin reorganization, myosin contractility, and tissue tension, which, in turn, directs the correct spatiotemporal localization of FN into a fibrillar matrix. Increased mechanical tension promotes FN fibril assembly in the blastocoel roof (BCR), while reduced BCR tension inhibits matrix assembly. These data support a model for matrix assembly in tissues where cell-cell adhesions play an analogous role to the focal adhesions of cultured cells by transferring to integrins the tension required to direct FN fibril formation at cell surfaces.

  11. Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells

    OpenAIRE

    Falank, Carolyne; Fairfield, Heather; Reagan, Michaela R.

    2016-01-01

    In the year 2000, Hanahan and Weinberg (1) defined the six Hallmarks of Cancer as: self-sufficiency in growth signals, evasion of apoptosis, insensitivity to antigrowth mechanisms, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis. Eleven years later, two new Hallmarks were added to the list (avoiding immune destruction and reprograming energy metabolism) and two new tumor characteristics (tumor-promoting inflammation and genome instability and mutati...

  12. Certification of methylmercury content in two fresh-frozen reference materials: SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis)

    International Nuclear Information System (INIS)

    Davis, W.C.; Christopher, S.J.; Pugh, Rebecca S.; Donard, O.F.X.; Krupp, Eva A.; Point, David; Horvat, Milena; Gibicar, D.; Kljakovic-Gaspic, Z.; Porter, Barbara J.; Schantz, Michele M.

    2007-01-01

    This paper describes the development of two independent analytical methods for the extraction and quantification of methylmercury from marine biota. The procedures involve microwave extraction, followed by derivatization and either headspace solid-phase microextraction (SPME) with a polydimethylsiloxane (PDMS)-coated silica fiber or back-extraction into iso-octane. The identification and quantification of the extracted compounds is carried out by capillary gas chromatography/mass spectrometric (GC/MS) and inductively coupled plasma mass spectrometric (GC/ICP-MS) detection. Both methods were validated for the determination of methylmercury (MeHg) concentrations in a variety of biological standard reference materials (SRMs) including fresh-frozen tissue homogenates of SRM 1946 Lake Superior fish tissue and SRM 1974a organics in mussel tissue (Mytilus edulis) and then applied to the certification effort of SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis). While past certifications of methylmercury in tissue SRMs have been based on two independent methods from the National Institute of Standards and Technology (NIST) and participating laboratories, the methods described within provide improved protocols and will allow future certification efforts to be based on at least two independent analytical methods within NIST. (orig.)

  13. Certification of methylmercury content in two fresh-frozen reference materials: SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis)

    Energy Technology Data Exchange (ETDEWEB)

    Davis, W.C.; Christopher, S.J.; Pugh, Rebecca S. [National Institute of Standards and Technology (NIST), Hollings Marine Laboratory, Analytical Chemistry Division, Charleston, SC (United States); Donard, O.F.X.; Krupp, Eva A. [LCABIE/CNRS Helioparc Pau-Pyrenees, Pau (France); Point, David [National Institute of Standards and Technology (NIST), Hollings Marine Laboratory, Analytical Chemistry Division, Charleston, SC (United States); LCABIE/CNRS Helioparc Pau-Pyrenees, Pau (France); Horvat, Milena; Gibicar, D. [Jozef Stefan Institute, Ljubljana (Slovenia); Kljakovic-Gaspic, Z. [Jozef Stefan Institute, Ljubljana (Slovenia); Institute for Medical Research and Occupational Health, Zagreb (Croatia); Porter, Barbara J.; Schantz, Michele M. [National Institute of Standards and Technology (NIST), Analytical Chemistry Division, Gaithersburg, MD (United States)

    2007-04-15

    This paper describes the development of two independent analytical methods for the extraction and quantification of methylmercury from marine biota. The procedures involve microwave extraction, followed by derivatization and either headspace solid-phase microextraction (SPME) with a polydimethylsiloxane (PDMS)-coated silica fiber or back-extraction into iso-octane. The identification and quantification of the extracted compounds is carried out by capillary gas chromatography/mass spectrometric (GC/MS) and inductively coupled plasma mass spectrometric (GC/ICP-MS) detection. Both methods were validated for the determination of methylmercury (MeHg) concentrations in a variety of biological standard reference materials (SRMs) including fresh-frozen tissue homogenates of SRM 1946 Lake Superior fish tissue and SRM 1974a organics in mussel tissue (Mytilus edulis) and then applied to the certification effort of SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis). While past certifications of methylmercury in tissue SRMs have been based on two independent methods from the National Institute of Standards and Technology (NIST) and participating laboratories, the methods described within provide improved protocols and will allow future certification efforts to be based on at least two independent analytical methods within NIST. (orig.)

  14. A novel SNP analysis method to detect copy number alterations with an unbiased reference signal directly from tumor samples

    Directory of Open Access Journals (Sweden)

    LaFramboise William A

    2011-01-01

    Full Text Available Abstract Background Genomic instability in cancer leads to abnormal genome copy number alterations (CNA as a mechanism underlying tumorigenesis. Using microarrays and other technologies, tumor CNA are detected by comparing tumor sample CN to normal reference sample CN. While advances in microarray technology have improved detection of copy number alterations, the increase in the number of measured signals, noise from array probes, variations in signal-to-noise ratio across batches and disparity across laboratories leads to significant limitations for the accurate identification of CNA regions when comparing tumor and normal samples. Methods To address these limitations, we designed a novel "Virtual Normal" algorithm (VN, which allowed for construction of an unbiased reference signal directly from test samples within an experiment using any publicly available normal reference set as a baseline thus eliminating the need for an in-lab normal reference set. Results The algorithm was tested using an optimal, paired tumor/normal data set as well as previously uncharacterized pediatric malignant gliomas for which a normal reference set was not available. Using Affymetrix 250K Sty microarrays, we demonstrated improved signal-to-noise ratio and detected significant copy number alterations using the VN algorithm that were validated by independent PCR analysis of the target CNA regions. Conclusions We developed and validated an algorithm to provide a virtual normal reference signal directly from tumor samples and minimize noise in the derivation of the raw CN signal. The algorithm reduces the variability of assays performed across different reagent and array batches, methods of sample preservation, multiple personnel, and among different laboratories. This approach may be valuable when matched normal samples are unavailable or the paired normal specimens have been subjected to variations in methods of preservation.

  15. Climatic signals registered as Carbon isotopic values in Metasequoia leaf tissues: A statistical analysis

    Science.gov (United States)

    Yang, H.; Blais, B.; Perez, G.; Pagani, M.

    2006-12-01

    To examine climatic signals registered as carbon isotopic values in leaf tissues of C3 plants, we collected mature leaf tissues from sun and shade leaves of Metasequoia trees germinated from the 1947 batch of seeds from China and planted along a latitudinal gradient of the United States. Samples from 40 individual trees, along with fossilized material from the early Tertiary of the Canadian Arctic, were analyzed for C and concentration and isotopic values using EA-IRMS after the removal of free lipids. The generated datasets were then merged with climate data compiled from each tree site recorded as average values over the past thirty years (1971-2002, NOAA database). When the isotope data were cross plotted against each geographic and climatic indicator, Latitude, Mean Annual Temperature (MAT), Average Summer Mean Temperature (ASMT)(June-August), Mean Annual Precipitation (MAP), and Average Summer Mean Precipitation (ASMP) respectively correlation patterns were revealed. The best correlating trend was obtained between temperature parameters and C isotopic values, and this correlation is stronger in the northern leaf samples than the southern samples. We discovered a strong positive correlation between latitude and the offset of C isotopic values between shade and sun leaves. This investigation represents a comprehensive examination on climatic signals registered as C isotopic values on a single species that is marked by single genetic source. The results bear implications on paleoclimatic interpretations of C isotopic signals obtained from fossil plant tissues.

  16. Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation.

    Science.gov (United States)

    Manteiga, Sara; Choi, Kyungoh; Jayaraman, Arul; Lee, Kyongbum

    2013-01-01

    Adipose tissue (AT) depots actively regulate whole body energy homeostasis by orchestrating complex communications with other physiological systems as well as within the tissue. Adipocytes readily respond to hormonal and nutritional inputs to store excess nutrients as intracellular lipids or mobilize the stored fat for utilization. Co-ordinated regulation of metabolic pathways balancing uptake, esterification, and hydrolysis of lipids is accomplished through positive and negative feedback interactions of regulatory hubs comprising several pleiotropic protein kinases and nuclear receptors. Metabolic regulation in adipocytes encompasses biogenesis and remodeling of uniquely large lipid droplets (LDs). The regulatory hubs also function as energy and nutrient sensors, and integrate metabolic regulation with intercellular signaling. Over-nutrition causes hypertrophic expansion of adipocytes, which, through incompletely understood mechanisms, initiates a cascade of metabolic and signaling events leading to tissue remodeling and immune cell recruitment. Macrophage activation and polarization toward a pro-inflammatory phenotype drives a self-reinforcing cycle of pro-inflammatory signals in the AT, establishing an inflammatory state. Sustained inflammation accelerates lipolysis and elevates free fatty acids in circulation, which robustly correlates with development of obesity-related diseases. The adipose regulatory network coupling metabolism, growth, and signaling of multiple cell types is exceedingly complex. While components of the regulatory network have been individually studied in exquisite detail, systems approaches have rarely been utilized to comprehensively assess the relative engagements of the components. Thus, need and opportunity exist to develop quantitative models of metabolic and signaling networks to achieve a more complete understanding of AT biology in both health and disease. Copyright © 2013 Wiley Periodicals, Inc.

  17. A theoretical analysis of damage evolution in skeletal muscle tissue with reference to pressure ulcer development

    NARCIS (Netherlands)

    Breuls, R.G.M.; Bouten, C.V.C.; Oomens, C.W.J.; Bader, D.L.; Baaijens, F.P.T.

    2003-01-01

    Soft tissues are sensitive to prolonged compressive loading, eventually leading to tissue necrosis in the form of pressure ulcers [1]. Pressure ulcers can occur in situations where people are subjected to sustained mechanical loads, such as when bedridden, sitting in a wheelchair or from wearing

  18. CHARACTERIZATION AND AUTOMATIC COUNTING OF F.I.S.H. SIGNALS IN 3-D TISSUE IMAGES

    Directory of Open Access Journals (Sweden)

    Umesh PS Adiga

    2011-05-01

    Full Text Available The evaluation of malignancy-related features often helps to determine the prognoses for patients with carcinomas. One technique, which is becoming increasingly important for assessing such prognostic features is that of Fluorescence in situ Hybridization (FISH. By counting the number of FISH signals in a stack of 2- D images of a tumor (which together constitute the 3-D image volume, it is possible to determine whether there has been any loss or gain of the target DNA sequences and thereby evaluate the stage of the disease. However, visual counting of the FISH signals in this way is a tedious, fatiguing and time-consuming task. Therefore, we have developed an automated system for the quantitative evaluation of FISH signals. We present and discuss the implementation of an image processing module that segments, characterizes and counts the FISH signals in 3-D images of thick prostate tumor tissue specimens. Possible errors in the automatic counting of signals are listed and ways to circumvent these errors are described. We define a feature vector for a FISH signal and describe how we have used the weighted feature vector to segment specific signals from noise artifacts. In addition, we present a method, which allows overlapping FISH signals to be distinguished by fitting a local Gaussian model around the intensity profile and studying the feature vector of each model. Our complete image processing module overcomes the problems of manual counting of FISH signals in 3-D images of tumor specimens, thereby providing improved diagnostic and prognostic capability in qualitative diagnostic pathology.

  19. Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration.

    Science.gov (United States)

    Glaser, Talita; Cappellari, Angélica Regina; Pillat, Micheli Mainardi; Iser, Isabele Cristiana; Wink, Márcia Rosângela; Battastini, Ana Maria Oliveira; Ulrich, Henning

    2012-09-01

    Replacement of lost or dysfunctional tissues by stem cells has recently raised many investigations on therapeutic applications. Purinergic signaling has been shown to regulate proliferation, differentiation, cell death, and successful engraftment of stem cells originated from diverse origins. Adenosine triphosphate release occurs in a controlled way by exocytosis, transporters, and lysosomes or in large amounts from damaged cells, which is then subsequently degraded into adenosine. Paracrine and autocrine mechanisms induced by immune responses present critical factors for the success of stem cell therapy. While P1 receptors generally exert beneficial effects including anti-inflammatory activity, P2 receptor-mediated actions depend on the subtype of stimulated receptors and localization of tissue repair. Pro-inflammatory actions and excitatory tissue damages mainly result from P2X7 receptor activation, while other purinergic receptor subtypes participate in proliferation and differentiation, thereby providing adequate niches for stem cell engraftment and novel mechanisms for cell therapy and endogenous tissue repair. Therapeutic applications based on regulation of purinergic signaling are foreseen for kidney and heart muscle regeneration, Clara-like cell replacement for pulmonary and bronchial epithelial cells as well as for induction of neurogenesis in case of neurodegenerative diseases.

  20. E4orf1 induction in adipose tissue promotes insulin-independent signaling in the adipocyte.

    Science.gov (United States)

    Kusminski, Christine M; Gallardo-Montejano, Violeta I; Wang, Zhao V; Hegde, Vijay; Bickel, Perry E; Dhurandhar, Nikhil V; Scherer, Philipp E

    2015-10-01

    Type 2 diabetes remains a worldwide epidemic with major pathophysiological changes as a result of chronic insulin resistance. Insulin regulates numerous biochemical pathways related to carbohydrate and lipid metabolism. We have generated a novel mouse model that allows us to constitutively activate, in an inducible fashion, the distal branch of the insulin signaling transduction pathway specifically in adipocytes. Using the adenoviral 36 E4orf1 protein, we chronically stimulate locally the Ras-ERK-MAPK signaling pathway. At the whole body level, this leads to reduced body-weight gain under a high fat diet challenge. Despite overlapping glucose tolerance curves, there is a reduced requirement for insulin action under these conditions. The mice further exhibit reduced circulating adiponectin levels that ultimately lead to impaired lipid clearance, and inflamed and fibrotic white adipose tissues. Nevertheless, they are protected from diet-induced hepatic steatosis. As we observe constitutively elevated p-Akt levels in the adipocytes, even under conditions of low insulin levels, this pinpoints enhanced Ras-ERK-MAPK signaling in transgenic adipocytes as a potential alternative route to bypass proximal insulin signaling events. We conclude that E4orf1 expression in the adipocyte leads to enhanced baseline activation of the distal insulin signaling node, yet impaired insulin receptor stimulation in the presence of insulin, with important implications for the regulation of adiponectin secretion. The resulting systemic phenotype is complex, yet highlights the powerful nature of manipulating selective branches of the insulin signaling network within the adipocyte.

  1. Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1.

    Science.gov (United States)

    Galeone, Antonio; Han, Seung Yeop; Huang, Chengcheng; Hosomi, Akira; Suzuki, Tadashi; Jafar-Nejad, Hamed

    2017-08-04

    Mutations in the human N- glycanase 1 ( NGLY1 ) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N -glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N -glycanase enzyme.

  2. Biomechanical signals guiding stem cell cartilage engineering: from molecular adaption to tissue functionality

    Directory of Open Access Journals (Sweden)

    Y Zhang

    2016-01-01

    Full Text Available In vivo cartilage is in a state of constant mechanical stimulation. It is therefore reasonable to deduce that mechanical forces play an important role in cartilage formation. Mechanical forces, such as compression, tension, and shear force, have been widely applied for cartilage engineering; however, relatively few review papers have summarized the influence of biomechanical signals on stem cell-based neo-cartilage formation and cartilage engineering in both molecular adaption and tissue functionality. In this review, we will discuss recent progress related to the influences of substrate elasticity on stem cell chondrogenic differentiation and elucidate the potential underlying mechanisms. Aside from active sensing and responding to the extracellular environment, stem cells also could respond to various external mechanical forces, which also influence their chondrogenic capacity; this topic will be updated along with associated signaling pathways. We expect that these different regimens of biomechanical signals can be utilized to boost stem cell-based cartilage engineering and regeneration.

  3. Equilibrium Passive Sampling of POP in Lipid-Rich and Lean Fish Tissue: Quality Control Using Performance Reference Compounds.

    Science.gov (United States)

    Rusina, Tatsiana P; Carlsson, Pernilla; Vrana, Branislav; Smedes, Foppe

    2017-10-03

    Passive sampling is widely used to measure levels of contaminants in various environmental matrices, including fish tissue. Equilibrium passive sampling (EPS) of persistent organic pollutants (POP) in fish tissue has been hitherto limited to application in lipid-rich tissue. We tested several exposure methods to extend EPS applicability to lean tissue. Thin-film polydimethylsiloxane (PDMS) passive samplers were exposed statically to intact fillet and fish homogenate and dynamically by rolling with cut fillet cubes. The release of performance reference compounds (PRC) dosed to passive samplers prior to exposure was used to monitor the exchange process. The sampler-tissue exchange was isotropic, and PRC were shown to be good indicators of sampler-tissue equilibration status. The dynamic exposures demonstrated equilibrium attainment in less than 2 days for all three tested fish species, including lean fish containing 1% lipid. Lipid-based concentrations derived from EPS were in good agreement with lipid-normalized concentrations obtained using conventional solvent extraction. The developed in-tissue EPS method is robust and has potential for application in chemical monitoring of biota and bioaccumulation studies.

  4. On fibrinolytic phenomenon in the cancerous tissue of cervical carcinoma with special reference to irradiation changes

    International Nuclear Information System (INIS)

    Nakamura, Kazuyoshi

    1978-01-01

    In a study undertaken to investigate alterations of fibrinolytic enzymes in cancerous tissue of the cervix under radiotherapy, specimens were taken from malignant tissues of cervical cancer patients during irradiation therapy with Linac x-ray at 1000, 2000 and 3000 rads and were subsequently assayed for fibrinolytic enzyme activities using the fibrin plate method. No plasmin activity was demonstrable in the normal mucosa of the uterine cervix. Cancerous tissue of the uterine cervix also showed no demonstrable plasmin activity. The malignant tissue, as compared to the normal mucosa of the cervix, was found to have a lower activator activity, a higher proactivator activity and lower activities of both antiplasmin inhibitors. During radiotherapy for cervical cancer, plasmin activity was demonstrable in the cancerous tissue and in patients with malignant neoplasm, demonstrating that plasmin activity increased as the radiation dose was increased. A relationship seemed to exist between morphological changes and alterations in the fibrinolytic system of cancerous tissue of the cervix. From these findings it seems that the altered fibrinolytic enzyme system in cancerous tissue may have a close relationship with the growth and development of malignancy and may also have an important role in the occurrence of metastasis. There were some cases, in which an abnormal increase in activator activity occurred during irradiation therapy, leading to the death of the patients. This fact points to the possibility that activator activity might provide a useful index for evaluating the prognosis of cervical cancer. (author)

  5. Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis.

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    Yannan Fan

    Full Text Available The successive events that cells experience throughout development shape their intrinsic capacity to respond and integrate RTK inputs. Cellular responses to RTKs rely on different mechanisms of regulation that establish proper levels of RTK activation, define duration of RTK action, and exert quantitative/qualitative signalling outcomes. The extent to which cells are competent to deal with fluctuations in RTK signalling is incompletely understood. Here, we employ a genetic system to enhance RTK signalling in a tissue-specific manner. The chosen RTK is the hepatocyte growth factor (HGF receptor Met, an appropriate model due to its pleiotropic requirement in distinct developmental events. Ubiquitously enhanced Met in Cre/loxP-based Rosa26(stopMet knock-in context (Del-R26(Met reveals that most tissues are capable of buffering enhanced Met-RTK signalling thus avoiding perturbation of developmental programs. Nevertheless, this ubiquitous increase of Met does compromise selected programs such as myoblast migration. Using cell-type specific Cre drivers, we genetically showed that altered myoblast migration results from ectopic Met expression in limb mesenchyme rather than in migrating myoblasts themselves. qRT-PCR analyses show that ectopic Met in limbs causes molecular changes such as downregulation in the expression levels of Notum and Syndecan4, two known regulators of morphogen gradients. Molecular and functional studies revealed that ectopic Met expression in limb mesenchyme does not alter HGF expression patterns and levels, but impairs HGF bioavailability. Together, our findings show that myoblasts, in which Met is endogenously expressed, are capable of buffering increased RTK levels, and identify mesenchymal cells as a cell type vulnerable to ectopic Met-RTK signalling. These results illustrate that embryonic cells are sensitive to alterations in the spatial distribution of RTK action, yet resilient to fluctuations in signalling levels of an

  6. Evaluation of reference genes for quantitative real-time PCR in oil palm elite planting materials propagated by tissue culture.

    Directory of Open Access Journals (Sweden)

    Pek-Lan Chan

    Full Text Available BACKGROUND: The somatic embryogenesis tissue culture process has been utilized to propagate high yielding oil palm. Due to the low callogenesis and embryogenesis rates, molecular studies were initiated to identify genes regulating the process, and their expression levels are usually quantified using reverse transcription quantitative real-time PCR (RT-qPCR. With the recent release of oil palm genome sequences, it is crucial to establish a proper strategy for gene analysis using RT-qPCR. Selection of the most suitable reference genes should be performed for accurate quantification of gene expression levels. RESULTS: In this study, eight candidate reference genes selected from cDNA microarray study and literature review were evaluated comprehensively across 26 tissue culture samples using RT-qPCR. These samples were collected from two tissue culture lines and media treatments, which consisted of leaf explants cultures, callus and embryoids from consecutive developmental stages. Three statistical algorithms (geNorm, NormFinder and BestKeeper confirmed that the expression stability of novel reference genes (pOP-EA01332, PD00380 and PD00569 outperformed classical housekeeping genes (GAPDH, NAD5, TUBULIN, UBIQUITIN and ACTIN. PD00380 and PD00569 were identified as the most stably expressed genes in total samples, MA2 and MA8 tissue culture lines. Their applicability to validate the expression profiles of a putative ethylene-responsive transcription factor 3-like gene demonstrated the importance of using the geometric mean of two genes for normalization. CONCLUSIONS: Systematic selection of the most stably expressed reference genes for RT-qPCR was established in oil palm tissue culture samples. PD00380 and PD00569 were selected for accurate and reliable normalization of gene expression data from RT-qPCR. These data will be valuable to the research associated with the tissue culture process. Also, the method described here will facilitate the selection

  7. Evaluation of Reference Genes for Quantitative Real-Time PCR in Oil Palm Elite Planting Materials Propagated by Tissue Culture

    Science.gov (United States)

    Chan, Pek-Lan; Rose, Ray J.; Abdul Murad, Abdul Munir; Zainal, Zamri; Leslie Low, Eng-Ti; Ooi, Leslie Cheng-Li; Ooi, Siew-Eng; Yahya, Suzaini; Singh, Rajinder

    2014-01-01

    Background The somatic embryogenesis tissue culture process has been utilized to propagate high yielding oil palm. Due to the low callogenesis and embryogenesis rates, molecular studies were initiated to identify genes regulating the process, and their expression levels are usually quantified using reverse transcription quantitative real-time PCR (RT-qPCR). With the recent release of oil palm genome sequences, it is crucial to establish a proper strategy for gene analysis using RT-qPCR. Selection of the most suitable reference genes should be performed for accurate quantification of gene expression levels. Results In this study, eight candidate reference genes selected from cDNA microarray study and literature review were evaluated comprehensively across 26 tissue culture samples using RT-qPCR. These samples were collected from two tissue culture lines and media treatments, which consisted of leaf explants cultures, callus and embryoids from consecutive developmental stages. Three statistical algorithms (geNorm, NormFinder and BestKeeper) confirmed that the expression stability of novel reference genes (pOP-EA01332, PD00380 and PD00569) outperformed classical housekeeping genes (GAPDH, NAD5, TUBULIN, UBIQUITIN and ACTIN). PD00380 and PD00569 were identified as the most stably expressed genes in total samples, MA2 and MA8 tissue culture lines. Their applicability to validate the expression profiles of a putative ethylene-responsive transcription factor 3-like gene demonstrated the importance of using the geometric mean of two genes for normalization. Conclusions Systematic selection of the most stably expressed reference genes for RT-qPCR was established in oil palm tissue culture samples. PD00380 and PD00569 were selected for accurate and reliable normalization of gene expression data from RT-qPCR. These data will be valuable to the research associated with the tissue culture process. Also, the method described here will facilitate the selection of appropriate

  8. Detection and Interpretation of Fluorescence Signals Generated by Excitable Cells and Tissues

    Science.gov (United States)

    Costantino, Anthony J.

    Part 1: High-Sensitivity Amplifiers for Detecting Fluorescence . Monitoring electrical activity and Cai 2+ transients in biological tissues and individual cells increasingly utilizes optical sensors based on voltage-dependent and Cai 2+-dependent fluorescent dyes. However, achieving satisfactory signal-to-noise ratios (SNR) often requires increased illumination intensities and/or dye concentrations, which results in photo-toxicity, photo-bleaching and other adverse effects limiting the utility of optical recordings. The most challenging are the recordings from individual cardiac myocytes and neurons. Here we demonstrate that by optimizing a conventional transimpedance topology one can achieve a 10-20 fold increase of sensitivity with photodiode-based recording systems (dependent on application). We provide a detailed comparative analysis of the dynamic and noise characteristics of different transimpedance amplifier topologies as well as the example(s) of their practical implementation. Part 2: Light-Scattering Models for Interpretation of Fluorescence Data. Current interest in understanding light transport in cardiac tissue has been motivated in part by increased use of voltage-sensitive and Ca i2+-sensitive fluorescent probes to map electrical impulse propagation and Cai2+-transients in the heart. The fluorescent signals are recorded using such probes represent contributions from different layers of myocardial tissue and are greatly affected by light scattering. The interpretation of these signals thus requires deconvolution which would not be possible without detailed models of light transport in the respective tissue. Which involves the experimental measurements of the absorption, scattering, and anisotropy coefficients, mua, mu s, and g respectively. The aim of the second part of our thesis was to derive a new method for deriving these parameters from high spatial resolution measurements of forward-directed flux (FDF). To this end, we carried out high spatial

  9. Referred pain and cutaneous responses from deep tissue electrical pain stimulation in the groin

    DEFF Research Database (Denmark)

    Aasvang, E K; Werner, M U; Kehlet, H

    2015-01-01

    , supporting individual differences in anatomy and sensory processing. Future studies investigating the responses to deep tissue electrical stimulation in persistent postherniotomy pain patients may advance our understanding of underlying pathophysiological mechanisms and strategies for treatment...

  10. Characterization of in vitro healthy and pathological human liver tissue periodicity using backscattered ultrasound signals.

    Science.gov (United States)

    Machado, Christiano Bittencourt; Pereira, Wagner Coelho de Albuquerque; Meziri, Mahmoud; Laugier, Pascal

    2006-05-01

    This work studied the periodicity of in vitro healthy and pathologic liver tissue, using backscattered ultrasound (US) signals. It utilized the mean scatterer spacing (MSS) as a parameter of tissue characterization, estimated by three methods: the spectral autocorrelation (SAC), the singular spectrum analysis (SSA) and the quadratic transformation method (SIMON). The liver samples were classified in terms of tissue status using the METAVIR scoring system. Twenty tissue samples were classified in four groups: F0, F1, F3 and F4 (five samples for each). The Kolmogorov-Smirnov test (applied on group pairs) resulted as nonsignificant (p > 0.05) for two pairs only: F1/F3 (for SSA) and F3/F4 (for SAC). A discriminant analysis was applied using as parameters the MSS mean (MSS) and standard deviation (sigmaMSS), the estimates histogram mode (mMSS), and the speed of US (mc(foie)) in the medium, to evaluate the degree of discrimination among healthy and pathologic tissues. The better accuracy (Ac) with SAC (80%) was with parameter group (MSS, sigmaMSS, mc(foie)), achieving a sensitivity (Ss) of 92.3% and a specificity (Sp) of 57.1%. For SSA, the group with all four parameters showed an Ac of 75%, an Ss of 78.6% and an Sp of 66.70%. SIMON obtained the best Ac of all (85%) with group (MSS, mMSS, mc(foie)), an Ss of 100%, but with an Sp of 50%.

  11. Histopathological diagnostic discrepancies in soft tissue tumours referred to a specialist centre: reassessment in the era of ancillary molecular diagnosis.

    Science.gov (United States)

    Thway, Khin; Wang, Jayson; Mubako, Taka; Fisher, Cyril

    2014-01-01

    Introduction. Soft tissue tumour pathology is a highly specialised area of surgical pathology, but soft tissue neoplasms can occur at virtually all sites and are therefore encountered by a wide population of surgical pathologists. Potential sarcomas require referral to specialist centres for review by pathologists who see a large number of soft tissue lesions and where appropriate ancillary investigations can be performed. We have previously assessed the types of diagnostic discrepancies between referring and final diagnosis for soft tissue lesions referred to our tertiary centre. We now reaudit this 6 years later, assessing changes in discrepancy patterns, particularly in relation to the now widespread use of ancillary molecular diagnostic techniques which were not prevalent in our original study. Materials and Methods. We compared the sarcoma unit's histopathology reports with referring reports on 348 specimens from 286 patients with suspected or proven soft tissue tumours in a one-year period. Results. Diagnostic agreement was seen in 250 cases (71.8%), with 57 (16.4%) major and 41 (11.8%) minor discrepancies. There were 23 cases of benign/malignant discrepancies (23.5% of all discrepancies). 50 ancillary molecular tests were performed, 33 for aiding diagnosis and 17 mutational analyses for gastrointestinal stromal tumour to guide therapy. Findings from ancillary techniques contributed to 3 major and 4 minor discrepancies. While the results were broadly similar to those of the previous study, there was an increase in frequency of major discrepancies. Conclusion. Six years following our previous study and notably now in an era of widespread ancillary molecular diagnosis, the overall discrepancy rate between referral and tertiary centre diagnosis remains similar, but there is an increase in frequency of major discrepancies likely to alter patient management. A possible reason for the increase in major discrepancies is the increasing lack of exposure to soft tissue

  12. Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth; Bojsen-Moller, Kirstine N; Dirksen, Carsten

    2015-01-01

    Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose...... tolerant and type 2 diabetic subjects at fasting and during a hyperinsulinemic-euglycemic clamp before as well as 1 week, 3 and 12 months after RYGB were analyzed for relevant insulin effector proteins/signaling components. Improvement in peripheral insulin sensitivity mainly occurred at 12 months post-surgery...... and glycogen synthase activity were enhanced 12 months post-surgery. In adipose tissue, protein expression of GLUT4, Akt2, TBC1D4 and acetyl-CoA carboxylase (ACC), phosphorylated levels of AMP-activated protein kinase and ACC as well as insulin-induced changes in phosphorylation of Akt and TBC1D4 were enhanced...

  13. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Science.gov (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

  14. Reference-free determination of tissue absorption coefficient by modulation transfer function characterization in spatial frequency domain.

    Science.gov (United States)

    Chen, Weiting; Zhao, Huijuan; Li, Tongxin; Yan, Panpan; Zhao, Kuanxin; Qi, Caixia; Gao, Feng

    2017-08-08

    Spatial frequency domain (SFD) measurement allows rapid and non-contact wide-field imaging of the tissue optical properties, thus has become a potential tool for assessing physiological parameters and therapeutic responses during photodynamic therapy of skin diseases. The conventional SFD measurement requires a reference measurement within the same experimental scenario as that for a test one to calibrate mismatch between the real measurements and the model predictions. Due to the individual physical and geometrical differences among different tissues, organs and patients, an ideal reference measurement might be unavailable in clinical trials. To address this problem, we present a reference-free SFD determination of absorption coefficient that is based on the modulation transfer function (MTF) characterization. Instead of the absolute amplitude that is used in the conventional SFD approaches, we herein employ the MTF to characterize the propagation of the modulated lights in tissues. With such a dimensionless relative quantity, the measurements can be naturally corresponded to the model predictions without calibrating the illumination intensity. By constructing a three-dimensional database that portrays the MTF as a function of the optical properties (both the absorption coefficient μ a and the reduced scattering coefficient [Formula: see text]) and the spatial frequency, a look-up table approach or a least-square curve-fitting method is readily applied to recover the absorption coefficient from a single frequency or multiple frequencies, respectively. Simulation studies have verified the feasibility of the proposed reference-free method and evaluated its accuracy in the absorption recovery. Experimental validations have been performed on homogeneous tissue-mimicking phantoms with μ a ranging from 0.01 to 0.07 mm -1 and [Formula: see text] = 1.0 or 2.0 mm -1 . The results have shown maximum errors of 4.86 and 7% for [Formula: see text] = 1.0 mm -1 and

  15. Responses of the insulin signaling pathways in the brown adipose tissue of rats following cold exposure.

    Science.gov (United States)

    Wang, Xiaofei; Wahl, Richard

    2014-01-01

    The insulin signaling pathway is critical for the control of blood glucose levels. Brown adipose tissue (BAT) has also been implicated as important in glucose homeostasis. The effect of short-term cold exposure on this pathway in BAT has not been explored. We evaluated the effect of 4 hours of cold exposure on the insulin pathway in the BAT of rats. Whole genomic microarray chips were used to examine the transcripts of the pathway in BAT of rats exposed to 4°C and 22°C for 4 hours. The 4 most significantly altered pathways following 4 hours of cold exposure were the insulin signaling pathway, protein kinase A, PI3K/AKT and ERK/MAPK signaling. The insulin signaling pathway was the most affected. In the documented 142 genes of the insulin pathway, 42 transcripts (29.6%) responded significantly to this cold exposure with the least false discovery rate (Benjamini-Hochberg Multiple Testing: -log10 (p-value)  = 7.18). Twenty-seven genes (64%) were up-regulated, including the insulin receptor (Insr), insulin substrates 1 and 2 (Irs1 and Irs2). Fifteen transcripts (36%) were down-regulated. Multiple transcripts of the primary target and secondary effector targets for the insulin signaling were also up-regulated, including those for carbohydrate metabolism. Using western blotting, we demonstrated that the cold induced higher Irs2, Irs1, and Akt-p protein levels in the BAT than in the BAT of controls maintained at room temperature, and higher Akt-p protein level in the muscle. this study demonstrated that 4 hours of cold exposure stimulated the insulin signaling pathway in the BAT and muscle of overnight fasted rats. This raises the possibility that acute cold stimulation may have potential to improve glucose clearance and insulin sensitivity.

  16. MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells.

    Science.gov (United States)

    Jones, Russell G; Pearce, Edward J

    2017-05-16

    Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts. Copyright © 2017. Published by Elsevier Inc.

  17. Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells.

    Science.gov (United States)

    Falank, Carolyne; Fairfield, Heather; Reagan, Michaela R

    2016-01-01

    In the year 2000, Hanahan and Weinberg (1) defined the six Hallmarks of Cancer as: self-sufficiency in growth signals, evasion of apoptosis, insensitivity to antigrowth mechanisms, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis. Eleven years later, two new Hallmarks were added to the list (avoiding immune destruction and reprograming energy metabolism) and two new tumor characteristics (tumor-promoting inflammation and genome instability and mutation) (2). In multiple myeloma (MM), a destructive cancer of the plasma cell that grows predominantly in the bone marrow (BM), it is clear that all these hallmarks and characteristics are in play, contributing to tumor initiation, drug resistance, disease progression, and relapse. Bone marrow adipose tissue (BMAT) is a newly recognized contributor to MM oncogenesis and disease progression, potentially affecting MM cell metabolism, immune action, inflammation, and influences on angiogenesis. In this review, we discuss the confirmed and hypothetical contributions of BMAT to MM development and disease progression. BMAT has been understudied due to technical challenges and a previous lack of appreciation for the endocrine function of this tissue. In this review, we define the dynamic, responsive, metabolically active BM adipocyte. We then describe how BMAT influences MM in terms of: lipids/metabolism, hypoxia/angiogenesis, paracrine or endocrine signaling, and bone disease. We then discuss the connection between BMAT and systemic inflammation and potential treatments to inhibit the feedback loops between BM adipocytes and MM cells that support MM progression. We aim for researchers to use this review to guide and help prioritize their experiments to develop better treatments or a cure for cancers, such as MM, that associate with and may depend on BMAT.

  18. Selection of reference genes for gene expression studies in pig tissues using SYBR green qPCR

    DEFF Research Database (Denmark)

    Hillig, Ann-Britt Nygaard; Jørgensen, Claus Bøttcher; Cirera, Susanna

    2007-01-01

    -microglobulin (B2M), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hydroxymethylbilane synthase (HMBS), hypoxanthine phosphoribosyltransferase I (HPRT I), ribosomal protein L4 (RPL4), succinate dehydrogenase complex subunit A (SDHA), TATA box binding protein (TPB) and tyrosine 3-monooxygenase/tryptophan 5......-monooxygenase activation protein zeta polypeptide (YWHAZ). The stability of these reference genes in different pig tissues was investigated using the geNorm application. The range of expression stability in the genes analysed was (from the most stable to the least stable): ACTB/RPL4, TBP, HPRT, HMBS, YWHAZ...

  19. Identification of valid reference genes for the normalization of RT qPCR gene expression data in human brain tissue

    Directory of Open Access Journals (Sweden)

    Ravid Rivka

    2008-05-01

    Full Text Available Abstract Background Studies of gene expression in post mortem human brain can contribute to understanding of the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD, Parkinson's disease (PD and dementia with Lewy bodies (DLB. Quantitative real-time PCR (RT qPCR is often used to analyse gene expression. The validity of results obtained using RT qPCR is reliant on accurate data normalization. Reference genes are generally used to normalize RT qPCR data. Given that expression of some commonly used reference genes is altered in certain conditions, this study aimed to establish which reference genes were stably expressed in post mortem brain tissue from individuals with AD, PD or DLB. Results The present study investigated the expression stability of 8 candidate reference genes, (ubiquitin C [UBC], tyrosine-3-monooxygenase [YWHAZ], RNA polymerase II polypeptide [RP II], hydroxymethylbilane synthase [HMBS], TATA box binding protein [TBP], β-2-microglobulin [B2M], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], and succinate dehydrogenase complex-subunit A, [SDHA] in cerebellum and medial temporal gyrus of 6 AD, 6 PD, 6 DLB subjects, along with 5 matched controls using RT qPCR (TaqMan® Gene Expression Assays. Gene expression stability was analysed using geNorm to rank the candidate genes in order of decreasing stability in each disease group. The optimal number of genes recommended for accurate data normalization in each disease state was determined by pairwise variation analysis. Conclusion This study identified validated sets of mRNAs which would be appropriate for the normalization of RT qPCR data when studying gene expression in brain tissue of AD, PD, DLB and control subjects.

  20. Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic Tissue of Syrian Hamsters with Bicuspid Aortic Valve.

    Science.gov (United States)

    Rueda-Martínez, Carmen; Fernández, M Carmen; Soto-Navarrete, María Teresa; Jiménez-Navarro, Manuel; Durán, Ana Carmen; Fernández, Borja

    2016-01-01

    Bicuspid aortic valve (BAV) is the most frequent congenital cardiac malformation in humans, and appears frequently associated with dilatation of the ascending aorta. This association is likely the result of a common aetiology. Currently, a Syrian hamster strain with a relatively high (∼40%) incidence of BAV constitutes the only spontaneous animal model of BAV disease. The characterization of molecular alterations in the aorta of hamsters with BAV may serve to identify pathophysiological mechanisms and molecular markers of disease in humans. In this report, we evaluate the expression of ten candidate reference genes in aortic tissue of hamsters in order to identify housekeeping genes for normalization using quantitative real time PCR (RT-qPCR) assays. A total of 51 adult (180-240 days old) and 56 old (300-440 days old) animals were used. They belonged to a control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30), or to the affected strain of hamsters with TAV (n = 45) or BAV (n = 32). The expression stability of the candidate reference genes was determined by RT-qPCR using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable reference genes for the three algorithms employed were Cdkn1β, G3pdh and Polr2a. We propose the use of Cdkn1β, or both Cdkn1β and G3pdh as reference genes for mRNA expression analyses in Syrian hamster aorta.

  1. Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic Tissue of Syrian Hamsters with Bicuspid Aortic Valve.

    Directory of Open Access Journals (Sweden)

    Carmen Rueda-Martínez

    Full Text Available Bicuspid aortic valve (BAV is the most frequent congenital cardiac malformation in humans, and appears frequently associated with dilatation of the ascending aorta. This association is likely the result of a common aetiology. Currently, a Syrian hamster strain with a relatively high (∼40% incidence of BAV constitutes the only spontaneous animal model of BAV disease. The characterization of molecular alterations in the aorta of hamsters with BAV may serve to identify pathophysiological mechanisms and molecular markers of disease in humans. In this report, we evaluate the expression of ten candidate reference genes in aortic tissue of hamsters in order to identify housekeeping genes for normalization using quantitative real time PCR (RT-qPCR assays. A total of 51 adult (180-240 days old and 56 old (300-440 days old animals were used. They belonged to a control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30, or to the affected strain of hamsters with TAV (n = 45 or BAV (n = 32. The expression stability of the candidate reference genes was determined by RT-qPCR using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable reference genes for the three algorithms employed were Cdkn1β, G3pdh and Polr2a. We propose the use of Cdkn1β, or both Cdkn1β and G3pdh as reference genes for mRNA expression analyses in Syrian hamster aorta.

  2. Optimizing signal output: effects of viscoelasticity and difference frequency on vibroacoustic radiation of tissue-mimicking phantoms

    Science.gov (United States)

    Namiri, Nikan K.; Maccabi, Ashkan; Bajwa, Neha; Badran, Karam W.; Taylor, Zachary D.; St. John, Maie A.; Grundfest, Warren S.; Saddik, George N.

    2018-02-01

    Vibroacoustography (VA) is an imaging technology that utilizes the acoustic response of tissues to a localized, low frequency radiation force to generate a spatially resolved, high contrast image. Previous studies have demonstrated the utility of VA for tissue identification and margin delineation in cancer tissues. However, the relationship between specimen viscoelasticity and vibroacoustic emission remains to be fully quantified. This work utilizes the effects of variable acoustic wave profiles on unique tissue-mimicking phantoms (TMPs) to maximize VA signal power according to tissue mechanical properties, particularly elasticity. A micro-indentation method was utilized to provide measurements of the elastic modulus for each biological replica. An inverse relationship was found between elastic modulus (E) and VA signal amplitude among homogeneous TMPs. Additionally, the difference frequency (Δf ) required to reach maximum VA signal correlated with specimen elastic modulus. Peak signal diminished with increasing Δf among the polyvinyl alcohol specimen, suggesting an inefficient vibroacoustic response by the specimen beyond a threshold of resonant Δf. Comparison of these measurements may provide additional information to improve tissue modeling, system characterization, as well as insights into the unique tissue composition of tumors in head and neck cancer patients.

  3. Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin β-Receptor Signaling (LTβR) Originating from Splenic and Non-Splenic Tissues

    DEFF Research Database (Denmark)

    Milićević, Novica M; Nohroudi, Klaus; Schmidt, Friederike

    2016-01-01

    LTβR signaling. Two-dimensional differential gel electrophoresis and subsequent mass spectrometry of stromal splenic tissue was applied to screen for potential factors mediating the LTβR dependent suppressive activity. Thus, LTβR dependent growth suppression is involved in regulating the size...

  4. Coupling mechanical tension and GTPase signaling to generate cell and tissue dynamics

    Science.gov (United States)

    Zmurchok, Cole; Bhaskar, Dhananjay; Edelstein-Keshet, Leah

    2018-07-01

    Regulators of the actin cytoskeleton such Rho GTPases can modulate forces developed in cells by promoting actomyosin contraction. At the same time, through mechanosensing, tension is known to affect the activity of Rho GTPases. What happens when these effects act in concert? Using a minimal model (1 GTPase coupled to a Kelvin–Voigt element), we show that two-way feedback between signaling (‘RhoA’) and mechanical tension (stretching) leads to a spectrum of cell behaviors, including contracted or relaxed cells, and cells that oscillate between these extremes. When such ‘model cells’ are connected to one another in a row or in a 2D sheet (‘epithelium’), we observe waves of contraction/relaxation and GTPase activity sweeping through the tissue. The minimal model lends itself to full bifurcation analysis, and suggests a mechanism that explains behavior observed in the context of development and collective cell behavior.

  5. White adipose tissue IFN-γ expression and signalling along the progression of rodent cancer cachexia.

    Science.gov (United States)

    Yamashita, Alex Shimura; das Neves, Rodrigo Xavier; Rosa-Neto, José Cesar; Lira, Fábio Dos Santos; Batista, Miguel Luís; Alcantara, Paulo Sérgio; Otoch, José Pinhata; Seelaender, Marília

    2017-01-01

    Cachexia is associated with increased morbidity and mortality in cancer. The White adipose tissue (WAT) synthesizes and releases several pro-inflammatory cytokines that play a role in cancer cachexia-related systemic inflammation. IFN-γ is a pleiotropic cytokine that regulates several immune and metabolic functions. To assess whether IFN-γ signalling in different WAT pads is modified along cancer-cachexia progression, we evaluated IFN-γ receptors expression (IFNGR1 and IFNGR2) and IFN-γ protein expression in a rodent model of cachexia (7, 10, and 14days after tumour implantation). IFN-γ protein expression was heterogeneously modulated in WAT, with increases in the mesenteric pad and decreased levels in the retroperitoneal depot along cachexia progression. Ifngr1 was up-regulated 7days after tumour cell injection in mesenteric and epididymal WAT, but the retroperitoneal depot showed reduced Ifngr1 gene expression. Ifngr2 gene expression was increased 7 and 14days after tumour inoculation in mesenteric WAT. The results provide evidence that changes in IFN-γ expression and signalling may be perceived at stages preceding refractory cachexia, and therefore, might be employed as a means to assess the early stage of the syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Chapter 10 the primary cilium coordinates signaling pathways in cell cycle control and migration during development and tissue repair

    DEFF Research Database (Denmark)

    Christensen, Søren T; Pedersen, Stine F; Satir, Peter

    2008-01-01

    Cell cycle control and migration are critical processes during development and maintenance of tissue functions. Recently, primary cilia were shown to take part in coordination of the signaling pathways that control these cellular processes in human health and disease. In this review, we present...... an overview of the function of primary cilia and the centrosome in the signaling pathways that regulate cell cycle control and migration with focus on ciliary signaling via platelet-derived growth factor receptor alpha (PDGFRalpha). We also consider how the primary cilium and the centrosome interact...... with the extracellular matrix, coordinate Wnt signaling, and modulate cytoskeletal changes that impinge on both cell cycle control and cell migration....

  7. Insulin Signaling in Liver and Adipose Tissues in Periparturient Dairy Cows Supplemented with Dietary Nicotinic Acid.

    Science.gov (United States)

    Kinoshita, Asako; Kenéz, Ákos; Locher, Lena; Meyer, Ulrich; Dänicke, Sven; Rehage, Jürgen; Huber, Korinna

    2016-01-01

    The glucose homeostasis in dairy cattle is very well controlled, in line with the metabolic adaptation during the periparturient period. Former studies showed that nicotinic acid (NA) lowered plasma non-esterified fatty acids (NEFA) concentrations and increased insulin sensitivity in dairy cows. Thus, the purpose of this study was to investigate whether the expression of proteins involved in hepatic and adipose insulin signaling and protein expression of hepatic glucose transporter 2 (GLUT2) were affected by dietary NA and dietary concentrate intake in periparturient dairy cows. Twenty pluriparous German Holstein cows were fed with the same diet from about 21 days before the expected calving date (d-21) to calving. After calving, cows were randomly assigned in 4 groups and fed with diets different in concentrate proportion ("HC" with 60:40% or "LC" with 30:70% concentrate-to-roughage ratio) and supplemented with NA (24 g/day) (NA) or without (CON) until d21. Biopsy samples were taken from the liver, subcutaneous (SCAT) and retroperitoneal (RPAT) adipose tissues at d-21 and d21. Protein expression of insulin signaling molecules (insulin receptor (INSR), phosphatidylinositol-3-kinase (PI3K), protein kinase Cζ (PKCζ)) and hepatic GLUT2 was measured by Western Blotting. The ratio of protein expression at d21/at d-21 was calculated and statistically evaluated for the effects of time and diet. Cows in HC had significantly higher dietary energy intake than cows in LC. In RPAT a decrease in PI3K and PKCζ expression was found in all groups, irrespectively of diet. In the liver, the GLUT2 expression was significantly lower in cows in NA compared with cows in CON. In conclusion, insulin signaling might be decreased in RPAT over time without any effect of diet. NA was able to modulate hepatic GLUT2 expression, but its physiological role is unclear.

  8. Insulin Signaling in Liver and Adipose Tissues in Periparturient Dairy Cows Supplemented with Dietary Nicotinic Acid.

    Directory of Open Access Journals (Sweden)

    Asako Kinoshita

    Full Text Available The glucose homeostasis in dairy cattle is very well controlled, in line with the metabolic adaptation during the periparturient period. Former studies showed that nicotinic acid (NA lowered plasma non-esterified fatty acids (NEFA concentrations and increased insulin sensitivity in dairy cows. Thus, the purpose of this study was to investigate whether the expression of proteins involved in hepatic and adipose insulin signaling and protein expression of hepatic glucose transporter 2 (GLUT2 were affected by dietary NA and dietary concentrate intake in periparturient dairy cows. Twenty pluriparous German Holstein cows were fed with the same diet from about 21 days before the expected calving date (d-21 to calving. After calving, cows were randomly assigned in 4 groups and fed with diets different in concentrate proportion ("HC" with 60:40% or "LC" with 30:70% concentrate-to-roughage ratio and supplemented with NA (24 g/day (NA or without (CON until d21. Biopsy samples were taken from the liver, subcutaneous (SCAT and retroperitoneal (RPAT adipose tissues at d-21 and d21. Protein expression of insulin signaling molecules (insulin receptor (INSR, phosphatidylinositol-3-kinase (PI3K, protein kinase Cζ (PKCζ and hepatic GLUT2 was measured by Western Blotting. The ratio of protein expression at d21/at d-21 was calculated and statistically evaluated for the effects of time and diet. Cows in HC had significantly higher dietary energy intake than cows in LC. In RPAT a decrease in PI3K and PKCζ expression was found in all groups, irrespectively of diet. In the liver, the GLUT2 expression was significantly lower in cows in NA compared with cows in CON. In conclusion, insulin signaling might be decreased in RPAT over time without any effect of diet. NA was able to modulate hepatic GLUT2 expression, but its physiological role is unclear.

  9. Reference hearing threshold levels for chirp signals delivered by an ER-3A insert earphone

    DEFF Research Database (Denmark)

    Gøtsche-Rasmussen, Kristian; Poulsen, Torben; Elberling, Claus

    2012-01-01

    back from a Tucker Davies Technologies System II, and a Matlab program controlled the test setup. The results are specified in dB peak-to-peak equivalent threshold sound pressure levels (dB peETSPL). Study sample: The test group consisted of 25 otologically-normal young adults (age 18–25 years......Objective: To establish reference hearing threshold levels for chirps and frequency-specific chirps. Design: Hearing thresholds were determined monaurally for broad-band chirps and octave-band chirps using the Etymotic Research, ER-3A insert earphone. The chirps were presented using two repetition...

  10. Impact of the choice of the precipitation reference data set on climate model selection and the resulting climate change signal

    Science.gov (United States)

    Gampe, D.; Ludwig, R.

    2017-12-01

    Regional Climate Models (RCMs) that downscale General Circulation Models (GCMs) are the primary tool to project future climate and serve as input to many impact models to assess the related changes and impacts under such climate conditions. Such RCMs are made available through the Coordinated Regional climate Downscaling Experiment (CORDEX). The ensemble of models provides a range of possible future climate changes around the ensemble mean climate change signal. The model outputs however are prone to biases compared to regional observations. A bias correction of these deviations is a crucial step in the impact modelling chain to allow the reproduction of historic conditions of i.e. river discharge. However, the detection and quantification of model biases are highly dependent on the selected regional reference data set. Additionally, in practice due to computational constraints it is usually not feasible to consider the entire ensembles of climate simulations with all members as input for impact models which provide information to support decision-making. Although more and more studies focus on model selection based on the preservation of the climate model spread, a selection based on validity, i.e. the representation of the historic conditions is still a widely applied approach. In this study, several available reference data sets for precipitation are selected to detect the model bias for the reference period 1989 - 2008 over the alpine catchment of the Adige River located in Northern Italy. The reference data sets originate from various sources, such as station data or reanalysis. These data sets are remapped to the common RCM grid at 0.11° resolution and several indicators, such as dry and wet spells, extreme precipitation and general climatology, are calculate to evaluate the capability of the RCMs to produce the historical conditions. The resulting RCM spread is compared against the spread of the reference data set to determine the related uncertainties and

  11. Abnormal Wnt signaling and stem cell activation in reactive lymphoid tissue and low-grade marginal zone lymphoma.

    Science.gov (United States)

    Zhang, Da; O'neil, Maura F; Cunningham, Mark T; Fan, Fang; Olyaee, Mojtaba; Li, Linheng

    2010-05-01

    The variable natural history of mucosa-associated lymphoid tissue (MALT) lymphoma poses a challenge in predicting clinical outcome. Since Wnt signaling, as indicated by nuclear localization of beta-catenin, is believed to be key in stem cell activation and stem cell self-renewal, we explored the possibility that it might have a predictive value in marginal zone lymphoma. We chose to analyze pbeta-catenin-S552 because its nuclear localization by immunohistochemistry appears to coincide with Wnt signaling-initiated tumorigenesis in intestinal and hematopoietic tissues. Wnt signaling and activation was studied in 22 tissue samples of extranodal marginal zone lymphoma, atypical lymphoid hyperplasia, reactive lymphoid hyperplasia, and normal lymphoid tissue to determine whether Wnt signaling could help distinguish MALT lymphoma from benign lesions. Compared to normal or reactive lymphoid tissue, we found increased nuclear expression of localized pbeta-catenin-S552 in atypical lymphoid hyperplasia and extranodal marginal zone lymphoma. We show that the anti-pbeta-catenin-S552 antibody may be useful in diagnosing and monitoring the progression of or response to therapy of MALT lymphoma.

  12. Preparation, characterization and use of a reference material to proficiency testing for determination of metals in fish tissue in natura

    International Nuclear Information System (INIS)

    Santana, Luciana Vieira de

    2013-01-01

    The proficiency tests are widely used to evaluate the analytical capacity of laboratories and also as part of the accreditation process. For this reason, are important tools for the control of the quality of the analytical results obtained in the laboratories that work directly with seafood companies. In Brazil there are no providers of proficiency testing for metals potentially toxic in fish tissues. In this work will be described all steps used for the production of reference materials to be used in a proficiency testing pilot study for As, Cd, Pb and Hg in fish tissue following the recommendations of the ISO Guide 35. He preparation scheme consisted in selecting the individuals, cleaning, grinding, homogenization and fortification with As, Cd and Pb in two concentration levels. The preparation resulted in 164 sachets of 10 g each. In order to evaluate the effect of gamma irradiation in the samples conservation 52 sachets were irradiated with 60 Co (10.00 ± 1.05 kGy) in a gamma cell. This material with others non irradiated 52 sachets were used for the homogeneity and stability studies. The remaining 60 were used for the proficiency testing. The results demonstrated that both materials were homogeneous and presented good stability (during a period of 45 days). However, the irradiated material present better integrity, concerning biological degradation, when stored in ambient temperature. For this reason they were used to the proficiency testing pilot program. Ten laboratories participated in the proficiency testing pilot study and the results were evaluated using the following tests: z-score, confidence ellipse and En numbers. This work demonstrates the capability of the laboratory to produce reference materials as well as to organize and conduct proficiency testing. (author)

  13. Brassica napus seed endosperm - metabolism and signaling in a dead end tissue.

    Science.gov (United States)

    Lorenz, Christin; Rolletschek, Hardy; Sunderhaus, Stephanie; Braun, Hans-Peter

    2014-08-28

    Oilseeds are an important element of human nutrition and of increasing significance for the production of industrial materials. The development of the seeds is based on a coordinated interplay of the embryo and its surrounding tissue, the endosperm. This study aims to give insights into the physiological role of endosperm for seed development in the oilseed crop Brassica napus. Using protein separation by two-dimensional (2D) isoelectric focusing (IEF)/SDS polyacrylamide gel electrophoresis (PAGE) and protein identification by mass spectrometry three proteome projects were carried out: (i) establishment of an endosperm proteome reference map, (ii) proteomic characterization of endosperm development and (iii) comparison of endosperm and embryo proteomes. The endosperm proteome reference map comprises 930 distinct proteins, including enzymes involved in genetic information processing, carbohydrate metabolism, environmental information processing, energy metabolism, cellular processes and amino acid metabolism. To investigate dynamic changes in protein abundance during seed development, total soluble proteins were extracted from embryo and endosperm fractions at defined time points. Proteins involved in sugar converting and recycling processes, ascorbate metabolism, amino acid biosynthesis and redox balancing were found to be of special importance for seed development in B. napus. Implications for the seed filling process and the function of the endosperm for seed development are discussed. The endosperm is of key importance for embryo development during seed formation in plants. We present a broad study for characterizing endosperm proteins in the oilseed plant B. napus. Furthermore, a project on the biochemical interplay between the embryo and the endosperm during seed development is presented. We provide evidence that the endosperm includes a complete set of enzymes necessary for plant primary metabolism. Combination of our results with metabolome data will further

  14. Insulin signaling displayed a differential tissue-specific response to low-dose dihydrotestosterone in female mice.

    Science.gov (United States)

    Andrisse, Stanley; Billings, Katelyn; Xue, Ping; Wu, Sheng

    2018-04-01

    Hyperandrogenemia and hyperinsulinemia are believed to play prominent roles in polycystic ovarian syndrome (PCOS). We explored the effects of low-dose dihydrotestosterone (DHT), a model of PCOS, on insulin signaling in metabolic and reproductive tissues in a female mouse model. Insulin resistance in the energy storage tissues is associated with type 2 diabetes. Insulin signaling in the ovaries and pituitary either directly or indirectly stimulates androgen production. Energy storage and reproductive tissues were isolated and molecular assays were performed. Livers and white adipose tissue (WAT) from DHT mice displayed lower mRNA and protein expression of insulin signaling intermediates. However, ovaries and pituitaries of DHT mice exhibited higher expression levels of insulin signaling genes/proteins. Insulin-stimulated p-AKT levels were blunted in the livers and WAT of the DHT mice but increased or remained the same in the ovaries and pituitaries compared with controls. Glucose uptake decreased in liver and WAT but was unchanged in pituitary and ovary of DHT mice. Plasma membrane GLUTs were decreased in liver and WAT but increased in ovary and pituitary of DHT mice. Skeletal muscle insulin-signaling genes were not lowered in DHT mice compared with control. DHT mice did not display skeletal muscle insulin resistance. Insulin-stimulated glucose transport increased in skeletal muscles of DHT mice compared with controls. DHT mice were hyperinsulinemic. However, the differential mRNA and protein expression pattern was independent of hyperinsulinemia in cultured hepatocytes and pituitary cells. These findings demonstrate a differential effect of DHT on the insulin-signaling pathway in energy storage vs. reproductive tissues independent of hyperinsulinemia.

  15. In vivo cyclic loading as a potent stimulatory signal for bone formation inside tissue engineering scaffold

    Directory of Open Access Journals (Sweden)

    A Roshan-Ghias

    2010-02-01

    Full Text Available In clinical situations, bone defects are often located at load bearing sites. Tissue engineering scaffolds are future bone substitutes and hence they will be subjected to mechanical stimulation. The goal of this study was to test if cyclic loading can be used as stimulatory signal for bone formation in a bone scaffold. Poly(L-lactic acid (PLA/ 5% beta-tricalcium phosphate (beta-TCP scaffolds were implanted in both distal femoral epiphyses of eight rats. Right knees were stimulated (10N, 4Hz, 5 min five times, every two days, starting from the third day after surgery while left knees served as control. Finite element study of the in vivo model showed that the strain applied to the scaffold is similar to physiological strains. Using micro-computed tomography (CT, all knees were scanned five times after the surgery and the related bone parameters of the newly formed bone were quantified. Statistical modeling was used to estimate the evolution of these parameters as a function of time and loading. The results showed that mechanical stimulation had two effects on bone volume (BV: an initial decrease in BV at week 2, and a long-term increase in the rate of bone formation by 28%. At week 13, the BV was then significantly higher in the loaded scaffolds.

  16. Structural organization of the thyroid gland and interrenal tissue with reference to endocrine parenchyma in short mackerel, Rastrelliger brachysoma (Bleeker, 1851

    Directory of Open Access Journals (Sweden)

    Sinlapachai Senarat

    2016-01-01

    Full Text Available The first investigations of the thyroid gland and interrenal tissue with reference to the endocrine parenchyma of short mackerel Rastrelliger brachysoma were subjected to histological analysis. Specimens were collected during the fishing season (October to November 2013 from the Upper Gulf of Thailand. Under a light microscope, the thyroid gland of R. brachysoma was distinctly found located within the branchial region. Within this gland, it consists of several follicles among afferent brachial arteries. Each follicle exclusively contained a colloid that was surrounded by a simple, cuboidal, follicle epithelium. Histological study showed that the localization of interrenal tissue was in the anterior kidney. This tissue was composed of two parts based on the structural compositions and cell types; (i the stromal compartment was constituted of various interrenal cells and (ii the interstitial compartment contained the connective tissue, leucocytes and blood sinuses, with reference to the lymphatic tissue.

  17. ESR signal features of 60Co γ-ray irradiated bone tissue and its dose response relationship

    International Nuclear Information System (INIS)

    Wu Ke; Sun Zunpu; Shi Yuanming

    1993-01-01

    Electron spin resonance (ESR) technique was used to study the radiation-induced ESR signal features of different paramagnetic species of 60 Co γ-ray irradiated bone tissue. The results showed that the intensity of an ESR signal at that the intensity of an ESR signal at g 2.0022 of human bones exposed to a dose range of 0-50 Gy had linear dose response relationships. The lower limit of detectable dose was about 2 Gy and the detecting error was about 10%. The signal was stable at room temperature during 60 days, and the effect of radiation dose rate of 0.5-8.0 Gy/min could be neglected. This signal was insensitive to microwave power and temperature, which was suitable for rapid and direct detection with ESR technique. These features suggest that human bones could be used for radiation accident dose evaluation by ESR

  18. Selection of suitable reference genes for normalization of genes of interest in canine soft tissue sarcomas using quantitative real-time polymerase chain reaction

    DEFF Research Database (Denmark)

    Zornhagen, K. W.; Kristensen, A. T.; Hansen, Anders Elias

    2015-01-01

    Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) is a sensitive technique for quantifying gene expression. Stably expressed reference genes are necessary for normalization of RT-qPCR data. Only a few articles have been published on reference genes in canine tumours....... The objective of this study was to demonstrate how to identify suitable reference genes for normalization of genes of interest in canine soft tissue sarcomas using RT-qPCR. Primer pairs for 17 potential reference genes were designed and tested in archival tumour biopsies from six dogs. The geNorm algorithm...

  19. Bipartite recognition of DNA by TCF/Pangolin is remarkably flexible and contributes to transcriptional responsiveness and tissue specificity of wingless signaling.

    Directory of Open Access Journals (Sweden)

    Hilary C Archbold

    2014-09-01

    Full Text Available The T-cell factor (TCF family of transcription factors are major mediators of Wnt/β-catenin signaling in metazoans. All TCFs contain a High Mobility Group (HMG domain that possesses specific DNA binding activity. In addition, many TCFs contain a second DNA binding domain, the C-clamp, which binds to DNA motifs referred to as Helper sites. While HMG and Helper sites are both important for the activation of several Wnt dependent cis-regulatory modules (W-CRMs, the rules of what constitutes a functional HMG-Helper site pair are unknown. In this report, we employed a combination of in vitro binding, reporter gene analysis and bioinformatics to address this question, using the Drosophila family member TCF/Pangolin (TCF/Pan as a model. We found that while there were constraints for the orientation and spacing of HMG-Helper pairs, the presence of a Helper site near a HMG site in any orientation increased binding and transcriptional response, with some orientations displaying tissue-specific patterns. We found that altering an HMG-Helper site pair from a sub-optimal to optimal orientation/spacing dramatically increased the responsiveness of a W-CRM in several fly tissues. In addition, we used the knowledge gained to bioinformatically identify two novel W-CRMs, one that was activated by Wnt/β-catenin signaling in the prothoracic gland, a tissue not previously connected to this pathway. In sum, this work extends the importance of Helper sites in fly W-CRMs and suggests that the type of HMG-Helper pair is a major factor in setting the threshold for Wnt activation and tissue-responsiveness.

  20. Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration.

    Science.gov (United States)

    Martino, Mikaël M; Maruyama, Kenta; Kuhn, Gisela A; Satoh, Takashi; Takeuchi, Osamu; Müller, Ralph; Akira, Shizuo

    2016-03-22

    Tissue injury and the healing response lead to the release of endogenous danger signals including Toll-like receptor (TLR) and interleukin-1 receptor, type 1 (IL-1R1) ligands, which modulate the immune microenvironment. Because TLRs and IL-1R1 have been shown to influence the repair process of various tissues, we explored their role during bone regeneration, seeking to design regenerative strategies integrating a control of their signalling. Here we show that IL-1R1/MyD88 signalling negatively regulates bone regeneration, in the mouse. Furthermore, IL-1β which is released at the bone injury site, inhibits the regenerative capacities of mesenchymal stem cells (MSCs). Mechanistically, IL-1R1/MyD88 signalling impairs MSC proliferation, migration and differentiation by inhibiting the Akt/GSK-3β/β-catenin pathway. Lastly, as a proof of concept, we engineer a MSC delivery system integrating inhibitors of IL-1R1/MyD88 signalling. Using this strategy, we considerably improve MSC-based bone regeneration in the mouse, demonstrating that this approach may be useful in regenerative medicine applications.

  1. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  2. Validation of reference genes for gene expression analysis in olive (Olea europaea) mesocarp tissue by quantitative real-time RT-PCR

    Science.gov (United States)

    2014-01-01

    Background Gene expression analysis using quantitative reverse transcription PCR (qRT-PCR) is a robust method wherein the expression levels of target genes are normalised using internal control genes, known as reference genes, to derive changes in gene expression levels. Although reference genes have recently been suggested for olive tissues, combined/independent analysis on different cultivars has not yet been tested. Therefore, an assessment of reference genes was required to validate the recent findings and select stably expressed genes across different olive cultivars. Results A total of eight candidate reference genes [glyceraldehyde 3-phosphate dehydrogenase (GAPDH), serine/threonine-protein phosphatase catalytic subunit (PP2A), elongation factor 1 alpha (EF1-alpha), polyubiquitin (OUB2), aquaporin tonoplast intrinsic protein (TIP2), tubulin alpha (TUBA), 60S ribosomal protein L18-3 (60S RBP L18-3) and polypyrimidine tract-binding protein homolog 3 (PTB)] were chosen based on their stability in olive tissues as well as in other plants. Expression stability was examined by qRT-PCR across 12 biological samples, representing mesocarp tissues at various developmental stages in three different olive cultivars, Barnea, Frantoio and Picual, independently and together during the 2009 season with two software programs, GeNorm and BestKeeper. Both software packages identified GAPDH, EF1-alpha and PP2A as the three most stable reference genes across the three cultivars and in the cultivar, Barnea. GAPDH, EF1-alpha and 60S RBP L18-3 were found to be most stable reference genes in the cultivar Frantoio while 60S RBP L18-3, OUB2 and PP2A were found to be most stable reference genes in the cultivar Picual. Conclusions The analyses of expression stability of reference genes using qRT-PCR revealed that GAPDH, EF1-alpha, PP2A, 60S RBP L18-3 and OUB2 are suitable reference genes for expression analysis in developing Olea europaea mesocarp tissues, displaying the highest level

  3. Certification of methylmercury in cod fish tissue certified reference material by species-specific isotope dilution mass spectrometric analysis

    Energy Technology Data Exchange (ETDEWEB)

    Inagaki, Kazumi; Kuroiwa, Takayoshi; Narukawa, Tomohiro; Yarita, Takashi; Takatsu, Akiko; Okamoto, Kensaku; Chiba, Koichi [National Metrology Institute of Japan (NMIJ), National Institute of Advanced Industrial Science and Technology (AIST), Environmental Standard Section, Tsukuba, Ibaraki (Japan)

    2008-07-15

    A new cod fish tissue certified reference material, NMIJ CRM 7402-a, for methylmercury analysis was certified by the National Metrological Institute of Japan in the National Institute of Advanced Industrial Science and Technology (NMIJ/AIST). Cod fish was collected from the sea close to Japan. The cod muscle was powdered by freeze-pulverization and was placed into 600 glass bottles (10 g each), which were sterilized with {gamma}-ray irradiation. The certification was carried out using species-specific isotope dilution gas chromatography inductively coupled plasma mass spectrometry (SSID-GC-ICPMS), where {sup 202}Hg-enriched methylmercury (MeHg) was used as the spike compound. In order to avoid any possible analytical biases caused by nonquantitative extraction, degradation and/or formation of MeHg in sample preparations, two different extraction methods (KOH/methanol and HCl/methanol extractions) were performed, and one of these extraction methods utilized two different derivatization methods (ethylation and phenylation). A double ID method was adopted to minimize the uncertainty arising from the analyses. In order to ensure not only the reliability of the analytical results but also traceability to SI units, the standard solution of MeHg used for the reverse-ID was prepared from high-purity MeHg chloride and was carefully assayed as follows: the total mercury was determined by ID-ICPMS following aqua regia digestion, and the ratio of Hg as MeHg to the total Hg content was estimated by GC-ICPMS. The certified value given for MeHg is 0.58 {+-} 0.02 mg kg{sup -1} as Hg. (orig.)

  4. Selection of reference genes for quantitative RT-PCR (RT-qPCR) analysis of rat tissues under physiological and toxicological conditions

    DEFF Research Database (Denmark)

    Svingen, Terje; Letting, Heidi; Hadrup, Niels

    2015-01-01

    In biological research the analysis of gene expression levels in cells and tissues can be a powerful tool to gain insights into biological processes. For this, quantitative RT-PCR (RT-qPCR) is a popular method that often involve the use of constitutively expressed endogenous reference (or...... ‘housekeeping’) gene for normalization of data. Thus, it is essential to use reference genes that have been verified to be stably expressed within the specific experimental setting. Here, we have analysed the expression stability of 12 commonly used reference genes (Actb, B2m, Gapdh, Hprt, Pgk1, Rn18s, Rpl13a...

  5. Analysis of factors causing signal loss in the measurement of lung tissue water by nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Fukuzaki, Minoru; Shioya, Sumie; Haida, Munetaka

    1997-01-01

    The water content of lung, brain, and muscle tissue was measured by nuclear magnetic resonance (NMR) and compared with gravimetric determinations. The NMR signal intensity of water was measured by a single 90 degree pulse and by a spin-echo sequence. The absolute water content was determined by the difference in the sample's weight before and after desiccation. The NMR detectable water in each tissue was expressed as a percentage of the signal intensity for an equal weight of distilled water. Using the single pulse measurement, 67% of the gravimetrically-measured water was detected in collapsed lung samples (consisting of about 47% retained air), in contrast to 96% for brain and 98% for muscle. For degassed lung samples, the NMR detectability of water increased to 87% with the single pulse measurement and to 90% with the spin-echo measurement, but the values remained significantly less than those of brain or muscle. Factors that caused the NMR signal loss of 33% in collapsed lung samples were: air-tissue interfaces (20%), microscopic field inhomogeneity (3%), and a water component with an extremely short magnetization decay time constant (10%). (author)

  6. Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

    Science.gov (United States)

    van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

    2012-10-01

    The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

  7. Tissue Architecture and Microenvironment Sustain Hormone Signaling | Center for Cancer Research

    Science.gov (United States)

    Cells interact with their environments in part through protein receptors embedded in the cell membrane. Activation of a receptor by external signaling molecules sets off a complex chain of events within the cell that can result in alterations in protein structure and function and/or changes in gene expression. Proper integration of these signals is crucial for normal cell

  8. Biomaterials in co-culture systems: towards optimizing tissue integration and cell signaling within scaffolds.

    Science.gov (United States)

    Battiston, Kyle G; Cheung, Jane W C; Jain, Devika; Santerre, J Paul

    2014-05-01

    Most natural tissues consist of multi-cellular systems made up of two or more cell types. However, some of these tissues may not regenerate themselves following tissue injury or disease without some form of intervention, such as from the use of tissue engineered constructs. Recent studies have increasingly used co-cultures in tissue engineering applications as these systems better model the natural tissues, both physically and biologically. This review aims to identify the challenges of using co-culture systems and to highlight different approaches with respect to the use of biomaterials in the use of such systems. The application of co-culture systems to stimulate a desired biological response and examples of studies within particular tissue engineering disciplines are summarized. A description of different analytical co-culture systems is also discussed and the role of biomaterials in the future of co-culture research are elaborated on. Understanding the complex cell-cell and cell-biomaterial interactions involved in co-culture systems will ultimately lead the field towards biomaterial concepts and designs with specific biochemical, electrical, and mechanical characteristics that are tailored towards the needs of distinct co-culture systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Evaluation of signal intensity of various thyroid tissues on MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Koichiro; Imanishi, Yoshimasa [St. Marianna Univ., Kawasaki, Kanagawa (Japan). School of Medicine; Igarashi, Ryuukou; Shinagawa, Toshihito

    2001-08-01

    Although normal thyroid mainly consists of thyroid follicles and has large amount of water in them, it shows low signal intensity on T2 weighted MR image. In this paper, we analysed the signal intensity of the thyroid in clinical cases and investigated the relationship between signal intensity and iodine concentration. In forty-one patients who have clinically suspected thyroid diseases, fifty-three MRI examinations of the neck and forty-three thyroid CT examinations were performed. The MR imaging of the neck was performed with T1 weighted image, T2 weighted image, and STIR image. Iodine concentration of the thyroid was measured by the CT software which was originally made by one of the authors (Y.I.). The signal intensity on T2 weighted image negatively correlated with iodine concentration, although there was no relationship between iodine concentration and its signal intensity on T1 weighted image. On T2 weighted image, the intensity of thyroid with high iodine concentration showed a low signal and that of thyroid with low iodine concentration presented a high signal. The thyroid with chronic thyroiditis showed higher signal intensity than normal thyroid and adenmatous goiter on T2 weighted image and STIR image. On T2 weighted image and STIR image, the signal intensity of any thyroid nodules were higher than that of normal thyroid. In addition, follicular adenoma and partially malignant nodules showed a higher signal intensity than thyroid carcinomas. According to previous reports, decreased iodine concentration in thyroid follicles represents decreased concentration of iodine-binding proteins in follicles as well as decreased volume of follicular content in the thyroid. On MR imaging, very high concentration of protein in water solution does not only cause shortening of T1 relaxation time but also shortening of T2 relaxation time resulting in low signal intensity. In the present study, our data seem to suggest that very high concentration of iodine

  10. Evaluation of signal intensity of various thyroid tissues on MR imaging

    International Nuclear Information System (INIS)

    Baba, Koichiro; Imanishi, Yoshimasa; Igarashi, Ryuukou; Shinagawa, Toshihito

    2001-01-01

    Although normal thyroid mainly consists of thyroid follicles and has large amount of water in them, it shows low signal intensity on T2 weighted MR image. In this paper, we analysed the signal intensity of the thyroid in clinical cases and investigated the relationship between signal intensity and iodine concentration. In forty-one patients who have clinically suspected thyroid diseases, fifty-three MRI examinations of the neck and forty-three thyroid CT examinations were performed. The MR imaging of the neck was performed with T1 weighted image, T2 weighted image, and STIR image. Iodine concentration of the thyroid was measured by the CT software which was originally made by one of the authors (Y.I.). The signal intensity on T2 weighted image negatively correlated with iodine concentration, although there was no relationship between iodine concentration and its signal intensity on T1 weighted image. On T2 weighted image, the intensity of thyroid with high iodine concentration showed a low signal and that of thyroid with low iodine concentration presented a high signal. The thyroid with chronic thyroiditis showed higher signal intensity than normal thyroid and adenmatous goiter on T2 weighted image and STIR image. On T2 weighted image and STIR image, the signal intensity of any thyroid nodules were higher than that of normal thyroid. In addition, follicular adenoma and partially malignant nodules showed a higher signal intensity than thyroid carcinomas. According to previous reports, decreased iodine concentration in thyroid follicles represents decreased concentration of iodine-binding proteins in follicles as well as decreased volume of follicular content in the thyroid. On MR imaging, very high concentration of protein in water solution does not only cause shortening of T1 relaxation time but also shortening of T2 relaxation time resulting in low signal intensity. In the present study, our data seem to suggest that very high concentration of iodine

  11. Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

    Science.gov (United States)

    Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

    2014-12-01

    Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. © 2014 The Authors.

  12. Epithelial–stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues

    Science.gov (United States)

    Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

    2014-01-01

    Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj—a gene encoding a transcription factor implicated in Notch signaling—in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. Subject Categories Development & Differentiation; Immunology; Signal Transduction PMID:25378482

  13. Reference gene selection for quantitative gene expression studies during biological invasions: A test on multiple genes and tissues in a model ascidian Ciona savignyi.

    Science.gov (United States)

    Huang, Xuena; Gao, Yangchun; Jiang, Bei; Zhou, Zunchun; Zhan, Aibin

    2016-01-15

    As invasive species have successfully colonized a wide range of dramatically different local environments, they offer a good opportunity to study interactions between species and rapidly changing environments. Gene expression represents one of the primary and crucial mechanisms for rapid adaptation to local environments. Here, we aim to select reference genes for quantitative gene expression analysis based on quantitative Real-Time PCR (qRT-PCR) for a model invasive ascidian, Ciona savignyi. We analyzed the stability of ten candidate reference genes in three tissues (siphon, pharynx and intestine) under two key environmental stresses (temperature and salinity) in the marine realm based on three programs (geNorm, NormFinder and delta Ct method). Our results demonstrated only minor difference for stability rankings among the three methods. The use of different single reference gene might influence the data interpretation, while multiple reference genes could minimize possible errors. Therefore, reference gene combinations were recommended for different tissues - the optimal reference gene combination for siphon was RPS15 and RPL17 under temperature stress, and RPL17, UBQ and TubA under salinity treatment; for pharynx, TubB, TubA and RPL17 were the most stable genes under temperature stress, while TubB, TubA and UBQ were the best under salinity stress; for intestine, UBQ, RPS15 and RPL17 were the most reliable reference genes under both treatments. Our results suggest that the necessity of selection and test of reference genes for different tissues under varying environmental stresses. The results obtained here are expected to reveal mechanisms of gene expression-mediated invasion success using C. savignyi as a model species. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. The use of laser microdissection in the identification of suitable reference genes for normalization of quantitative real-time PCR in human FFPE epithelial ovarian tissue samples.

    Directory of Open Access Journals (Sweden)

    Jing Cai

    Full Text Available Quantitative real-time PCR (qPCR is a powerful and reproducible method of gene expression analysis in which expression levels are quantified by normalization against reference genes. Therefore, to investigate the potential biomarkers and therapeutic targets for epithelial ovarian cancer by qPCR, it is critical to identify stable reference genes. In this study, twelve housekeeping genes (ACTB, GAPDH, 18S rRNA, GUSB, PPIA, PBGD, PUM1, TBP, HRPT1, RPLP0, RPL13A, and B2M were analyzed in 50 ovarian samples from normal, benign, borderline, and malignant tissues. For reliable results, laser microdissection (LMD, an effective technique used to prepare homogeneous starting material, was utilized to precisely excise target tissues or cells. One-way analysis of variance (ANOVA and nonparametric (Kruskal-Wallis tests were used to compare the expression differences. NormFinder and geNorm software were employed to further validate the suitability and stability of the candidate genes. Results showed that epithelial cells occupied a small percentage of the normal ovary indeed. The expression of ACTB, PPIA, RPL13A, RPLP0, and TBP were stable independent of the disease progression. In addition, NormFinder and geNorm identified the most stable combination (ACTB, PPIA, RPLP0, and TBP and the relatively unstable reference gene GAPDH from the twelve commonly used housekeeping genes. Our results highlight the use of homogeneous ovarian tissues and multiple-reference normalization strategy, e.g. the combination of ACTB, PPIA, RPLP0, and TBP, for qPCR in epithelial ovarian tissues, whereas GAPDH, the most commonly used reference gene, is not recommended, especially as a single reference gene.

  15. The use of laser microdissection in the identification of suitable reference genes for normalization of quantitative real-time PCR in human FFPE epithelial ovarian tissue samples.

    Science.gov (United States)

    Cai, Jing; Li, Tao; Huang, Bangxing; Cheng, Henghui; Ding, Hui; Dong, Weihong; Xiao, Man; Liu, Ling; Wang, Zehua

    2014-01-01

    Quantitative real-time PCR (qPCR) is a powerful and reproducible method of gene expression analysis in which expression levels are quantified by normalization against reference genes. Therefore, to investigate the potential biomarkers and therapeutic targets for epithelial ovarian cancer by qPCR, it is critical to identify stable reference genes. In this study, twelve housekeeping genes (ACTB, GAPDH, 18S rRNA, GUSB, PPIA, PBGD, PUM1, TBP, HRPT1, RPLP0, RPL13A, and B2M) were analyzed in 50 ovarian samples from normal, benign, borderline, and malignant tissues. For reliable results, laser microdissection (LMD), an effective technique used to prepare homogeneous starting material, was utilized to precisely excise target tissues or cells. One-way analysis of variance (ANOVA) and nonparametric (Kruskal-Wallis) tests were used to compare the expression differences. NormFinder and geNorm software were employed to further validate the suitability and stability of the candidate genes. Results showed that epithelial cells occupied a small percentage of the normal ovary indeed. The expression of ACTB, PPIA, RPL13A, RPLP0, and TBP were stable independent of the disease progression. In addition, NormFinder and geNorm identified the most stable combination (ACTB, PPIA, RPLP0, and TBP) and the relatively unstable reference gene GAPDH from the twelve commonly used housekeeping genes. Our results highlight the use of homogeneous ovarian tissues and multiple-reference normalization strategy, e.g. the combination of ACTB, PPIA, RPLP0, and TBP, for qPCR in epithelial ovarian tissues, whereas GAPDH, the most commonly used reference gene, is not recommended, especially as a single reference gene.

  16. E4orf1 induction in adipose tissue promotes insulin-independent signaling in the adipocyte

    Directory of Open Access Journals (Sweden)

    Christine M. Kusminski

    2015-10-01

    Conclusion: We conclude that E4orf1 expression in the adipocyte leads to enhanced baseline activation of the distal insulin signaling node, yet impaired insulin receptor stimulation in the presence of insulin, with important implications for the regulation of adiponectin secretion. The resulting systemic phenotype is complex, yet highlights the powerful nature of manipulating selective branches of the insulin signaling network within the adipocyte.

  17. Evaluation of Appropriate Reference Genes for Reverse Transcription-Quantitative PCR Studies in Different Tissues of a Desert Poplar via Comparision of Different Algorithms

    Directory of Open Access Journals (Sweden)

    Hou-Ling Wang

    2015-08-01

    Full Text Available Despite the unshakable status of reverse transcription-quantitative PCR in gene expression analysis, it has certain disadvantages, including that the results are highly dependent on the reference genes selected for data normalization. Since inappropriate endogenous control genes will lead to inaccurate target gene expression profiles, the validation of suitable internal reference genes is essential. Given the increasing interest in functional genes and genomics of Populus euphratica, a desert poplar showing extraordinary adaptation to salt stress, we evaluated the expression stability of ten candidate reference genes in P. euphratica roots, stems, and leaves under salt stress conditions. We used five algorithms, namely, ΔCt, NormFinder, geNorm, GrayNorm, and a rank aggregation method (RankAggreg to identify suitable normalizers. To support the suitability of the identified reference genes and to compare the relative merits of these different algorithms, we analyzed and compared the relative expression levels of nine P. euphratica functional genes in different tissues. Our results indicate that a combination of multiple reference genes recommended by GrayNorm algorithm (e.g., a combination of Actin, EF1α, GAPDH, RP, UBQ in root should be used instead of a single reference gene. These results are valuable for research of gene identification in different P. euphratica tissues.

  18. Effect of Peroral Administration of Chromium on Insulin Signaling Pathway in Skeletal Muscle Tissue of Holstein Calves.

    Science.gov (United States)

    Jovanović, Ljubomir; Pantelić, Marija; Prodanović, Radiša; Vujanac, Ivan; Đurić, Miloje; Tepavčević, Snežana; Vranješ-Đurić, Sanja; Korićanac, Goran; Kirovski, Danijela

    2017-12-01

    The objective of this study was to investigate the effects of peroral administration of chromium-enriched yeast on glucose tolerance in Holstein calves, assessed by insulin signaling pathway molecule determination and intravenous glucose tolerance test (IVGTT). Twenty-four Holstein calves, aged 1 month, were chosen for the study and divided into two groups: the PoCr group (n = 12) that perorally received 0.04 mg of Cr/kg of body mass daily, for 70 days, and the NCr group (n = 12) that received no chromium supplementation. Skeletal tissue samples from each calf were obtained on day 0 and day 70 of the experiment. Chromium supplementation increased protein content of the insulin β-subunit receptor, phosphorylation of insulin receptor substrate 1 at Tyrosine 632, phosphorylation of Akt at Serine 473, glucose transporter-4, and AMP-activated protein kinase in skeletal muscle tissue, while phosphorylation of insulin receptor substrate 1 at Serine 307 was not affected by chromium treatment. Results obtained during IVGTT, which was conducted on days 0, 30, 50, and 70, suggested an increased insulin sensitivity and, consequently, a better utilization of glucose in the PoCr group. Lower basal concentrations of glucose and insulin in the PoCr group on days 30 and 70 were also obtained. Our results indicate that chromium supplementation improves glucose utilization in calves by enhancing insulin intracellular signaling in the skeletal muscle tissue.

  19. Cap-n-Collar Promotes Tissue Regeneration by Regulating ROS and JNK Signaling in the Drosophila melanogaster Wing Imaginal Disc.

    Science.gov (United States)

    Brock, Amanda R; Seto, Mabel; Smith-Bolton, Rachel K

    2017-07-01

    Regeneration is a complex process that requires an organism to recognize and repair tissue damage, as well as grow and pattern new tissue. Here, we describe a genetic screen to identify novel regulators of regeneration. We ablated the Drosophila melanogaster larval wing primordium by inducing apoptosis in a spatially and temporally controlled manner and allowed the tissue to regenerate and repattern. To identify genes that regulate regeneration, we carried out a dominant-modifier screen by assessing the amount and quality of regeneration in adult wings heterozygous for isogenic deficiencies. We have identified 31 regions on the right arm of the third chromosome that modify the regenerative response. Interestingly, we observed several distinct phenotypes: mutants that regenerated poorly, mutants that regenerated faster or better than wild-type, and mutants that regenerated imperfectly and had patterning defects. We mapped one deficiency region to cap-n-collar ( cnc ), the Drosophila Nrf2 ortholog, which is required for regeneration. Cnc regulates reactive oxygen species levels in the regenerating epithelium, and affects c-Jun N-terminal protein kinase (JNK) signaling, growth, debris localization, and pupariation timing. Here, we present the results of our screen and propose a model wherein Cnc regulates regeneration by maintaining an optimal level of reactive oxygen species to promote JNK signaling. Copyright © 2017 by the Genetics Society of America.

  20. Depletion of white adipose tissue in cancer cachexia syndrome is associated with inflammatory signaling and disrupted circadian regulation.

    Directory of Open Access Journals (Sweden)

    Maria Tsoli

    Full Text Available Involuntary weight loss in patients with cancer is the hallmark of cancer cachexia. The etiology of cachexia is multifactorial involving loss of skeletal muscle and adipose tissue associated with high systemic levels of acute phase proteins and inflammatory cytokines. While muscle wasting overtly impacts on cancer patient quality of life, loss of lipid depots represents a sustained energy imbalance. In this study fat depletion was examined in Colon-26 model of cancer cachexia, which is a widely used rodent model of this syndrome. We investigated diurnal expression of circadian rhythm regulators as well as key mediators of energy metabolism and cytokine signaling. Mice bearing the C26 tumour exhibited reduced adipose mass, elevated adipose tissue lipolysis and a 5-fold increase in plasma levels of free fatty acids. These changes were associated with activated IL-6 signaling in WAT through a 3-fold increase in phosphorylated STAT3 and high SOCS3 gene expression levels. In addition perturbations in circadian regulation of lipid metabolism were also observed. Lipid catabolism did not appear to be influenced by the classical PKA pathway activating the lipase HSL. ATGL protein levels were elevated 2-fold in cachectic mice while 4-fold increase phosphorylated ACC and a 2-fold decrease in phosphorylated 4EBP1 was observed indicating that lipid metabolism is modulated by the ATGL & AMPK/mTOR pathways. This study provides evidence for activation of cytokine signaling and concomitant alterations in circadian rhythm and regulators of lipid metabolism in WAT of cachectic animals.

  1. Stem development through vascular tissues: EPFL-ERECTA family signaling that bounces in and out of phloem.

    Science.gov (United States)

    Tameshige, Toshiaki; Ikematsu, Shuka; Torii, Keiko U; Uchida, Naoyuki

    2017-01-01

    Plant cells communicate with each other using a variety of signaling molecules. Recent studies have revealed that various types of secreted peptides, as well as phytohormones known since long ago, mediate cell-cell communication in diverse contexts of plant life. These peptides affect cellular activities, such as proliferation and cell fate decisions, through their perception by cell surface receptors located on the plasma membrane of target cells. ERECTA (ER), an Arabidopsis thaliana receptor kinase gene, was first identified as a stem growth regulator, and since then an increasing number of studies have shown that ER is involved in a wide range of developmental and physiological processes. In particular, molecular functions of ER have been extensively studied in stomatal patterning. Furthermore, the importance of ER signaling in vascular tissues of inflorescence stems, especially in phloem cells, has recently been highlighted. In this review article, first we briefly summarize the history of ER research including studies on stomatal development, then introduce ER functions in vascular tissues, and discuss its interactions with phytohormones and other receptor kinase signaling pathways. Future questions and challenges will also be addressed. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain.

    Directory of Open Access Journals (Sweden)

    Nick Van Laeken

    Full Text Available This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT, obtained via the one- and two- tissue compartment model (1-TC, 2-TC and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC. For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722. Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs.

  3. The AKT-mTOR signalling pathway in kidney cancer tissues

    Science.gov (United States)

    Spirina, L. V.; Usynin, Y. A.; Kondakova, I. V.; Yurmazov, Z. A.; Slonimskaya, E. M.; Kolegova, E. S.

    2015-11-01

    An increased expression of phospho-AKT, m-TOR, glycogen regulator GSK-3-beta and transcription inhibitor 4E-BP1 was observed in kidney cancer tissues. Tumor size growth was associated with a high level of c-Raf and low content of phospho-m-TOR. Cancer metastasis development led to a decreased PTEN and phospho-AKT expression.

  4. Inhibition of Notch signaling by Dll4-Fc promotes reperfusion of acutely ischemic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ren [Department of Pathology, University of Southern California, Los Angeles (United States); Trindade, Alexandre [Centro Interdisciplinar de Investigacao em Sanidade Animal (CIISA), Lisbon Technical University, Lisbon (Portugal); Instituto Gulbenkian de Ciencia, Oeiras (Portugal); Sun, Zhanfeng [Department of Vascular Surgery, 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang (China); Kumar, Ram; Weaver, Fred A. [Department of Surgery, University of Southern California, Los Angeles (United States); Krasnoperov, Valery; Naga, Kranthi [Vasgene Therapeutics, Los Angeles, CA (United States); Duarte, Antonio [Centro Interdisciplinar de Investigacao em Sanidade Animal (CIISA), Lisbon Technical University, Lisbon (Portugal); Instituto Gulbenkian de Ciencia, Oeiras (Portugal); Gill, Parkash S., E-mail: parkashg@usc.edu [Department of Pathology, University of Southern California, Los Angeles (United States)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Low dose Dll4-Fc increases vascular proliferation and overall perfusion. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in hindlimb ischemia model. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in skin flap model. Black-Right-Pointing-Pointer Dll4 heterozygous deletion promotes vascular injury recovery. Black-Right-Pointing-Pointer Dll4 overexpression delays vascular injury recovery. -- Abstract: Notch pathway regulates vessel development and maturation. Dll4, a high-affinity ligand for Notch, is expressed predominantly in the arterial endothelium and is induced by hypoxia among other factors. Inhibition of Dll4 has paradoxical effects of reducing the maturation and perfusion in newly forming vessels while increasing the density of vessels. We hypothesized that partial and/or intermittent inhibition of Dll4 may lead to increased vascular response and still allow vascular maturation to occur. Thus tissue perfusion can be restored rapidly, allowing quicker recovery from ischemia or tissue injury. Our studies in two different models (hindlimb ischemia and skin flap) show that inhibition of Dll4 at low dose allows faster recovery from vascular and tissue injury. This opens a new possibility for Dll4 blockade's therapeutic application in promoting recovery from vascular injury and restoring blood supply to ischemic tissues.

  5. High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

    International Nuclear Information System (INIS)

    Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

    2012-01-01

    Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

  6. Selection of reference genes is critical for miRNA expression analysis in human cardiac tissue. A focus on atrial fibrillation.

    Science.gov (United States)

    Masè, Michela; Grasso, Margherita; Avogaro, Laura; D'Amato, Elvira; Tessarolo, Francesco; Graffigna, Angelo; Denti, Michela Alessandra; Ravelli, Flavia

    2017-01-24

    MicroRNAs (miRNAs) are emerging as key regulators of complex biological processes in several cardiovascular diseases, including atrial fibrillation (AF). Reverse transcription-quantitative polymerase chain reaction is a powerful technique to quantitatively assess miRNA expression profile, but reliable results depend on proper data normalization by suitable reference genes. Despite the increasing number of studies assessing miRNAs in cardiac disease, no consensus on the best reference genes has been reached. This work aims to assess reference genes stability in human cardiac tissue with a focus on AF investigation. We evaluated the stability of five reference genes (U6, SNORD48, SNORD44, miR-16, and 5S) in atrial tissue samples from eighteen cardiac-surgery patients in sinus rhythm and AF. Stability was quantified by combining BestKeeper, delta-C q , GeNorm, and NormFinder statistical tools. All methods assessed SNORD48 as the best and U6 as the worst reference gene. Applications of different normalization strategies significantly impacted miRNA expression profiles in the study population. Our results point out the necessity of a consensus on data normalization in AF studies to avoid the emergence of divergent biological conclusions.

  7. Looking Beyond the Genes: The Interplay Between Signaling Pathways and Mechanics in the Shaping and Diversification of Epithelial Tissues.

    Science.gov (United States)

    Urdy, S; Goudemand, N; Pantalacci, S

    2016-01-01

    The core of Evo-Devo lies in the intuition that the way tissues grow during embryonic development, the way they sustain their structure and function throughout lifetime, and the way they evolve are closely linked. Epithelial tissues are ubiquitous in metazoans, covering the gut and internal branched organs, as well as the skin and its derivatives (ie, teeth). Here, we discuss in vitro, in vivo, and in silico studies on epithelial tissues to illustrate the conserved, dynamical, and complex aspects of their development. We then explore the implications of the dynamical and nonlinear nature of development on the evolution of their size and shape at the phenotypic and genetic levels. In rare cases, when the interplay between signaling and mechanics is well understood at the cell level, it is becoming clear that the structure of development leads to covariation of characters, an integration which in turn provides some predictable structure to evolutionary changes. We suggest that such nonlinear systems are prone to genetic drift, cryptic genetic variation, and context-dependent mutational effects. We argue that experimental and theoretical studies at the cell level are critical to our understanding of the phenotypic and genetic evolution of epithelial tissues, including carcinomas. © 2016 Elsevier Inc. All rights reserved.

  8. Anterior Gradient 2 (AGR2) Induced Epidermal Growth Factor Receptor (EGFR) Signaling Is Essential for Murine Pancreatitis-Associated Tissue Regeneration

    Science.gov (United States)

    Wodziak, Dariusz; Dong, Aiwen; Basin, Michael F.; Lowe, Anson W.

    2016-01-01

    A recently published study identified Anterior Gradient 2 (AGR2) as a regulator of EGFR signaling by promoting receptor presentation from the endoplasmic reticulum to the cell surface. AGR2 also promotes tissue regeneration in amphibians and fish. Whether AGR2-induced EGFR signaling is essential for tissue regeneration in higher vertebrates was evaluated using a well-characterized murine model for pancreatitis. The impact of AGR2 expression and EGFR signaling on tissue regeneration was evaluated using the caerulein-induced pancreatitis mouse model. EGFR signaling and cell proliferation were examined in the context of the AGR2-/- null mouse or with the EGFR-specific tyrosine kinase inhibitor, AG1478. In addition, the Hippo signaling coactivator YAP1 was evaluated in the context of AGR2 expression during pancreatitis. Pancreatitis-induced AGR2 expression enabled EGFR translocation to the plasma membrane, the initiation of cell signaling, and cell proliferation. EGFR signaling and tissue regeneration were partially inhibited by the tyrosine kinase inhibitor AG1478, but absent in the AGR2-/- null mouse. AG1478-treated and AGR2-/- null mice with pancreatitis died whereas all wild-type controls recovered. YAP1 activation was also dependent on pancreatitis-induced AGR2 expression. AGR2-induced EGFR signaling was essential for tissue regeneration and recovery from pancreatitis. The results establish tissue regeneration as a major function of AGR2-induced EGFR signaling in adult higher vertebrates. Enhanced AGR2 expression and EGFR signaling are also universally present in human pancreatic cancer, which support a linkage between tissue injury, regeneration, and cancer pathogenesis. PMID:27764193

  9. Selection of suitable reference genes for normalization of genes of interest in canine soft tissue sarcomas using quantitative real-time polymerase chain reaction.

    Science.gov (United States)

    Zornhagen, K W; Kristensen, A T; Hansen, A E; Oxboel, J; Kjaer, A

    2015-12-01

    Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) is a sensitive technique for quantifying gene expression. Stably expressed reference genes are necessary for normalization of RT-qPCR data. Only a few articles have been published on reference genes in canine tumours. The objective of this study was to demonstrate how to identify suitable reference genes for normalization of genes of interest in canine soft tissue sarcomas using RT-qPCR. Primer pairs for 17 potential reference genes were designed and tested in archival tumour biopsies from six dogs. The geNorm algorithm was used to analyse the most suitable reference genes. Eight potential reference genes were excluded from this final analysis because of their dissociation curves. β-Glucuronidase (GUSB) and proteasome subunit, beta type, 6 (PSMB6) were most stably expressed with an M value of 0.154 and a CV of 0.053 describing their average stability. We suggest that choice of reference genes should be based on specific testing in every new experimental set-up. © 2014 John Wiley & Sons Ltd.

  10. Intracellular co-delivery of Sr ion and phenamil drug through mesoporous bioglass nanocarriers synergizes BMP signaling and tissue mineralization.

    Science.gov (United States)

    Lee, Jung-Hwan; Mandakhbayar, Nandin; El-Fiqi, Ahmed; Kim, Hae-Won

    2017-09-15

    Inducing differentiation and maturation of resident multipotent stem cells (MSCs) is an important strategy to regenerate hard tissues in mal-calcification conditions. Here we explore a co-delivery approach of therapeutic molecules comprised of ion and drug through a mesoporous bioglass nanoparticle (MBN) for this purpose. Recently, MBN has offered unique potential as a nanocarrier for hard tissues, in terms of high mesoporosity, bone bioactivity (and possibly degradability), tunable delivery of biomolecules, and ionic modification. Herein Sr ion is structurally doped to MBN while drug Phenamil is externally loaded as a small molecule activator of BMP signaling, for the stimulation of osteo/odontogenesis and mineralization of human MSCs derived from dental pulp. The Sr-doped MBN (85Si:10Ca:5Sr) sol-gel processed presents a high mesoporosity with a pore size of ∼6nm. In particular, Sr ion is released slowly at a daily rate of ∼3ppm per mg nanoparticles for up to 7days, a level therapeutically effective for cellular stimulation. The Sr-MBN is internalized to most MSCs via an ATP dependent macropinocytosis within hours, increasing the intracellular levels of Sr, Ca and Si ions. Phenamil is loaded maximally ∼30% into Sr-MBN and then released slowly for up to 7days. The co-delivered molecules (Sr ion and Phenamil drug) have profound effects on the differentiation and maturation of cells, i.e., significantly enhancing expression of osteo/odontogenic genes, alkaline phosphatase activity, and mineralization of cells. Of note, the stimulation is a result of a synergism of Sr and Phenamil, through a Trb3-dependent BMP signaling pathway. This biological synergism is further evidenced in vivo in a mal-calcification condition involving an extracted tooth implantation in dorsal subcutaneous tissues of rats. Six weeks post operation evidences the osseous-dentinal hard tissue formation, which is significantly stimulated by the Sr/Phenamil delivery, based on histomorphometric

  11. Defocused low-energy shock wave activates adipose tissue-derived stem cells in vitro via multiple signaling pathways.

    Science.gov (United States)

    Xu, Lina; Zhao, Yong; Wang, Muwen; Song, Wei; Li, Bo; Liu, Wei; Jin, Xunbo; Zhang, Haiyang

    2016-12-01

    We found defocused low-energy shock wave (DLSW) could be applied in regenerative medicine by activating mesenchymal stromal cells. However, the possible signaling pathways that participated in this process remain unknown. In the present study, DLSW was applied in cultured rat adipose tissue-derived stem cells (ADSCs) to explore its effect on ADSCs and the activated signaling pathways. After treating with DLSW, the cellular morphology and cytoskeleton of ADSCs were observed. The secretions of ADSCs were detected. The expressions of ADSC surface antigens were analyzed using flow cytometry. The expressions of proliferating cell nuclear antigen and Ki67 were analyzed using western blot. The expression of CXCR2 and the migrations of ADSCs in vitro and in vivo were detected. The phosphorylation of selected signaling pathways with or without inhibitors was also detected. DLSW did not change the morphology and phenotype of ADSCs, and could promote the secretion, proliferation and migration of ADSCs. The phosphorylation levels were significantly higher in mitogen-activated protein kinases (MAPK) pathway, phosphoinositide 3-kinase (PI-3K)/AKT pathway and nuclear factor-kappa B (NF-κB) signaling pathway but not in Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Furthermore, ADSCs were not activated by DLSW after adding the inhibitors of these pathways simultaneously. Our results demonstrated for the first time that DLSW could activate ADSCs through MAPK, PI-3K/AKT and NF-κB signaling pathways. Combination of DLSW and agonists targeting these pathways might improve the efficacy of ADSCs in regenerative medicine in the future. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  12. Wound trauma mediated inflammatory signaling attenuates a tissue regenerative response in MRL/MpJ mice

    Directory of Open Access Journals (Sweden)

    Elster Eric A

    2010-05-01

    Full Text Available Abstract Background Severe trauma can induce pathophysiological responses that have marked inflammatory components. The development of systemic inflammation following severe thermal injury has been implicated in immune dysfunction, delayed wound healing, multi-system organ failure and increased mortality. Methods In this study, we examined the impact of thermal injury-induced systemic inflammation on the healing response of a secondary wound in the MRL/MpJ mouse model, which was anatomically remote from the primary site of trauma, a wound that typically undergoes scarless healing in this specific strain. Ear-hole wounds in MRL/MpJ mice have previously displayed accelerated healing and tissue regeneration in the absence of a secondary insult. Results Severe thermal injury in addition to distal ear-hole wounds induced marked local and systemic inflammatory responses in the lungs and significantly augmented the expression of inflammatory mediators in the ear tissue. By day 14, 61% of the ear-hole wounds from thermally injured mice demonstrated extensive inflammation with marked inflammatory cell infiltration, extensive ulceration, and various level of necrosis to the point where a large percentage (38% had to be euthanized early during the study due to extensive necrosis, inflammation and ear deformation. By day 35, ear-hole wounds in mice not subjected to thermal injury were completely closed, while the ear-hole wounds in thermally injured mice exhibited less inflammation and necrosis and only closed partially (62%. Thermal injury resulted in marked increases in serum levels of IL-6, TNFα, KC (CXCL1, and MIP-2α (CXCL2. Interestingly, attenuated early ear wound healing in the thermally injured mouse resulted in incomplete tissue regeneration in addition to a marked inflammatory response, as evidenced by the histological appearance of the wound and increased transcription of potent inflammatory mediators. Conclusion These findings suggest that the

  13. Short-and long-term glucocorticoid treatment enhances insulin signalling in human subcutaneous adipose tissue

    OpenAIRE

    Gathercole, LL; Morgan, SA; Bujalska, IJ; Stewart, PM; Tomlinson, JW

    2011-01-01

    Background: Endogenous or exogenous glucocorticoid (GC) excess (Cushing's syndrome) is characterized by increased adiposity and insulin resistance. Although GCs cause global insulin resistance in vivo, we have previously shown that GCs are able to augment insulin action in human adipose tissue, contrasting with their action in skeletal muscle. Cushing's syndrome develops following chronic GC exposure and, in addition, is a state of hyperinsulinemia. Objectives: We have therefore compared the ...

  14. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples.

    Science.gov (United States)

    Gorelick, Daniel A; Iwanowicz, Luke R; Hung, Alice L; Blazer, Vicki S; Halpern, Marnie E

    2014-04-01

    Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ERα was expressed in developing heart valves but not in the liver, whereas ERβ2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

  15. Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2018-01-01

    Full Text Available Wound healing is a complex process that involves sequential phases that overlap in time and space and affect each other dynamically at the gene and protein levels. We previously showed that insulin accelerates wound healing by stimulating faster and regenerative healing. One of the processes that insulin stimulates is an increase in monocyte/macrophage chemotaxis. In this study, we performed experiments in vivo and in vitro to elucidate the signaling transduction pathways that are involved in insulin-induced monocyte/macrophage chemotaxis. We found that insulin stimulates THP-1 cell chemotaxis in a dose-dependent and insulin receptor-dependent manner. We also show that the kinases PI3K-Akt, SPAK/JNK, and p38 MAPK are key molecules in the insulin-induced signaling pathways that lead to chemoattraction of the THP-1 cell. Furthermore, both PI3K-Akt and SPAK/JNK signaling involve Rac1 activation, an important molecule in regulating cell motility. Indeed, topical application of Rac1 inhibitor at an early stage during the healing process caused delayed and impaired healing even in the presence of insulin. These results delineate cell and molecular mechanisms involved in insulin-induced chemotaxis of monocyte/macrophage, cells that are critical for proper healing.

  16. [Dinitrosyl iron complexes are endogenous signaling agents in animal and human cells and tissues (a hypothesis)].

    Science.gov (United States)

    Vanin, A F

    2004-01-01

    The hypothesis was advanced that dinitrosyl iron complexes generated in animal and human cells and tissues producing nitric oxide can function as endogenous universal regulators of biochemical and physiological processes. This function is realized by the ability of dinitrosyl iron complexes to act as donors of free nitric oxide molecules interacting with the heme groups of proteins, nitrosonium ions, or Fe+(NO+)2 interacting with the thiol groups of proteins. The effect of dinitrosyl iron complexes on the activity of some enzymes and the expression of the genome at the translation and transcription levels was considered.

  17. Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue.

    Science.gov (United States)

    Liu, Zhenjiang; Gan, Lu; Xu, Yatao; Luo, Dan; Ren, Qian; Wu, Song; Sun, Chao

    2017-08-01

    Pyroptosis is a proinflammatory form of cell death that is associated with pathogenesis of many chronic inflammatory diseases. Melatonin is substantially reported to possess anti-inflammatory properties by inhibiting inflammasome activation. However, the effects of melatonin on inflammasome-induced pyroptosis in adipocytes remain elusive. Here, we demonstrated that melatonin alleviated lipopolysaccharides (LPS)-induced inflammation and NLRP3 inflammasome formation in mice adipose tissue. The NLRP3 inflammasome-mediated pyroptosis was also inhibited by melatonin in adipocytes. Further analysis revealed that gasdermin D (GSDMD), the key executioner of pyroptosis, was the target for melatonin inhibition of adipocyte pyroptosis. Importantly, we determined that nuclear factor κB (NF-κB) signal was required for the GSDMD-mediated pyroptosis in adipocytes. We also confirmed that melatonin alleviated adipocyte pyroptosis by transcriptional suppression of GSDMD. Moreover, GSDMD physically interacted with interferon regulatory factor 7 (IRF7) and subsequently formed a complex to promote adipocyte pyroptosis. Melatonin also attenuated NLRP3 inflammasome activation and pyroptosis, which was induced by LPS or obesity. In summary, our results demonstrate that melatonin alleviates inflammasome-induced pyroptosis by blocking NF-κB/GSDMD signal in mice adipose tissue. Our data reveal a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Reference values for the Chinese population of skin autofluorescence as a marker of advanced glycation end products accumulated in tissue

    NARCIS (Netherlands)

    Yue, X.; Hu, H.; Koetsier, M.; Graaff, R.; Han, C.

    Aim Advanced glycation end products play an important role in the pathophysiology of several chronic and age-related diseases, especially diabetes mellitus. Skin autofluorescence is a non-invasive method for assessing levels of tissue advanced glycation end products. This study aims to establish the

  19. Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory Responses in the Liver and White Adipose Tissue.

    Directory of Open Access Journals (Sweden)

    Mohamed Asrih

    Full Text Available Beside its beneficial effects on weight loss, ketogenic diet (KD causes dyslipidemia, a pro-inflammatory state involved in the development of hepatic steatosis, glucose intolerance and insulin resistance, although the latter is still being debated. Additionally, KD is known to increase fibroblast growth factor 21 (FGF21 plasma levels. However, FGF21 cannot initiate its beneficial actions on metabolism in these conditions. We therefore hypothesized and tested in the present study that KD may impair FGF21 signaling.Using indirect calorimetry, we found that KD-fed mice exhibited higher energy expenditure than regular chow (RC-fed mice associated with increased Ucp1 levels in white adipose tissue (WAT, along with increased plasma FGF21 levels. We then assessed the effect of KD on FGF21 signaling in both the liver and WAT. We found that Fgfr4 and Klb (β-klotho were downregulated in the liver, while Fgfr1 was downregulated in WAT of KD-fed mice. Because inflammation could be one of the mechanisms linking KD to impaired FGF21 signaling, we measured the expression levels of inflammatory markers and macrophage accumulation in WAT and liver and found an increased inflammation and macrophage accumulation in the liver, but surprisingly, a reduction of inflammation in WAT.We also showed that KD enhances lipid accumulation in the liver, which may explain hepatic inflammation and impaired Fgfr4 and Klb expression. In contrast, import of lipids from the circulation was significantly reduced in WAT of KD-fed mice, as suggested by a downregulation of Lpl and Cd36. This was further associated with reduced inflammation in WAT.Altogether, these results indicate that KD could be beneficial for a given tissue but deleterious for another.

  20. Optimization of Contrast-to-Tissue Ratio by Adaptation of Transmitted Ternary Signal in Ultrasound Pulse Inversion Imaging

    Directory of Open Access Journals (Sweden)

    Sébastien Ménigot

    2013-01-01

    Full Text Available Ultrasound contrast imaging has provided more accurate medical diagnoses thanks to the development of innovating modalities like the pulse inversion imaging. However, this latter modality that improves the contrast-to-tissue ratio (CTR is not optimal, since the frequency is manually chosen jointly with the probe. However, an optimal choice of this command is possible, but it requires precise information about the transducer and the medium which can be experimentally difficult to obtain, even inaccessible. It turns out that the optimization can become more complex by taking into account the kind of generators, since the generators of electrical signals in a conventional ultrasound scanner can be unipolar, bipolar, or tripolar. Our aim was to seek the ternary command which maximized the CTR. By combining a genetic algorithm and a closed loop, the system automatically proposed the optimal ternary command. In simulation, the gain compared with the usual ternary signal could reach about 3.9 dB. Another interesting finding was that, in contrast to what is generally accepted, the optimal command was not a fixed-frequency signal but had harmonic components.

  1. Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation

    DEFF Research Database (Denmark)

    Rittig, Nikolaj; Bach, Ermina; Thomsen, Henrik Holm

    2016-01-01

    BACKGROUND: Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α), stress-hormones, and insulin. The intracellular mechanisms remain elusive and we therefore measured pro- and anti-lipolytic signaling pathways...... to measure palmitate rate of appearance (Rapalmitate) and indirect calorimetry was performed to measure energy expenditures and lipid oxidation rates. A subcutaneous abdominal fat biopsy was obtained during both interventions and subjected to western blotting and qPCR quantifications. RESULTS: LPS caused...... a mean increase in serum free fatty acids (FFA) concentrations of 90% (CI-95%: 37-142, p = 0.005), a median increase in Rapalmitate of 117% (CI-95%: 77-166, penergy expenditure of 28% (CI-95%: 16-42, p...

  2. Individual Polychlorinated Biphenyl (PCB) Congeners Produce Tissue- and Gene-Specific Effects on Thyroid Hormone Signaling during Development

    Science.gov (United States)

    Giera, Stefanie; Bansal, Ruby; Ortiz-Toro, Theresa M.; Taub, Daniel G.

    2011-01-01

    Polychlorinated biphenyls (PCB) are industrial chemicals linked to developmental deficits that may be caused in part by disrupting thyroid hormone (TH) action by either reducing serum TH or interacting directly with the TH receptor (TR). Individual PCB congeners can activate the TR in vitro when the metabolic enzyme cytochrome P4501A1 (CYP1A1) is induced, suggesting that specific PCB metabolites act as TR agonists. To test this hypothesis in vivo, we compared two combinations of PCB congeners that either activate the TR (PCB 105 and 118) or not (PCB 138 and 153) in the presence or absence of a PCB congener (PCB 126) that induces CYP1A1 in vitro. Aroclor 1254 was used as a positive control, and a group treated with propylthiouracil was included to characterize the effects of low serum TH. We monitored the effects on TH signaling in several peripheral tissues by measuring the mRNA expression of well-known TH-response genes in these tissues. Aroclor 1254 and its component PCB 105/118/126 reduced total T4 to the same extent as that of propylthiouracil but increased the expression of some TH target genes in liver. This effect was strongly correlated with CYP1A1 expression supporting the hypothesis that metabolism is necessary. Effects were gene and tissue specific, indicating that tissue-specific metabolism is an important component of PCB disruption of TH action and that PCB metabolites interact in complex ways with the TR. These are essential mechanisms to consider when evaluating the health risks of contaminant exposures, for both PCB and other polycyclic compounds known to interact with nuclear hormone receptors. PMID:21540284

  3. Selection and validation of reference genes for quantitative gene expression analyses in various tissues and seeds at different developmental stages in Bixa orellana L.

    Science.gov (United States)

    Moreira, Viviane S; Soares, Virgínia L F; Silva, Raner J S; Sousa, Aurizangela O; Otoni, Wagner C; Costa, Marcio G C

    2018-05-01

    Bixa orellana L., popularly known as annatto, produces several secondary metabolites of pharmaceutical and industrial interest, including bixin, whose molecular basis of biosynthesis remain to be determined. Gene expression analysis by quantitative real-time PCR (qPCR) is an important tool to advance such knowledge. However, correct interpretation of qPCR data requires the use of suitable reference genes in order to reduce experimental variations. In the present study, we have selected four different candidates for reference genes in B. orellana , coding for 40S ribosomal protein S9 (RPS9), histone H4 (H4), 60S ribosomal protein L38 (RPL38) and 18S ribosomal RNA (18SrRNA). Their expression stabilities in different tissues (e.g. flower buds, flowers, leaves and seeds at different developmental stages) were analyzed using five statistical tools (NormFinder, geNorm, BestKeeper, ΔCt method and RefFinder). The results indicated that RPL38 is the most stable gene in different tissues and stages of seed development and 18SrRNA is the most unstable among the analyzed genes. In order to validate the candidate reference genes, we have analyzed the relative expression of a target gene coding for carotenoid cleavage dioxygenase 1 (CCD1) using the stable RPL38 and the least stable gene, 18SrRNA , for normalization of the qPCR data. The results demonstrated significant differences in the interpretation of the CCD1 gene expression data, depending on the reference gene used, reinforcing the importance of the correct selection of reference genes for normalization.

  4. Identification of reference genes for RT-qPCR in ovine mammary tissue during late pregnancy and lactation and in response to maternal nutritional programming.

    Science.gov (United States)

    Paten, A M; Pain, S J; Peterson, S W; Blair, H T; Kenyon, P R; Dearden, P K; Duncan, E J

    2014-08-01

    The mammary gland is a complex tissue consisting of multiple cell types which, over the lifetime of an animal, go through repeated cycles of development associated with pregnancy, lactation and involution. The mammary gland is also known to be sensitive to maternal programming by environmental stimuli such as nutrition. The molecular basis of these adaptations is of significant interest, but requires robust methods to measure gene expression. Reverse-transcription quantitative PCR (RT-qPCR) is commonly used to measure gene expression, and is currently the method of choice for validating genome-wide expression studies. RT-qPCR requires the selection of reference genes that are stably expressed over physiological states and treatments. In this study we identify suitable reference genes to normalize RT-qPCR data for the ovine mammary gland in two physiological states; late pregnancy and lactation. Biopsies were collected from offspring of ewes that had been subjected to different nutritional paradigms during pregnancy to examine effects of maternal programming on the mammary gland of the offspring. We evaluated eight candidate reference genes and found that two reference genes (PRPF3 and CUL1) are required for normalising RT-qPCR data from pooled RNA samples, but five reference genes are required for analyzing gene expression in individual animals (SENP2, EIF6, MRPL39, ATP1A1, CUL1). Using these stable reference genes, we showed that TET1, a key regulator of DNA methylation, is responsive to maternal programming and physiological state. The identification of these novel reference genes will be of utility to future studies of gene expression in the ovine mammary gland. Copyright © 2014 the American Physiological Society.

  5. Regulation of cell behavior and tissue patterning by bioelectrical signals: challenges and opportunities for biomedical engineering.

    Science.gov (United States)

    Levin, Michael; Stevenson, Claire G

    2012-01-01

    Achieving control over cell behavior and pattern formation requires molecular-level understanding of regulatory mechanisms. Alongside transcriptional networks and biochemical gradients, there functions an important system of cellular communication and control: transmembrane voltage gradients (V(mem)). Bioelectrical signals encoded in spatiotemporal changes of V(mem) control cell proliferation, migration, and differentiation. Moreover, endogenous bioelectrical gradients serve as instructive cues mediating anatomical polarity and other organ-level aspects of morphogenesis. In the past decade, significant advances in molecular physiology have enabled the development of new genetic and biophysical tools for the investigation and functional manipulation of bioelectric cues. Recent data implicate V(mem) as a crucial epigenetic regulator of patterning events in embryogenesis, regeneration, and cancer. We review new conceptual and methodological developments in this fascinating field. Bioelectricity offers a novel way of quantitatively understanding regulation of growth and form in vivo, and it reveals tractable, powerful control points that will enable truly transformative applications in bioengineering, regenerative medicine, and synthetic biology.

  6. Assessment of stability of trace elements in two natural matrix environmental standard reference materials. NIST-SRM 1547 Peach leaves and NIST-SRM 1566a Oyster Tissue

    International Nuclear Information System (INIS)

    Mackey, E.A.; Spatz, R.O.

    2009-01-01

    The NIST program for environmental Standard Reference Materials (SRM) includes materials covering a range of matrices, mass fraction values and analytes. For many SRMs, mass fraction data are accumulated, incidentally, over time, as these are used routinely for quality assurance purposes. Although these are not formal stability studies, data generated may be useful in assessing stability. To evaluate the potential for assessing material stability from incidental use of SRMs, results of neutron activation analysis performed from 1992 through 2008 were compiled for SRM 1547 Peach Leaves and SRM 1566a Oyster Tissue. Results indicate that incidental use of SRMs yields useful information on SRM stability. (author)

  7. The radiographic and MRI features of gout referred as suspected soft tissue sarcoma: a review of the literature and findings from 27 cases

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Neil [Imperial College Healthcare NHS Trust, Imaging Department, London (United Kingdom); Saifuddin, Asif [The Royal National Orthopaedic Hospital NHS Trust, Department of Radiology, Stanmore, Middlesex (United Kingdom)

    2014-09-24

    Gout has been termed the ''great mimicker'', for its ability to resemble other pathological conditions. Whilst the typical imaging features of gout are well described, there is a relative paucity of literature describing more challenging cases of gout, where a malignant tumour has been considered in the differential diagnosis. The aim of this article is to provide an overview of the radiographic and MRI features of 27 cases of gout that were initially referred to our centre as suspected soft tissue sarcoma, alongside a review of the literature. (orig.)

  8. The radiographic and MRI features of gout referred as suspected soft tissue sarcoma: a review of the literature and findings from 27 cases

    International Nuclear Information System (INIS)

    Upadhyay, Neil; Saifuddin, Asif

    2015-01-01

    Gout has been termed the ''great mimicker'', for its ability to resemble other pathological conditions. Whilst the typical imaging features of gout are well described, there is a relative paucity of literature describing more challenging cases of gout, where a malignant tumour has been considered in the differential diagnosis. The aim of this article is to provide an overview of the radiographic and MRI features of 27 cases of gout that were initially referred to our centre as suspected soft tissue sarcoma, alongside a review of the literature. (orig.)

  9. Annotation Of Novel And Conserved MicroRNA Genes In The Build 10 Sus scrofa Reference Genome And Determination Of Their Expression Levels In Ten Different Tissues

    DEFF Research Database (Denmark)

    Thomsen, Bo; Nielsen, Mathilde; Hedegaard, Jakob

    The DNA template used in the pig genome sequencing project was provided by a Duroc pig named TJ Tabasco. In an effort to annotate microRNA (miRNA) genes in the reference genome we have conducted deep sequencing to determine the miRNA transcriptomes in ten different tissues isolated from Pinky......, a genetically identical clone of TJ Tabasco. The purpose was to generate miRNA sequences that are highly homologous to the reference genome sequence, which along with computational prediction will improve confidence in the genomic annotation of miRNA genes. Based on homology searches of the sequence data...... against miRBase, we identified more than 600 conserved known miRNA/miRNA*, which is a significant increase relative to the 211 porcine miRNA/miRNA* deposited in the current version of miRBase. Furthermore, the genome-wide transcript profiles provided important information on the relative abundance...

  10. Tissue regeneration and biomineralization in sea urchins: role of Notch signaling and presence of stem cell markers.

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    Helena C Reinardy

    Full Text Available Echinoderms represent a phylum with exceptional regenerative capabilities that can reconstruct both external appendages and internal organs. Mechanistic understanding of the cellular pathways involved in regeneration in these animals has been hampered by the limited genomic tools and limited ability to manipulate regenerative processes. We present a functional assay to investigate mechanisms of tissue regeneration and biomineralization by measuring the regrowth of amputated tube feet (sensory and motor appendages and spines in the sea urchin, Lytechinus variegatus. The ability to manipulate regeneration was demonstrated by concentration-dependent inhibition of regrowth of spines and tube feet by treatment with the mitotic inhibitor, vincristine. Treatment with the gamma-secretase inhibitor DAPT resulted in a concentration-dependent inhibition of regrowth, indicating that both tube feet and spine regeneration require functional Notch signaling. Stem cell markers (Piwi and Vasa were expressed in tube feet and spine tissue, and Vasa-positive cells were localized throughout the epidermis of tube feet by immunohistochemistry, suggesting the existence of multipotent progenitor cells in these highly regenerative appendages. The presence of Vasa protein in other somatic tissues (e.g. esophagus, radial nerve, and a sub-population of coelomocytes suggests that multipotent cells are present throughout adult sea urchins and may contribute to normal homeostasis in addition to regeneration. Mechanistic insight into the cellular pathways governing the tremendous regenerative capacity of echinoderms may reveal processes that can be modulated for regenerative therapies, shed light on the evolution of regeneration, and enable the ability to predict how these processes will respond to changing environmental conditions.

  11. Down-Regulation of AKT Signalling by Ursolic Acid Induces Intrinsic Apoptosis and Sensitization to Doxorubicin in Soft Tissue Sarcoma.

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    Victor Hugo Villar

    Full Text Available Several important biological activities have been attributed to the pentacyclic triterpene ursolic acid (UA, being its antitumoral effect extensively studied in human adenocarcinomas. In this work, we focused on the efficacy and molecular mechanisms involved in the antitumoral effects of UA, as single agent or combined with doxorubicin (DXR, in human soft tissue sarcoma cells. UA (5-50 μM strongly inhibited (up to 80% the viability of STS cells at 24 h and its proliferation in soft agar, with higher concentrations increasing apoptotic death up to 30%. UA treatment (6-9 h strongly blocked the survival AKT/GSK3β/β-catenin signalling pathway, which led to a concomitant reduction of the anti-apoptotic proteins c-Myc and p21, altogether resulting in the activation of intrinsic apoptosis. Interestingly, UA at low concentrations (10-15 μM enhanced the antitumoral effects of DXR by up to 2-fold, while in parallel inhibiting DXR-induced AKT activation and p21 expression, two proteins implicated in antitumoral drug resistance and cell survival. In conclusion, UA is able to induce intrinsic apoptosis in human STS cells and also to sensitize these cells to DXR by blocking the AKT signalling pathway. Therefore, UA may have beneficial effects, if used as nutraceutical adjuvant during standard chemotherapy treatment of STS.

  12. Validation of the reference tissue model for estimation of dopaminergic D{sub 2}-like receptor binding with [{sup 18}F](N-methyl)benperidol in humans

    Energy Technology Data Exchange (ETDEWEB)

    Antenor-Dorsey, Jo Ann V. [Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO (United States); Markham, Joanne; Moerlein, Stephen M. [Department of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Videen, Tom O. [Department of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Department of Neurology, Washington University School of Medicine, St. Louis, MO (United States); Perlmutter, Joel S. [Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO (United States); Department of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Department of Neurology, Washington University School of Medicine, St. Louis, MO (United States); Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO (United States)], E-mail: joel@npg.wustl.edu

    2008-04-15

    Positron emission tomography measurements of dopaminergic D{sub 2}-like receptors may provide important insights into disorders such as Parkinson's disease, schizophrenia, dystonia and Tourette's syndrome. The positron emission tomography (PET) radioligand [{sup 18}F](N-methyl)benperidol ([{sup 18}F]NMB) has high affinity and selectivity for D{sub 2}-like receptors and is not displaced by endogenous dopamine. The goal of this study is to evaluate the use of a graphical method utilizing a reference tissue region for [{sup 18}F]-NMB PET analysis by comparisons to an explicit three-compartment tracer kinetic model and graphical method that use arterial blood measurements. We estimated binding potential (BP) in the caudate and putamen using all three methods in 16 humans and found that the three-compartment tracer kinetic method provided the highest BP estimates while the graphical method using a reference region yielded the lowest estimates (P<.0001 by repeated-measures ANOVA). However, the three methods yielded highly correlated BP estimates for the two regions of interest. We conclude that the graphical method using a reference region still provides a useful estimate of BP comparable to methods using arterial blood sampling, especially since the reference region method is less invasive and computationally more straightforward, thereby simplifying these measurements.

  13. Validation of the reference tissue model for estimation of dopaminergic D2-like receptor binding with [18F](N-methyl)benperidol in humans

    International Nuclear Information System (INIS)

    Antenor-Dorsey, Jo Ann V.; Markham, Joanne; Moerlein, Stephen M.; Videen, Tom O.; Perlmutter, Joel S.

    2008-01-01

    Positron emission tomography measurements of dopaminergic D 2 -like receptors may provide important insights into disorders such as Parkinson's disease, schizophrenia, dystonia and Tourette's syndrome. The positron emission tomography (PET) radioligand [ 18 F](N-methyl)benperidol ([ 18 F]NMB) has high affinity and selectivity for D 2 -like receptors and is not displaced by endogenous dopamine. The goal of this study is to evaluate the use of a graphical method utilizing a reference tissue region for [ 18 F]-NMB PET analysis by comparisons to an explicit three-compartment tracer kinetic model and graphical method that use arterial blood measurements. We estimated binding potential (BP) in the caudate and putamen using all three methods in 16 humans and found that the three-compartment tracer kinetic method provided the highest BP estimates while the graphical method using a reference region yielded the lowest estimates (P<.0001 by repeated-measures ANOVA). However, the three methods yielded highly correlated BP estimates for the two regions of interest. We conclude that the graphical method using a reference region still provides a useful estimate of BP comparable to methods using arterial blood sampling, especially since the reference region method is less invasive and computationally more straightforward, thereby simplifying these measurements

  14. Meaning From Environmental Sounds: Types of Signal-Referent Relations and Their Effect on Recognizing Auditory Icons

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    Keller, Peter; Stevens, Catherine

    2004-01-01

    This article addresses the learnability of auditory icons, that is, environmental sounds that refer either directly or indirectly to meaningful events. Direct relations use the sound made by the target event whereas indirect relations substitute a surrogate for the target. Across 3 experiments, different indirect relations (ecological, in which…

  15. Selection of reference genes for quantitative real-time PCR expression studies of microdissected reproductive tissues in apomictic and sexual Boechera

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    Amiteye Samuel

    2011-08-01

    Full Text Available Abstract Background Apomixis, a natural form of asexual seed production in plants, is considered to have great biotechnological potential for agriculture. It has been hypothesised that de-regulation of the sexual developmental pathway could trigger apomictic reproduction. The genus Boechera represents an interesting model system for understanding apomixis, having both sexual and apomictic genotypes at the diploid level. Quantitative qRT-PCR is the most extensively used method for validating genome-wide gene expression analyses, but in order to obtain reliable results, suitable reference genes are necessary. In this work we have evaluated six potential reference genes isolated from a 454 (FLX derived cDNA library of Boechera. RNA from live microdissected ovules and anthers at different developmental stages, as well as vegetative tissues of apomictic and sexual Boechera, were used to validate the candidates. Results Based on homologies with Arabidopsis, six genes were selected from a 454 cDNA library of Boechera: RPS18 (Ribosomal sub protein 18, Efalpha1 (Elongation factor 1 alpha, ACT 2 (Actin2, UBQ (polyubiquitin, PEX4 (Peroxisomal ubiquitin conjugating enzyme and At1g09770.1 (Arabidopsis thaliana cell division cycle 5. Total RNA was extracted from 17 different tissues, qRT-PCRs were performed, and raw Ct values were analyzed for primer efficiencies and gene ratios. The geNorm and normFinder applications were used for selecting the most stable genes among all tissues and specific tissue groups (ovule, anthers and vegetative tissues in both apomictic and sexual plants separately. Our results show that BoechRPS18, BoechEfα1, BoechACT2 and BoechUBQ were the most stable genes. Based on geNorm, the combinations of BoechRPS18 and BoechEfα1 or BoechUBQ and BoechEfα1 were the most stable in the apomictic plant, while BoechRPS18 and BoechACT2 or BoechUBQ and BoechACT2 performed best in the sexual plant. When subgroups of tissue samples were analyzed

  16. Probucol Attenuates Cyclophosphamide-induced Oxidative Apoptosis, p53 and Bax Signal Expression in Rat Cardiac Tissues

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    Yousif A. Asiri

    2010-01-01

    Full Text Available Cyclophosphamide (CP is a widely used drug in cancer chemotherapy and immunosuppression, which could cause toxicity of the normal cells due to its toxic metabolites. Probucol, a cholesterol-lowering drug, acts as potential inhibitor of DNA damage and shows to protect against doxorubicin-induced cardiomyopathy by enhancing the endogenous antioxidant system including glutathione peroxidase, catalase and superoxide dismutase. This study examined the possible protective effects of probucol, a lipid-lowering compound with strong antioxidant properties, against CPinduced cardiotoxicity. This objective could be achieved through studying the gene expression-based on the possible protective effects of probucol against CP-induced cardiac failure in rats. Adult male Wistar albino rats were assigned into four treatment groups: Animals in the first (control and second (probucol groups were injected intraperitoneally with corn oil and probucol (61 mg/kg/day, respectively, for two weeks. Animals in the third (CP and fourth (probucol plus CP groups were injected with the same doses of corn oil and probucol (61 mg/kg/day, respectively, for one week before and one week after a single dose of CP (200 mg/kg, I.P.. The p53, Bax, Bcl2 and oxidative genes signal expression were measured by real time PCR. CP-induced cardiotoxicity was clearly observed by a significant increase in serum creatine phosphokinase isoenzyme (CK-MB (117%, lactate dehydrogenase (LDH (64%, free (69% and esterified cholesterol (42% and triglyceride (69% compared to control group. In cardiac tissues, CP significantly increases the mRNA expression levels of apoptotic genes, p53 with two-fold and Bax with 1.6-fold, and decreases the anti-apoptotic gene Bcl2 with 0.5-fold. Moreover, CP caused downregulation of antioxidant genes, glutathione peroxidase, catalase, and superoxide dismutase and increased the lipid peroxidation and decreased adenosine triphosphate (ATP (40% and ATP/ADP (44% in cardiac

  17. Food allergens and mucosal immune systems with special reference to recognition of food allergens by gut-associated lymphoid tissue

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    Shuichi Kaminogawa

    1999-01-01

    Full Text Available Food allergy, triggered by an aberrant immune response elicited by orally ingested food allergens, is generated through a complicated mechanism because the allergen interacts with the mucosal immune system (the gut- associated lymphoid tissue, GALT and the resulting immune response affects the generation of allergy. This review will describe the process by which antigens or allergens are recognized by the GALT and the characteristic immune responses induced thereafter. Orally administered antigens induce distinct immune responses in the Peyer's patches, lamina propria and the intestinal epithelium. In addition to these local immune responses in the gut, ingested antigens are known to affect systemic immunity. These may induce a suppressed state of systemic immune responsiveness, which is called oral tolerance, or in some cases they may elicit a systemic IgE antibody response which may lead to allergic reactions. Information on the regions on food allergens recognized by T cells and IgE antibodies is important in understanding the fates of food allergens after being recognized by the GALT. The structure of T and B cell epitopes on food allergens and the possibility of modulation of allergic reactions by amino-acid substituted analogs of allergen- derived peptides will also be discussed.

  18. Effects of nitrogen infiltration into plant tissue on the metabolism of carbon, with special reference to Themeda triandra Forssk

    Energy Technology Data Exchange (ETDEWEB)

    Amory, A M

    1983-01-01

    The infiltration of nitrate and ammonia into Themeda triandra and Zea mays leaf tissue influenced the carbon dioxide gas exchange characteristics: 1) the carbon dioxide compensation point increased, 2) the net photosynthetic rate was increased by the nitrate ion and decreased by the ammonium ion, and 3) dark respiration was unaffected. /sup 14/CO/sub 2/ assimilation and the partitioning of /sup 14/C by Themeda triandra leaves were influenced by the infiltration of both forms of nitrogen; the amino acid fraction changed in both composition and concentration. Nitrogen infiltration increased the activities of the following enzymes: aspartate amino-transferase, PEP carboxylase and RuBP carboxylase. Methionine sulphoximine (inhibitor of glutamate synthetase) increased the carbon dioxide compensation point and formate pool size. Infiltration of nitrate and ammonia enhanced the /sup 14/C uptake from labelled glycolate, glyoxylate and formate into the water soluble fraction of Themeda triandra leaves. The activities of RuBP carboxylase and RuBP oxygenase (to a greater extent) were increased by the addition of nitrate and ammonia in vitro.

  19. Signal-to-noise contribution of principal component loads in reconstructed near-infrared Raman tissue spectra.

    Science.gov (United States)

    Grimbergen, M C M; van Swol, C F P; Kendall, C; Verdaasdonk, R M; Stone, N; Bosch, J L H R

    2010-01-01

    The overall quality of Raman spectra in the near-infrared region, where biological samples are often studied, has benefited from various improvements to optical instrumentation over the past decade. However, obtaining ample spectral quality for analysis is still challenging due to device requirements and short integration times required for (in vivo) clinical applications of Raman spectroscopy. Multivariate analytical methods, such as principal component analysis (PCA) and linear discriminant analysis (LDA), are routinely applied to Raman spectral datasets to develop classification models. Data compression is necessary prior to discriminant analysis to prevent or decrease the degree of over-fitting. The logical threshold for the selection of principal components (PCs) to be used in discriminant analysis is likely to be at a point before the PCs begin to introduce equivalent signal and noise and, hence, include no additional value. Assessment of the signal-to-noise ratio (SNR) at a certain peak or over a specific spectral region will depend on the sample measured. Therefore, the mean SNR over the whole spectral region (SNR(msr)) is determined in the original spectrum as well as for spectra reconstructed from an increasing number of principal components. This paper introduces a method of assessing the influence of signal and noise from individual PC loads and indicates a method of selection of PCs for LDA. To evaluate this method, two data sets with different SNRs were used. The sets were obtained with the same Raman system and the same measurement parameters on bladder tissue collected during white light cystoscopy (set A) and fluorescence-guided cystoscopy (set B). This method shows that the mean SNR over the spectral range in the original Raman spectra of these two data sets is related to the signal and noise contribution of principal component loads. The difference in mean SNR over the spectral range can also be appreciated since fewer principal components can

  20. Quorum sensing signaling molecules produced by reference and emerging soft-rot bacteria (Dickeya and Pectobacterium spp..

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    Alexandre Crépin

    Full Text Available Several small diffusible molecules are involved in bacterial quorum sensing and virulence. The production of autoinducers-1 and -2, quinolone, indole and γ-amino butyrate signaling molecules was investigated in a set of soft-rot bacteria belonging to six Dickeya or Pectobacterium species including recent or emerging potato isolates.Using bacterial biosensors, immunoassay, and chromatographic analysis, we showed that soft-rot bacteria have the common ability to produce transiently during their exponential phase of growth the N-3-oxo-hexanoyl- or the N-3-oxo-octanoyl-l-homoserine lactones and a molecule of the autoinducer-2 family. Dickeya spp. produced in addition the indole-3-acetic acid in tryptophan-rich conditions. All these signaling molecules have been identified for the first time in the novel Dickeya solani species. In contrast, quinolone and γ-amino butyrate signals were not identified and the corresponding synthases are not present in the available genomes of soft-rot bacteria. To determine if the variations of signal production according to growth phase could result from expression modifications of the corresponding synthase gene, the respective mRNA levels were estimated by reverse transcriptase-PCR. While the N-acyl-homoserine lactone production is systematically correlated to the synthase expression, that of the autoinducer-2 follows the expression of an enzyme upstream in the activated methyl cycle and providing its precursor, rather than the expression of its own synthase.Despite sharing the S-adenosylmethionine precursor, no strong link was detected between the production kinetics or metabolic pathways of autoinducers-1 and -2. In contrast, the signaling pathway of autoinducer-2 seems to be switched off by the indole-3-acetic acid pathway under tryptophan control. It therefore appears that the two genera of soft-rot bacteria have similarities but also differences in the mechanisms of communication via the diffusible molecules

  1. Quorum Sensing Signaling Molecules Produced by Reference and Emerging Soft-Rot Bacteria (Dickeya and Pectobacterium spp.)

    Science.gov (United States)

    Crépin, Alexandre; Barbey, Corinne; Beury-Cirou, Amélie; Hélias, Valérie; Taupin, Laure; Reverchon, Sylvie; Nasser, William; Faure, Denis; Dufour, Alain; Orange, Nicole; Feuilloley, Marc; Heurlier, Karin; Burini, Jean-François; Latour, Xavier

    2012-01-01

    Background Several small diffusible molecules are involved in bacterial quorum sensing and virulence. The production of autoinducers-1 and -2, quinolone, indole and γ-amino butyrate signaling molecules was investigated in a set of soft-rot bacteria belonging to six Dickeya or Pectobacterium species including recent or emerging potato isolates. Methodology/Principal Findings Using bacterial biosensors, immunoassay, and chromatographic analysis, we showed that soft-rot bacteria have the common ability to produce transiently during their exponential phase of growth the N-3-oxo-hexanoyl- or the N-3-oxo-octanoyl-l-homoserine lactones and a molecule of the autoinducer-2 family. Dickeya spp. produced in addition the indole-3-acetic acid in tryptophan-rich conditions. All these signaling molecules have been identified for the first time in the novel Dickeya solani species. In contrast, quinolone and γ-amino butyrate signals were not identified and the corresponding synthases are not present in the available genomes of soft-rot bacteria. To determine if the variations of signal production according to growth phase could result from expression modifications of the corresponding synthase gene, the respective mRNA levels were estimated by reverse transcriptase-PCR. While the N-acyl-homoserine lactone production is systematically correlated to the synthase expression, that of the autoinducer-2 follows the expression of an enzyme upstream in the activated methyl cycle and providing its precursor, rather than the expression of its own synthase. Conclusions/Significance Despite sharing the S-adenosylmethionine precursor, no strong link was detected between the production kinetics or metabolic pathways of autoinducers-1 and -2. In contrast, the signaling pathway of autoinducer-2 seems to be switched off by the indole-3-acetic acid pathway under tryptophan control. It therefore appears that the two genera of soft-rot bacteria have similarities but also differences in the

  2. Analyses of Tissue Culture Adaptation of Human Herpesvirus-6A by Whole Genome Deep Sequencing Redefines the Reference Sequence and Identifies Virus Entry Complex Changes.

    Science.gov (United States)

    Tweedy, Joshua G; Escriva, Eric; Topf, Maya; Gompels, Ursula A

    2017-12-31

    Tissue-culture adaptation of viruses can modulate infection. Laboratory passage and bacterial artificial chromosome (BAC)mid cloning of human cytomegalovirus, HCMV, resulted in genomic deletions and rearrangements altering genes encoding the virus entry complex, which affected cellular tropism, virulence, and vaccine development. Here, we analyse these effects on the reference genome for related betaherpesviruses, Roseolovirus, human herpesvirus 6A (HHV-6A) strain U1102. This virus is also naturally "cloned" by germline subtelomeric chromosomal-integration in approximately 1% of human populations, and accurate references are key to understanding pathological relationships between exogenous and endogenous virus. Using whole genome next-generation deep-sequencing Illumina-based methods, we compared the original isolate to tissue-culture passaged and the BACmid-cloned virus. This re-defined the reference genome showing 32 corrections and 5 polymorphisms. Furthermore, minor variant analyses of passaged and BACmid virus identified emerging populations of a further 32 single nucleotide polymorphisms (SNPs) in 10 loci, half non-synonymous indicating cell-culture selection. Analyses of the BAC-virus genome showed deletion of the BAC cassette via loxP recombination removing green fluorescent protein (GFP)-based selection. As shown for HCMV culture effects, select HHV-6A SNPs mapped to genes encoding mediators of virus cellular entry, including virus envelope glycoprotein genes gB and the gH/gL complex. Comparative models suggest stabilisation of the post-fusion conformation. These SNPs are essential to consider in vaccine-design, antimicrobial-resistance, and pathogenesis.

  3. The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.

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    Toshiyuki Fukada

    Full Text Available BACKGROUND: Zinc (Zn is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that mice deficient in Zn transporter Slc39a13/Zip13 show changes in bone, teeth and connective tissue reminiscent of the clinical spectrum of human Ehlers-Danlos syndrome (EDS. The Slc39a13 knockout (Slc39a13-KO mice show defects in the maturation of osteoblasts, chondrocytes, odontoblasts, and fibroblasts. In the corresponding tissues and cells, impairment in bone morphogenic protein (BMP and TGF-beta signaling were observed. Homozygosity for a SLC39A13 loss of function mutation was detected in sibs affected by a unique variant of EDS that recapitulates the phenotype observed in Slc39a13-KO mice. CONCLUSIONS/SIGNIFICANCE: Hence, our results reveal a crucial role of SLC39A13/ZIP13 in connective tissue development at least in part due to its involvement in the BMP/TGF-beta signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-beta signaling and connective tissue dysfunction.

  4. Detection of tissue coagulation by decorrelation of ultrasonic echo signals in cavitation-enhanced high-intensity focused ultrasound treatment.

    Science.gov (United States)

    Yoshizawa, Shin; Matsuura, Keiko; Takagi, Ryo; Yamamoto, Mariko; Umemura, Shin-Ichiro

    2016-01-01

    A noninvasive technique to monitor thermal lesion formation is necessary to ensure the accuracy and safety of high-intensity focused ultrasound (HIFU) treatment. The purpose of this study is to ultrasonically detect the tissue change due to thermal coagulation in the HIFU treatment enhanced by cavitation microbubbles. An ultrasound imaging probe transmitted plane waves at a center frequency of 4.5 MHz. Ultrasonic radio-frequency (RF) echo signals during HIFU exposure at a frequency of 1.2 MHz were acquired. Cross-correlation coefficients were calculated between in-phase and quadrature (IQ) data of two B-mode images with an interval time of 50 and 500 ms for the estimation of the region of cavitation and coagulation, respectively. Pathological examination of the coagulated tissue was also performed to compare with the corresponding ultrasonically detected coagulation region. The distribution of minimum hold cross-correlation coefficient between two sets of IQ data with 50-ms intervals was compared with a pulse inversion (PI) image. The regions with low cross-correlation coefficients approximately corresponded to those with high brightness in the PI image. The regions with low cross-correlation coefficients in 500-ms intervals showed a good agreement with those with significant change in histology. The results show that the regions of coagulation and cavitation could be ultrasonically detected as those with low cross-correlation coefficients between RF frames with certain intervals. This method will contribute to improve the safety and accuracy of the HIFU treatment enhanced by cavitation microbubbles.

  5. Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation: A Human Randomized Crossover Trial.

    Directory of Open Access Journals (Sweden)

    Nikolaj Rittig

    Full Text Available Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α, stress-hormones, and insulin. The intracellular mechanisms remain elusive and we therefore measured pro- and anti-lipolytic signaling pathways in adipocytes after in vivo endotoxin exposure.Eight healthy, lean, male subjects were investigated using a randomized cross over trial with two interventions: i bolus injection of saline (Placebo and ii bolus injection of lipopolysaccharide endotoxin (LPS. A 3H-palmitate tracer was used to measure palmitate rate of appearance (Rapalmitate and indirect calorimetry was performed to measure energy expenditures and lipid oxidation rates. A subcutaneous abdominal fat biopsy was obtained during both interventions and subjected to western blotting and qPCR quantifications.LPS caused a mean increase in serum free fatty acids (FFA concentrations of 90% (CI-95%: 37-142, p = 0.005, a median increase in Rapalmitate of 117% (CI-95%: 77-166, p<0.001, a mean increase in lipid oxidation of 49% (CI-95%: 1-96, p = 0.047, and a median increase in energy expenditure of 28% (CI-95%: 16-42, p = 0.001 compared with Placebo. These effects were associated with increased phosphorylation of hormone sensitive lipase (pHSL at ser650 in adipose tissue (p = 0.03, a trend towards elevated pHSL at ser552 (p = 0.09 and cAMP-dependent protein kinase A (PKA phosphorylation of perilipin 1 (PLIN1 (p = 0.09. Phosphatase and tensin homolog (PTEN also tended to increase (p = 0.08 while phosphorylation of Akt at Thr308 tended to decrease (p = 0.09 during LPS compared with Placebo. There was no difference between protein or mRNA expression of ATGL, G0S2, and CGI-58.LPS stimulated lipolysis in adipose tissue and is associated with increased pHSL and signs of increased PLIN1 phosphorylation combined with a trend toward decreased insulin signaling. The combination of these mechanisms appear to be the driving forces

  6. Using Ambystoma mexicanum (Mexican axolotl) embryos, chemical genetics, and microarray analysis to identify signaling pathways associated with tissue regeneration.

    Science.gov (United States)

    Ponomareva, Larissa V; Athippozhy, Antony; Thorson, Jon S; Voss, S Randal

    2015-12-01

    Amphibian vertebrates are important models in regenerative biology because they present exceptional regenerative capabilities throughout life. However, it takes considerable effort to rear amphibians to juvenile and adult stages for regeneration studies, and the relatively large sizes that frogs and salamanders achieve during development make them difficult to use in chemical screens. Here, we introduce a new tail regeneration model using late stage Mexican axolotl embryos. We show that axolotl embryos completely regenerate amputated tails in 7days before they exhaust their yolk supply and begin to feed. Further, we show that axolotl embryos can be efficiently reared in microtiter plates to achieve moderate throughput screening of soluble chemicals to investigate toxicity and identify molecules that alter regenerative outcome. As proof of principle, we identified integration 1 / wingless (Wnt), transforming growth factor beta (Tgf-β), and fibroblast growth factor (Fgf) pathway antagonists that completely block tail regeneration and additional chemicals that significantly affected tail outgrowth. Furthermore, we used microarray analysis to show that inhibition of Wnt signaling broadly affects transcription of genes associated with Wnt, Fgf, Tgf-β, epidermal growth factor (Egf), Notch, nerve growth factor (Ngf), homeotic gene (Hox), rat sarcoma/mitogen-activated protein kinase (Ras/Mapk), myelocytomatosis viral oncogene (Myc), tumor protein 53 (p53), and retinoic acid (RA) pathways. Punctuated changes in the expression of genes known to regulate vertebrate development were observed; this suggests the tail regeneration transcriptional program is hierarchically structured and temporally ordered. Our study establishes the axolotl as a chemical screening model to investigate signaling pathways associated with tissue regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. High-Resolution Ultrasound-Switchable Fluorescence Imaging in Centimeter-Deep Tissue Phantoms with High Signal-To-Noise Ratio and High Sensitivity via Novel Contrast Agents.

    Science.gov (United States)

    Cheng, Bingbing; Bandi, Venugopal; Wei, Ming-Yuan; Pei, Yanbo; D'Souza, Francis; Nguyen, Kytai T; Hong, Yi; Yuan, Baohong

    2016-01-01

    For many years, investigators have sought after high-resolution fluorescence imaging in centimeter-deep tissue because many interesting in vivo phenomena-such as the presence of immune system cells, tumor angiogenesis, and metastasis-may be located deep in tissue. Previously, we developed a new imaging technique to achieve high spatial resolution in sub-centimeter deep tissue phantoms named continuous-wave ultrasound-switchable fluorescence (CW-USF). The principle is to use a focused ultrasound wave to externally and locally switch on and off the fluorophore emission from a small volume (close to ultrasound focal volume). By making improvements in three aspects of this technique: excellent near-infrared USF contrast agents, a sensitive frequency-domain USF imaging system, and an effective signal processing algorithm, for the first time this study has achieved high spatial resolution (~ 900 μm) in 3-centimeter-deep tissue phantoms with high signal-to-noise ratio (SNR) and high sensitivity (3.4 picomoles of fluorophore in a volume of 68 nanoliters can be detected). We have achieved these results in both tissue-mimic phantoms and porcine muscle tissues. We have also demonstrated multi-color USF to image and distinguish two fluorophores with different wavelengths, which might be very useful for simultaneously imaging of multiple targets and observing their interactions in the future. This work has opened the door for future studies of high-resolution centimeter-deep tissue fluorescence imaging.

  8. Effects of Sleep Deprivation on Phase Synchronization as Assessed by Wavelet Phase Coherence Analysis of Prefrontal Tissue Oxyhemoglobin Signals.

    Science.gov (United States)

    Bu, Lingguo; Zhang, Ming; Li, Jianfeng; Li, Fangyi; Liu, Heshan; Li, Zengyong

    2017-01-01

    To reveal the physiological mechanism of the decline in cognitive function after sleep deprivation, a within-subject study was performed to assess sleep deprivation effects on phase synchronization, as revealed by wavelet phase coherence (WPCO) analysis of prefrontal tissue oxyhemoglobin signals. Twenty subjects (10 male and 10 female, 25.5 ± 3.5 years old) were recruited to participate in two tests: one without sleep deprivation (group A) and the other with 24 h of sleep deprivation (group B). Before the test, each subject underwent a subjective evaluation using visual analog scales. A cognitive task was performed by judging three random numbers. Continuous recordings of the near-infrared spectroscopy (NIRS) signals were obtained from both the left and right prefrontal lobes during rest, task, and post-task periods. The WPCO of cerebral Delta [HbO2] signals were analyzed for these three periods for both groups A and B. Six frequency intervals were defined: I: 0.6-2 Hz (cardiac activity), II: 0.145-0.6 Hz (respiratory activity), III: 0.052-0.145 Hz (myogenic activity), IV: 0.021-0.052 Hz (neurogenic activity), V: 0.0095-0.021 Hz (nitric oxide related endothelial activity) and VI: 0.005-0.0095 Hz (non-nitric oxide related endothelial activity). WPCO in intervals III (F = 5.955, p = 0.02) and V (F = 4.7, p = 0.037) was significantly lower in group B than in group A at rest. During the task period, WPCO in intervals III (F = 5.175, p = 0.029) and IV (F = 4.585, p = 0.039) was significantly lower in group B compared with group A. In the post-task recovery period, the WPCO in interval III (F = 6.125, p = 0.02) was significantly lower in group B compared with group A. Reaction time was significantly prolonged, and the accuracy rate and F1 score both declined after sleep deprivation. The decline in WPCO after sleep deprivation indicates reduced phase synchronization between left and right prefrontal oxyhemoglobin oscillations, which may contribute to the diminished

  9. Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/β-Catenin Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yan Liang

    2017-01-01

    Full Text Available Adipose tissue-derived stromal cells (ADSCs are a high-yield source of pluripotent stem cells for use in cell-based therapies. We explored the effect of andrographolide (ANDRO, one of the ingredients of the medicinal herb extract on the neural differentiation of rat ADSCs and associated molecular mechanisms. We observed that rat ADSCs were small and spindle-shaped and expressed multiple stem cell markers including nestin. They were multipotent as evidenced by adipogenic, osteogenic, chondrogenic, and neural differentiation under appropriate conditions. The proportion of cells exhibiting neural-like morphology was higher, and neurites developed faster in the ANDRO group than in the control group in the same neural differentiation medium. Expression levels of the neural lineage markers MAP2, tau, GFAP, and β-tubulin III were higher in the ANDRO group. ANDRO induced a concentration-dependent increase in Wnt/β-catenin signaling as evidenced by the enhanced expression of nuclear β-catenin and the inhibited form of GSK-3β (pSer9. Thus, this study shows for the first time how by enhancing the neural differentiation of ADSCs we expect that ANDRO pretreatment may increase the efficacy of adult stem cell transplantation in nervous system diseases, but more exploration is needed.

  10. WE-DE-206-01: MRI Signal in Biological Tissues - Proton, Spin, T1, T2, T2*

    Energy Technology Data Exchange (ETDEWEB)

    Gorny, K. [Mayo Clinic (United States)

    2016-06-15

    Magnetic resonance imaging (MRI) has become an essential part of clinical imaging due to its ability to render high soft tissue contrast. Instead of ionizing radiation, MRI use strong magnetic field, radio frequency waves and field gradients to create diagnostic useful images. It can be used to image the anatomy and also functional and physiological activities within the human body. Knowledge of the basic physical principles underlying MRI acquisition is vitally important to successful image production and proper image interpretation. This lecture will give an overview of the spin physics, imaging principle of MRI, the hardware of the MRI scanner, and various pulse sequences and their applications. It aims to provide a conceptual foundation to understand the image formation process of a clinical MRI scanner. Learning Objectives: Understand the origin of the MR signal and contrast from the spin physics level. Understand the main hardware components of a MRI scanner and their purposes Understand steps for MR image formation including spatial encoding and image reconstruction Understand the main kinds of MR pulse sequences and their characteristics.

  11. Activation of the Canonical Wnt/β-Catenin Signalling Pathway is Rare in Canine Malignant Melanoma Tissue and Cell Lines

    Science.gov (United States)

    Chon, E.; Thompson, V.; Schmid, S.; Stein, T. J.

    2012-01-01

    Summary Canine malignant melanoma is a highly aggressive tumour associated with a poor overall survival rate due to both local disease recurrence and its highly metastatic nature. Similar to advanced melanoma in man, canine oral melanoma is poorly responsive to conventional anti-cancer therapies. The lack of sustainable disease control warrants investigation of novel therapies, preferably targeting features specific to the tumour and different from normal cells. The Wnt signalling pathway is known to contribute to melanocytic lineage development in vertebrates and perturbation of the Wnt/β-catenin pathway has been implicated in numerous cancer types. Alterations of the Wnt/β-catenin pathway are suggested to occur in a subset of human melanomas, although the precise role of the Wnt/β-catenin pathway in melanoma is yet to be defined. This study investigates the activation status of the canonical Wnt/β-catenin pathway in canine malignant melanoma and its potential as a therapeutic target for treating this disease. The data indicate canonical Wnt/β-catenin pathway activation is a rare event in canine oral malignant melanoma tissue and canine malignant melanoma cell lines. PMID:22901430

  12. Pan-FGFR inhibition leads to blockade of FGF23 signaling, soft tissue mineralization, and cardiovascular dysfunction.

    Science.gov (United States)

    Yanochko, Gina M; Vitsky, Allison; Heyen, Jonathan R; Hirakawa, Brad; Lam, Justine L; May, Jeff; Nichols, Tim; Sace, Frederick; Trajkovic, Dusko; Blasi, Eileen

    2013-10-01

    The fibroblast growth factor receptors (FGFR) play a major role in angiogenesis and are desirable targets for the development of therapeutics. Groups of Wistar Han rats were dosed orally once daily for 4 days with a small molecule pan-FGFR inhibitor (5mg/kg) or once daily for 6 days with a small molecule MEK inhibitor (3mg/kg). Serum phosphorous and FGF23 levels increased in all rats during the course of the study. Histologically, rats dosed with either drug exhibited multifocal, multiorgan soft tissue mineralization. Expression levels of the sodium phosphate transporter Npt2a and the vitamin D-metabolizing enzymes Cyp24a1 and Cyp27b1 were modulated in kidneys of animals dosed with the pan-FGFR inhibitor. Both inhibitors decreased ERK phosphorylation in the kidneys and inhibited FGF23-induced ERK phosphorylation in vitro in a dose-dependent manner. A separate cardiovascular outcome study was performed to monitor hemodynamics and cardiac structure and function of telemetered rats dosed with either the pan-FGFR inhibitor or MEK inhibitor for 3 days. Both compounds increased blood pressure (~+ 17 mmHg), decreased heart rate (~-75 bpm), and modulated echocardiography parameters. Our data suggest that inhibition of FGFR signaling following administration of either pan-FGFR inhibitor or MEK inhibitor interferes with the FGF23 pathway, predisposing animals to hyperphosphatemia and a tumoral calcinosis-like syndrome in rodents.

  13. The effect of aging of formalin-fixed paraffin-embedded tissues on the in situ hybridization and immunohistochemistry signals in cervical lesions.

    Science.gov (United States)

    Nuovo, Allison J; Garofalo, Michela; Mikhail, Alexandria; Nicol, Alcina F; Vianna-Andrade, Cecilia; Nuovo, Gerard J

    2013-09-01

    Formalin-fixed, paraffin-embedded tissues are widely used in biomedical research but little is known about the effect of the age of the block or unstained slides on the in situ hybridization or immunohistochemistry signal. We compared the in situ-based and immunohistochemistry-based signals for cervical intraepithelial neoplasia samples that ranged from 0 to 15 years of age. There was a progressive and statistically significant decrease in the strength of the p16 signal when comparing tissues prepared from recent unstained slides (0 to 1 y old, mean score of 92%) to those of intermediate age (5 to 7 y old, mean score of 49%) to old unstained slides (cut 13 to 15 y ago, mean score of 10%). Equivalent, progressive, and significant decreases in the intensity of the signals for microRNAs, CD45, and human papillomavirus DNA were seen in tissues stored on slides from 5 to 7 years and 13 to 15 years, respectively. However, the diminution of signal was much less, although still statistically significant, if the sections from the 13- to 15-year-old paraffin blocks were prepared in 2012. The data likely does not represent degradation of the targets as extraction of several microRNA from the old blocks showed no detectable degradation, despite the markedly weakened in situ hybridization signal. It is concluded that in situ-based signal for DNA, microRNAs, and proteins in paraffin-embedded tissues are significantly reduced over time, especially when stored long term on glass slides which, in turn, can lead to a significant underestimation of the amount and presence of the nucleic acid or protein target.

  14. Epithelial control of gut-associated lymphoid tissue formation through p38α-dependent restraint of NF-κB signaling

    Science.gov (United States)

    Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

    2015-01-01

    The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. Here we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a non-cell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. PMID:26792803

  15. Epithelial Control of Gut-Associated Lymphoid Tissue Formation through p38α-Dependent Restraint of NF-κB Signaling.

    Science.gov (United States)

    Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

    2016-03-01

    The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. In this study, we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a noncell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are most likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. Copyright © 2016 by The American Association of Immunologists, Inc.

  16. A SHH-FOXF1-BMP4 signaling axis regulating growth and differentiation of epithelial and mesenchymal tissues in ureter development.

    Directory of Open Access Journals (Sweden)

    Tobias Bohnenpoll

    2017-08-01

    Full Text Available The differentiated cell types of the epithelial and mesenchymal tissue compartments of the mature ureter of the mouse arise in a precise temporal and spatial sequence from uncommitted precursor cells of the distal ureteric bud epithelium and its surrounding mesenchyme. Previous genetic efforts identified a member of the Hedgehog (HH family of secreted proteins, Sonic hedgehog (SHH as a crucial epithelial signal for growth and differentiation of the ureteric mesenchyme. Here, we used conditional loss- and gain-of-function experiments of the unique HH signal transducer Smoothened (SMO to further characterize the cellular functions and unravel the effector genes of HH signaling in ureter development. We showed that HH signaling is not only required for proliferation and SMC differentiation of cells of the inner mesenchymal region but also for survival of cells of the outer mesenchymal region, and for epithelial proliferation and differentiation. We identified the Forkhead transcription factor gene Foxf1 as a target of HH signaling in the ureteric mesenchyme. Expression of a repressor version of FOXF1 in this tissue completely recapitulated the mesenchymal and epithelial proliferation and differentiation defects associated with loss of HH signaling while re-expression of a wildtype version of FOXF1 in the inner mesenchymal layer restored these cellular programs when HH signaling was inhibited. We further showed that expression of Bmp4 in the ureteric mesenchyme depends on HH signaling and Foxf1, and that exogenous BMP4 rescued cell proliferation and epithelial differentiation in ureters with abrogated HH signaling or FOXF1 function. We conclude that SHH uses a FOXF1-BMP4 module to coordinate the cellular programs for ureter elongation and differentiation, and suggest that deregulation of this signaling axis occurs in human congenital anomalies of the kidney and urinary tract (CAKUT.

  17. A SHH-FOXF1-BMP4 signaling axis regulating growth and differentiation of epithelial and mesenchymal tissues in ureter development.

    Science.gov (United States)

    Bohnenpoll, Tobias; Wittern, Anna B; Mamo, Tamrat M; Weiss, Anna-Carina; Rudat, Carsten; Kleppa, Marc-Jens; Schuster-Gossler, Karin; Wojahn, Irina; Lüdtke, Timo H-W; Trowe, Mark-Oliver; Kispert, Andreas

    2017-08-01

    The differentiated cell types of the epithelial and mesenchymal tissue compartments of the mature ureter of the mouse arise in a precise temporal and spatial sequence from uncommitted precursor cells of the distal ureteric bud epithelium and its surrounding mesenchyme. Previous genetic efforts identified a member of the Hedgehog (HH) family of secreted proteins, Sonic hedgehog (SHH) as a crucial epithelial signal for growth and differentiation of the ureteric mesenchyme. Here, we used conditional loss- and gain-of-function experiments of the unique HH signal transducer Smoothened (SMO) to further characterize the cellular functions and unravel the effector genes of HH signaling in ureter development. We showed that HH signaling is not only required for proliferation and SMC differentiation of cells of the inner mesenchymal region but also for survival of cells of the outer mesenchymal region, and for epithelial proliferation and differentiation. We identified the Forkhead transcription factor gene Foxf1 as a target of HH signaling in the ureteric mesenchyme. Expression of a repressor version of FOXF1 in this tissue completely recapitulated the mesenchymal and epithelial proliferation and differentiation defects associated with loss of HH signaling while re-expression of a wildtype version of FOXF1 in the inner mesenchymal layer restored these cellular programs when HH signaling was inhibited. We further showed that expression of Bmp4 in the ureteric mesenchyme depends on HH signaling and Foxf1, and that exogenous BMP4 rescued cell proliferation and epithelial differentiation in ureters with abrogated HH signaling or FOXF1 function. We conclude that SHH uses a FOXF1-BMP4 module to coordinate the cellular programs for ureter elongation and differentiation, and suggest that deregulation of this signaling axis occurs in human congenital anomalies of the kidney and urinary tract (CAKUT).

  18. Rationale for Possible Targeting of Histone Deacetylase Signaling in Cancer Diseases with a Special Reference to Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Mehdi Ouaïssi

    2011-01-01

    Full Text Available There is ongoing interest to identify signaling pathways and genes that play a key role in carcinogenesis and the development of resistance to antitumoral drugs. Given that histone deacetylases (HDACs interact with various partners through complex molecular mechanims leading to the control of gene expression, they have captured the attention of a large number of researchers. As a family of transcriptional corepressors, they have emerged as important regulators of cell differentiation, cell cycle progression, and apoptosis. Several HDAC inhibitors (HDACis have been shown to efficiently protect against the growth of tumor cells in vitro as well as in vivo. The pancreatic cancer which represents one of the most aggressive cancer still suffers from inefficient therapy. Recent data, although using in vitro tumor cell cultures and in vivo chimeric mouse model, have shown that some of the HDACi do express antipancreatic tumor activity. This provides hope that some of the HDACi could be potential efficient anti-pancreatic cancer drugs. The purpose of this review is to analyze some of the current data of HDACi as possible targets of drug development and to provide some insight into the current problems with pancreatic cancer and points of interest for further study of HDACi as potential molecules for pancreatic cancer adjuvant therapy.

  19. Functional and gene network analyses of transcriptional signatures characterizing pre-weaned bovine mammary parenchyma or fat pad uncovered novel inter-tissue signaling networks during development

    Directory of Open Access Journals (Sweden)

    Lewin Harris A

    2010-05-01

    Full Text Available Abstract Background The neonatal bovine mammary fat pad (MFP surrounding the mammary parenchyma (PAR is thought to exert proliferative effects on the PAR through secretion of local modulators of growth induced by systemic hormones. We used bioinformatics to characterize transcriptomics differences between PAR and MFP from ~65 d old Holstein heifers. Data were mined to uncover potential crosstalk through the analyses of signaling molecules preferentially expressed in one tissue relative to the other. Results Over 9,000 differentially expressed genes (DEG; False discovery rate ≤ 0.05 were found of which 1,478 had a ≥1.5-fold difference between PAR and MFP. Within the DEG highly-expressed in PAR vs. MFP (n = 736 we noted significant enrichment of functions related to cell cycle, structural organization, signaling, and DNA/RNA metabolism. Only actin cytoskeletal signaling was significant among canonical pathways. DEG more highly-expressed in MFP vs. PAR (n = 742 belong to lipid metabolism, signaling, cell movement, and immune-related functions. Canonical pathways associated with metabolism and signaling, particularly immune- and metabolism-related were significantly-enriched. Network analysis uncovered a central role of MYC, TP53, and CTNNB1 in controlling expression of DEG highly-expressed in PAR vs. MFP. Similar analysis suggested a central role for PPARG, KLF2, EGR2, and EPAS1 in regulating expression of more highly-expressed DEG in MFP vs. PAR. Gene network analyses revealed putative inter-tissue crosstalk between cytokines and growth factors preferentially expressed in one tissue (e.g., ANGPTL1, SPP1, IL1B in PAR vs. MFP; ADIPOQ, IL13, FGF2, LEP in MFP vs. PAR with DEG preferentially expressed in the other tissue, particularly transcription factors or pathways (e.g., MYC, TP53, and actin cytoskeletal signaling in PAR vs. MFP; PPARG and LXR/RXR Signaling in MFP vs. PAR. Conclusions Functional analyses underscored a reciprocal influence in

  20. Pyrexia in cats: Retrospective analysis of signalment, clinical investigations, diagnosis and influence of prior treatment in 106 referred cases.

    Science.gov (United States)

    Spencer, Sarah E; Knowles, Toby; Ramsey, Ian K; Tasker, Séverine

    2017-11-01

    The main aim of the study was to describe the features and diagnoses of a population of cats referred with pyrexia. Other aims were to report and evaluate the utility of clinical investigations performed, and describe any effect of treatment before referral on temperature at presentation and ability to make a diagnosis. Clinical records of cats with pyrexia (⩾39.2°C) documented at least twice were retrospectively reviewed. Cases were assigned to disease categories (infectious, inflammatory, immune-mediated, neoplastic, miscellaneous and no diagnosis [pyrexia of unknown origin, PUO]) based on diagnosis. The overall value of clinical investigations was assessed by classifying them as 'enabling', 'assisting' or 'no assistance' in achieving each diagnosis. The effect of treatment before referral was assessed for any association with temperature at presentation and ability to make a diagnosis (PUO vs other disease categories). One hundred and six cases were identified. The most common cause of pyrexia was feline infectious peritonitis (22 cats, 20.8%) and the largest disease category was infectious (41/106, 38.7%). Inflammatory conditions were found in 19 (17.9%) cats, neoplasia in 13 (12.3%), miscellaneous causes in 11 (10.4%) and immune-mediated disease in six (5.7%). No diagnosis was reached in 16 (15.0%) cats, often despite extensive diagnostic investigations. Cytology and histopathology most often 'enabled' or 'assisted' in obtaining a diagnosis. Most cats (91, 85.8%) received treatment before referral, with antimicrobial treatment given to 87 (82.1%). Prior treatment before referral was not associated with temperature at presentation nor with success in establishing a diagnosis. This is the first study investigating causes of pyrexia in cats. Infectious diseases were most common and immune-mediated diseases were comparatively rare.

  1. Curcumin inhibits TGF-β1-induced connective tissue growth factor expression through the interruption of Smad2 signaling in human gingival fibroblasts.

    Science.gov (United States)

    Chen, Jung-Tsu; Wang, Chen-Ying; Chen, Min-Huey

    2018-01-13

    Many fibrotic processes are associated with an increased level of transforming growth factor-β1 (TGF-β1). TGF-β1 can increase synthesis of matrix proteins and enhance secretion of protease inhibitors, resulting in matrix accumulation. Connective tissue growth factor (CTGF) is a downstream profibrotic effector of TGF-β1 and is associated with the fibrosis in several human organs. Curcumin has been applied to reduce matrix accumulation in fibrotic diseases. This study was aimed to evaluate whether curcumin could suppress TGF-β1-induced CTGF expression and its related signaling pathway involving in this inhibitory action in primary human gingival fibroblasts. The differences in CTGF expression among three types of gingival overgrowth and normal gingival tissues were assessed by immunohistochemistry. Gingival fibroblast viability in cultured media with different concentrations of curcumin was studied by MTT assay. The effect of curcumin on TGF-β1-induced CTGF expression in primary human gingival fibroblasts was examined by immunoblotting. Moreover, the proteins involved in TGF-β1 signaling pathways including TGF-β1 receptors and Smad2 were also analyzed by immunoblotting. CTGF was highly expressed in fibroblasts, epithelial cells and some of endothelial cells, smooth muscle cells, and inflammatory cells in phenytoin-induced gingival overgrowth tissues rather than in those of hereditary and inflammatory gingival overgrowth tissues. Moreover, CTGF expression in the epithelial and connective tissue layers was higher in phenytoin-induced gingival overgrowth tissues than in normal gingival tissues. Curcumin was nontoxic and could reduce TGF-β1-induced CTGF expression by attenuating the phosphorylation and nuclear translocation of Smad2. Curcumin can suppress TGF-β1-induced CTGF expression through the interruption of Smad2 signaling. Copyright © 2018. Published by Elsevier B.V.

  2. [Influence of kaempferol on TGF-β1/Smads signal path in liver tissue of mice with Schistosoma japonicum infection].

    Science.gov (United States)

    Cai, Wen; Zhao, Lei; Li, Hua-rong; Zhang, Shu-ling

    2014-08-01

    To investigate the influence of kaempferol on transforming growth factor(TGF-β1/Smads signal tiransduction in liver tissue of mice with schistosomiasis liver fibrosis. Forty BALB/c mice were randomly divided into a normal control group (8 mice), a praziquantel group (8 mice ), and 4 praziquantel + kaempferol groups with different kaempferol dosages (5, 10, 15, 20 mg/kg respectively, 6 mice each group). Besides the normal control group, all the mice in the other 5 groups were infected with Schistosoma japonicum. After the infection for 6 weeks, the praziquantel group and the 4 praziquantel + kaempferol groups were treated with praziquantel 500 mg/(kg.d) for 2 d, then the mice in the praziquantel group were drenched with normal saline for 6 weeks, and those in the 4 praziquantel + kaempferol groups were drenched with kaempferol 5, 10, 15, 20 mg/kg respectively for 6 weeks. After the treatment, all the animals were sacrificed by the cervical dislocation method, and the area of egg granuloma and the degree of fibrosis in the livers of the mice were observed by HE and Masson staining. The expressions of TGF-β1, Smad2/3, Smad7 proteins were measured by the immunohistochemical method, and the mRNA levels of the 3 proteins were detected by RT-PCR. Compared with the mice in the praziquantel group, the areas of egg granuloma of the liver of the mice in the 4 praziquantel + kaempferol groups were smaller, and the degrees of the hepatic fibrosis of the mice were lesser, and their expressions of Smad2 and Smad3 at protein and their mRNA levels were significantly lower (all P kaempferol can significantly reduce the degrees of hepatic fibrosis and granuloma caused by schistosome eggs after the praziquantel treatment.

  3. Tumour suppression in skin and other tissues via cross-talk between vitamin D- and p53-signalling

    Directory of Open Access Journals (Sweden)

    Joerg eReichrath

    2014-06-01

    Full Text Available P53 and its family members have been implicated in the direct regulation of the vitamin D receptor (VDR. Vitamin D- and p53-signaling pathways have a significant impact on spontaneous or carcinogen-induced malignant transformation of cells, with VDR and p53 representing important tumour suppressors. VDR and the p53/p63/p73 proteins all function typically as receptors or sensors that turn into transcriptional regulators upon stimulus, with the main difference being that the nuclear VDR is activated as a transcription factor after binding its naturally occurring ligand 1,25-dihydroxyvitamin D with high affinity while the p53 family of transcription factors, mostly in the nucleoplasm, responds to a large number of alterations in cell homeostasis commonly referred to as stress. An increasing body of evidence now convincingly demonstrates a cross-talk between vitamin D- and p53-signaling that occurs at different levels, has genome-wide implications and that should be of high importance for many malignancies, including non-melanoma skin cancer. One interaction involves the ability of p53 to increase skin pigmentation via POMC derivatives including alpha-MSH and ACTH. Pigmentation protects the skin against UV-induced DNA damage and skin carcinogenesis, yet on the other hand reduces cutaneous synthesis of vitamin D. A second level of interaction may be through the ability of 1,25-dihydroxyvitamin D to increase the survival of skin cells after UV irradiation. UV irradiation-surviving cells show significant reductions in thymine dimers in the presence of 1,25-dihydroxyvitamin D that are associated with increased nuclear p53 protein expression, and significantly reduced NO products. A third level of interaction is documented by the ability of vitamin D compounds to regulate the expression of the murine double minute 2 (MDM2 gene in dependence of the presence of wild-type p53. MDM2 has a well established role as a key negative regulator of p53 activity

  4. Disrupted G1 to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

    International Nuclear Information System (INIS)

    Devi, Sachin S.; Mehendale, Harihara M.

    2005-01-01

    Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G 0 to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G 1 to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes

  5. The importance of dietary modulation of cAMP and insulin signaling in adipose tissue and the development of obesity

    DEFF Research Database (Denmark)

    Madsen, Lise; Kristiansen, Karsten

    2010-01-01

    branches of cAMP signaling, the canonical protein kinase A-dependent pathways and the novel exchange protein activated by cAMP (Epac)-dependent pathways, and insulin signaling. We discuss how macronutrients via changes in the balance between insulin- and cAMP-dependent signaling can affect the development...

  6. Looking beyond the genes: the interplay between signaling pathways and mechanics in the shaping and diversification of epithelial tissues

    OpenAIRE

    Urdy, Severine; Goudemand, Nicolas; Pantalacci, Sophie

    2016-01-01

    The core of Evo-Devo lies in the intuition that the way tissues grow during embryonic development, the way they sustain their structure and function throughout lifetime, and the way they evolve are closely linked. Epithelial tissues are ubiquitous in metazoans, covering the gut and internal branched organs, as well as the skin and its derivatives (ie, teeth). Here, we discuss in vitro, in vivo, and in silico studies on epithelial tissues to illustrate the conserved, dynamical, and complex asp...

  7. mRNA-seq analysis of the Gossypium arboreum transcriptome reveals tissue selective signaling in response to water stress during seedling stage.

    Directory of Open Access Journals (Sweden)

    Xueyan Zhang

    Full Text Available The cotton diploid species, Gossypium arboreum, shows important properties of stress tolerance and good genetic stability. In this study, through mRNA-seq, we de novo assembled the unigenes of multiple samples with 3h H(2O, NaCl, or PEG treatments in leaf, stem and root tissues and successfully obtained 123,579 transcripts of G. arboreum, 89,128 of which were with hits through BLAST against known cotton ESTs and draft genome of G. raimondii. About 36,961 transcripts (including 1,958 possible transcription factor members were identified with differential expression under water stresses. Principal component analysis of differential expression levels in multiple samples suggested tissue selective signalling responding to water stresses. Venn diagram analysis showed the specificity and intersection of transcripts' response to NaCl and PEG treatments in different tissues. Self-organized mapping and hierarchical cluster analysis of the data also revealed strong tissue selectivity of transcripts under salt and osmotic stresses. In addition, the enriched gene ontology (GO terms for the selected tissue groups were differed, including some unique enriched GO terms such as photosynthesis and tetrapyrrole binding only in leaf tissues, while the stem-specific genes showed unique GO terms related to plant-type cell wall biogenesis, and root-specific genes showed unique GO terms such as monooxygenase activity. Furthermore, there were multiple hormone cross-talks in response to osmotic and salt stress. In summary, our multidimensional mRNA sequencing revealed tissue selective signalling and hormone crosstalk in response to salt and osmotic stresses in G. arboreum. To our knowledge, this is the first such report of spatial resolution of transcriptome analysis in G. arboreum. Our study will potentially advance understanding of possible transcriptional networks associated with water stress in cotton and other crop species.

  8. Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57Bl/6 mice

    NARCIS (Netherlands)

    Duval, C.; Thissen, U.; Keshtkar, S.; Accart, B.; Stienstra, R.; Boekschoten, M.V.; Roskams, T.; Kersten, S.; Müller, M.

    2010-01-01

    OBJECTIVE - Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here, we aimed to investigate the interaction between adipose tissue and liver in NAFLD and identify potential early plasma markers

  9. Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57BL/6 mice.

    NARCIS (Netherlands)

    Duval, C.; Thissen, U.; Keshtkar, S.; Accart, B.; Stienstra, R.; Boekschoten, M.V.; Roskams, T.; Kersten, S.; Muller, M.

    2010-01-01

    OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here, we aimed to investigate the interaction between adipose tissue and liver in NAFLD and identify potential early plasma markers that

  10. Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57Bl/6 mice

    NARCIS (Netherlands)

    Duval, C.N.C.; Thissen, Uwe; Keshtkar, Shohreh; Accard, Bertrand; Stienstra, Rinke; Boekschoten, Mark; Roskams, Tania; Kersten, Sander; Muller, Michael

    2010-01-01

    Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that

  11. Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57BL/6 mice

    NARCIS (Netherlands)

    Duval, C.N.C.; Thissen, U.; Keshtkar, S.; Accart, B.; Stienstra, R.; Boekschoten, M.V.; Roskams, T.; Kersten, A.H.; Müller, M.R.

    2010-01-01

    Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that

  12. GH signaling in human adipose and muscle tissue during 'feast and famine': amplification of exercise stimulation following fasting compared to glucose administration.

    Science.gov (United States)

    Vendelbo, Mikkel H; Christensen, Britt; Grønbæk, Solbritt B; Høgild, Morten; Madsen, Michael; Pedersen, Steen B; Jørgensen, Jens O L; Jessen, Niels; Møller, Niels

    2015-09-01

    Fasting and exercise stimulates, whereas glucose suppresses GH secretion, but it is uncertain how these conditions impact GH signaling in peripheral tissues. To test the original 'feast and famine hypothesis' by Rabinowitz and Zierler, according to which the metabolic effects of GH are predominant during fasting, we specifically hypothesized that fasting and exercise act in synergy to increase STAT-5b target gene expression. Eight healthy men were studied on two occasions in relation to a 1 h exercise bout: i) with a concomitant i.v. glucose infusion ('feast') and ii) after a 36 h fast ('famine'). Muscle and fat biopsy specimens were obtained before, immediately after, and 30 min after exercise. GH increased during exercise on both examination days and this effect was amplified by fasting, and free fatty acid (FFA) levels increased after fasting. STAT-5b phosphorylation increased similarly following exercise on both occasions. In adipose tissue, suppressors of cytokine signaling 1 (SOCS1) and SOCS2 were increased after exercise on the fasting day and both fasting and exercise increased cytokine inducible SH2-containing protein (CISH). In muscle, SOCS2 and CISH mRNA were persistently increased after fasting. Muscle SOCS1, SOCS3, and CISH mRNA expression increased, whereas SOCS2 decreased after exercise on both examination days. This study demonstrates that fasting and exercise act in tandem to amplify STAT-5b target gene expression (SOCS and CISH) in adipose and muscle tissue in accordance with the 'feast and famine hypothesis'; the adipose tissue signaling responses, which hitherto have not been scrutinized, may play a particular role in promoting FFA mobilization. © 2015 European Society of Endocrinology.

  13. Lysophosphatidic acid signaling through its receptor initiates profibrotic epithelial cell fibroblast communication mediated by epithelial cell derived connective tissue growth factor.

    Science.gov (United States)

    Sakai, Norihiko; Chun, Jerold; Duffield, Jeremy S; Lagares, David; Wada, Takashi; Luster, Andrew D; Tager, Andrew M

    2017-03-01

    The expansion of the fibroblast pool is a critical step in organ fibrosis, but the mechanisms driving expansion remain to be fully clarified. We previously showed that lysophosphatidic acid (LPA) signaling through its receptor LPA 1 expressed on fibroblasts directly induces the recruitment of these cells. Here we tested whether LPA-LPA 1 signaling drives fibroblast proliferation and activation during the development of renal fibrosis. LPA 1 -deficient (LPA 1 -/- ) or -sufficient (LPA 1 +/+ ) mice were crossed to mice with green fluorescent protein expression (GFP) driven by the type I procollagen promoter (Col-GFP) to identify fibroblasts. Unilateral ureteral obstruction-induced increases in renal collagen were significantly, though not completely, attenuated in LPA 1 -/- Col-GFP mice, as were the accumulations of both fibroblasts and myofibroblasts. Connective tissue growth factor was detected mainly in tubular epithelial cells, and its levels were suppressed in LPA 1 -/- Col-GFP mice. LPA-LPA 1 signaling directly induced connective tissue growth factor expression in primary proximal tubular epithelial cells, through a myocardin-related transcription factor-serum response factor pathway. Proximal tubular epithelial cell-derived connective tissue growth factor mediated renal fibroblast proliferation and myofibroblast differentiation. Administration of an inhibitor of myocardin-related transcription factor/serum response factor suppressed obstruction-induced renal fibrosis. Thus, targeting LPA-LPA 1 signaling and/or myocardin-related transcription factor/serum response factor-induced transcription could be promising therapeutic strategies for renal fibrosis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  14. Enhanced Inflammation without Impairment of Insulin Signaling in the Visceral Adipose Tissue of 5α-Dihydrotestosterone-Induced Animal Model of Polycystic Ovary Syndrome.

    Science.gov (United States)

    Milutinović, Danijela Vojnović; Nikolić, Marina; Veličković, Nataša; Djordjevic, Ana; Bursać, Biljana; Nestorov, Jelena; Teofilović, Ana; Antić, Ivana Božić; Macut, Jelica Bjekić; Zidane, Abdulbaset Shirif; Matić, Gordana; Macut, Djuro

    2017-09-01

    Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome.Female Wistar rats were treated with nonaromatizable 5α-dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α-dihydrotestosterone-treated animals only at the systemic and not at the level of visceral adipose tissue.The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Evaluation of the role of the cyclooxygenase signaling pathway during inflammation in skin and muscle tissues of ball pythons (Python regius).

    Science.gov (United States)

    Sadler, Ryan A; Schumacher, Juergen P; Rathore, Kusum; Newkirk, Kim M; Cole, Grayson; Seibert, Rachel; Cekanova, Maria

    2016-05-01

    OBJECTIVE To determine degrees of production of cyclooxygenase (COX)-1 and -2 and other mediators of inflammation in noninflamed and inflamed skin and muscle tissues in ball pythons (Python regius). ANIMALS 6 healthy adult male ball pythons. PROCEDURES Biopsy specimens of noninflamed skin and muscle tissue were collected from anesthetized snakes on day 0. A 2-cm skin and muscle incision was then made 5 cm distal to the biopsy sites with a CO2 laser to induce inflammation. On day 7, biopsy specimens of skin and muscle tissues were collected from the incision sites. Inflamed and noninflamed tissue specimens were evaluated for production of COX-1, COX-2, phosphorylated protein kinase B (AKT), total AKT, nuclear factor κ-light-chain-enhancer of activated B cells, phosphorylated extracellular receptor kinases (ERKs) 1 and 2, and total ERK proteins by western blot analysis. Histologic evaluation was performed on H&E-stained tissue sections. RESULTS All biopsy specimens of inflamed skin and muscle tissues had higher histologic inflammation scores than did specimens of noninflamed tissue. Inflamed skin specimens had significantly greater production of COX-1 and phosphorylated ERK than did noninflamed skin specimens. Inflamed muscle specimens had significantly greater production of phosphorylated ERK and phosphorylated AKT, significantly lower production of COX-1, and no difference in production of COX-2, compared with production in noninflamed muscle specimens. CONCLUSIONS AND CLINICAL RELEVANCE Production of COX-1, but not COX-2, was significantly greater in inflamed versus noninflamed skin specimens from ball pythons. Additional research into the reptilian COX signaling pathway is warranted.

  16. Accurate determination of brain metabolite concentrations using ERETIC as external reference.

    Science.gov (United States)

    Zoelch, Niklaus; Hock, Andreas; Heinzer-Schweizer, Susanne; Avdievitch, Nikolai; Henning, Anke

    2017-08-01

    Magnetic Resonance Spectroscopy (MRS) can provide in vivo metabolite concentrations in standard concentration units if a reliable reference signal is available. For 1 H MRS in the human brain, typically the signal from the tissue water is used as the (internal) reference signal. However, a concentration determination based on the tissue water signal most often requires a reliable estimate of the water concentration present in the investigated tissue. Especially in clinically interesting cases, this estimation might be difficult. To avoid assumptions about the water in the investigated tissue, the Electric REference To access In vivo Concentrations (ERETIC) method has been proposed. In this approach, the metabolite signal is compared with a reference signal acquired in a phantom and potential coil-loading differences are corrected using a synthetic reference signal. The aim of this study, conducted with a transceiver quadrature head coil, was to increase the accuracy of the ERETIC method by correcting the influence of spatial B 1 inhomogeneities and to simplify the quantification with ERETIC by incorporating an automatic phase correction for the ERETIC signal. Transmit field ( B1+) differences are minimized with a volume-selective power optimization, whereas reception sensitivity changes are corrected using contrast-minimized images of the brain and by adapting the voxel location in the phantom measurement closely to the position measured in vivo. By applying the proposed B 1 correction scheme, the mean metabolite concentrations determined with ERETIC in 21 healthy subjects at three different positions agree with concentrations derived with the tissue water signal as reference. In addition, brain water concentrations determined with ERETIC were in agreement with estimations derived using tissue segmentation and literature values for relative water densities. Based on the results, the ERETIC method presented here is a valid tool to derive in vivo metabolite

  17. Study on the relationship between PI3K/AKT signaling pathway and apoptosis in cartilage tissue of rats with osteoarthritis

    Directory of Open Access Journals (Sweden)

    Xiao-Yan Li

    2017-05-01

    Full Text Available Objective: To study the relationship between PI3K/AKT signaling pathway and apoptosis in cartilage tissue of rats with osteoarthritis (OA. Methods: The clean male Wistar rats were selected as experimental animals and randomly divided into OA model group and control group. The OA model was established by intra-articular injection of papain solution and L-cysteine. Fourth weeks and eighth weeks after model establishment, the expression of PI3K/AKT signaling molecules, inflammatory mediators, apoptosis marker molecules and autophagy marker molecules in articular cartilage were determined. Results: p-PI3K and p-AKT expression in articular cartilage of OA group were significantly lower than those of control group; IL-1β, IL-6, IL-17, IL-18, eIF4E, Bax, Caspase-3, mTOR, Beclin1, Atg5 and Atg7 expression in articular cartilage of OA group were significantly higher than those of control group and negatively correlated with p-PI3K and p-AKT expression while Bcl-2 expression in articular cartilage of OA group was significantly lower than that of control group and positively correlated with p-PI3K and p-AKT expression. Conclusion: The inhibition of PI3K/AKT signaling pathway in cartilage tissue of OA rat model can promote chondrocyte apoptosis and autophagy.

  18. The sesquiterpene botrydial produced by Botrytis cinerea induces the hypersensitive response on plant tissues and its action is modulated by salicylic acid and jasmonic acid signaling.

    Science.gov (United States)

    Rossi, Franco Rubén; Gárriz, Andrés; Marina, María; Romero, Fernando Matías; Gonzalez, María Elisa; Collado, Isidro González; Pieckenstain, Fernando Luis

    2011-08-01

    Botrytis cinerea, as a necrotrophic fungus, kills host tissues and feeds on the remains. This fungus is able to induce the hypersensitive response (HR) on its hosts, thus taking advantage on the host's defense machinery for generating necrotic tissues. However, the identity of HR effectors produced by B. cinerea is not clear. The aim of this work was to determine whether botrydial, a phytotoxic sesquiterpene produced by B. cinerea, is able to induce the HR on plant hosts, using Arabidopsis thaliana as a model. Botrydial induced the expression of the HR marker HSR3, callose deposition, and the accumulation of reactive oxygen species and phenolic compounds. Botrydial also induced the expression of PR1 and PDF1.2, two pathogenesis-related proteins involved in defense responses regulated by salicylic acid (SA) and jasmonic acid (JA), respectively. A. thaliana and tobacco plants defective in SA signaling were more resistant to botrydial than wild-type plants, as opposed to A. thaliana plants defective in JA signaling, which were more sensitive. It can be concluded that botrydial induces the HR on its hosts and its effects are modulated by host signaling pathways mediated by SA and JA.

  19. Evaluation of the signal-to-noise ratio (SNR) in a CR system and establishment of RQR-M and RQA-M IEC reference radiations in mammography

    International Nuclear Information System (INIS)

    Rosado, Paulo H.G.; Nogueira, Maria S.; Dantas, Marcelino V.A.; Santana, Priscila do C.

    2009-01-01

    In this work, the radiation condition RQR-M e RQA-M of IEC were established in the Siemens Mammomat 3000 mammography equipment. The standard radiation condition are described in terms of: emitting target of molybdenum, percentage ripple not more that 4%, total filtration of 0,032 ± 0,002 mm of molybdenum and specific values of first half-value layer. The results show that the values of parameters were in the range that the IEC recommends. Only the RQAM-3 the value of CSR was not in agreement of the value recommend, and was necessary a additions of 0,1 mm Al in the x-ray tube. After this, the signal noise ratio (SNR) of de Computer radiography (CR) system was evaluated in the reference qualities of RQR-M e RQA-M. For SNR the RQR-M mode of exposure was done with both the 20 mAs and automatic one. To RQA-M the exposure was done with 100 mAs. The variations of the values of SNR were approximated 4%. The tests were done with CR model CR850 made from Kodak and 40 mm of PMMA. (author)

  20. GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus

    DEFF Research Database (Denmark)

    Jørgensen, Jens O L; Jessen, Niels; Pedersen, Steen Bønløkke

    2006-01-01

    Growth hormone (GH) regulates muscle and fat metabolism, which impacts on body composition and insulin sensitivity, but the underlying GH signaling pathways have not been studied in vivo in humans. We investigated GH signaling in biopsies from muscle and abdominal fat obtained 30 (n = 3) or 60 (n...... was measured by in vitro phosphorylation of PI. STAT5 DNA binding activity was assessed with EMSA, and the expression of IGF-I and SOCS mRNA was measured by real-time RT-PCR. GH induced a 52% increase in circulating FFA levels with peak values after 155 min (P = 0.03). Tyrosine-phosphorylated STAT5...... tended to increase after GH in muscle and fat, respectively. We conclude that 1) STAT5 is acutely activated in human muscle and fat after a GH bolus, but additional downstream GH signaling was significant only in fat; 2) the direct GH effects in muscle need further characterization; and 3) this human...

  1. Central GLP-1 receptor signalling accelerates plasma clearance of triacylglycerol and glucose by activating brown adipose tissue in mice

    NARCIS (Netherlands)

    Kooijman, Sander; Wang, Yanan; Parlevliet, Edwin T.; Boon, Mariëtte R.; Edelschaap, David; Snaterse, Gido; Pijl, Hanno; Romijn, Johannes A.; Rensen, Patrick C. N.

    2015-01-01

    Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism, used in the treatment of type 2 diabetes, has recently been shown to increase thermogenesis via the brain. As brown adipose tissue (BAT) produces heat by burning triacylglycerol (TG) and takes up glucose for de novo lipogenesis, the aim of

  2. New Nordic Diet induced weight loss is accompanied by changes in metabolism and AMPK signalling in adipose tissue

    DEFF Research Database (Denmark)

    Fritzen, Andreas Mæchel; Lundsgaard, Annemarie; Jordy, Andreas Børsting

    2015-01-01

    adipose tissue (SCAT) were obtained at week 0 and 26. OUTCOME: Gene and protein expressions were analysed by real time PCR and western blotting. RESULTS: Improved HOMA-IR index and lowered plasma triacylglycerol concentration after NND coincided with molecular adaptations in SCAT, but not in skeletal...

  3. Insulin signaling, inflammation, and lipolysis in subcutaneous adipose tissue of transition dairy cows either overfed energy during the prepartum period or fed a controlled-energy diet.

    Science.gov (United States)

    Mann, S; Nydam, D V; Abuelo, A; Leal Yepes, F A; Overton, T R; Wakshlag, J J

    2016-08-01

    Adipose tissue mobilization is a hallmark of the transition period in dairy cows. Cows overfed energy during the dry period have higher concentrations of nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHB) compared with cows fed a controlled-energy diet prepartum. The reason for an increase in blood NEFA concentrations at the level of adipose tissue in cows overfed energy has not been fully elucidated. One hypothesis is that cows with high BHB concentrations suffer from adipose tissue-specific insulin resistance, leading to higher rates of adipose tissue mobilization in the postpartum period. To test this hypothesis, subcutaneous adipose tissue biopsies of cows overfed energy in excess of predicted requirements by 50% in the dry period, and that had high concentrations of blood BHB postpartum (group H; n=12), were used. Findings were compared with results of biopsies from cows fed a controlled-energy diet and with low BHB concentrations postpartum (group C; n=12) to create the biggest contrast in BHB concentrations. Subcutaneous adipose tissue biopsies were obtained before and 60 min after an intravenous glucose challenge (0.25 g/kg of glucose) at 28 and 10 d before expected calving as well as on d 4 and 21 postpartum. Phosphorylation of protein kinase B, extracellular signal-regulated kinase, and hormone-sensitive lipase was determined before and after glucose infusion by Western blot. Western blot was also used to assess the baseline protein abundance of peroxisome proliferator-activated receptor gamma and insulin receptor β-subunit. In addition, gene expression of fatty acid synthase, adiponectin, monocyte chemoattractant protein 1, and tumor necrosis factor α was determined by real-time quantitative reverse-transcription PCR. Backfat thickness was determined in the thurl area by ultrasonography. Cows in group H showed a greater degree of lipogenesis prepartum, but no differences were found in lipolytic enzyme activity postpartum compared with cows

  4. Impact of tissue atrophy on high-pass filtered MRI signal phase-based assessment in large-scale group-comparison studies: A simulation study

    Science.gov (United States)

    Schweser, Ferdinand; Dwyer, Michael G.; Deistung, Andreas; Reichenbach, Jürgen R.; Zivadinov, Robert

    2013-10-01

    The assessment of abnormal accumulation of tissue iron in the basal ganglia nuclei and in white matter plaques using the gradient echo magnetic resonance signal phase has become a research focus in many neurodegenerative diseases such as multiple sclerosis or Parkinson’s disease. A common and natural approach is to calculate the mean high-pass-filtered phase of previously delineated brain structures. Unfortunately, the interpretation of such an analysis requires caution: in this paper we demonstrate that regional gray matter atrophy, which is concomitant with many neurodegenerative diseases, may itself directly result in a phase shift seemingly indicative of increased iron concentration even without any real change in the tissue iron concentration. Although this effect is relatively small results of large-scale group comparisons may be driven by anatomical changes rather than by changes of the iron concentration.

  5. Dealing with the problem of non-specific in situ mRNA hybridization signals associated with plant tissues undergoing programmed cell death

    Directory of Open Access Journals (Sweden)

    Jokela Anne

    2010-02-01

    Full Text Available Abstract Background In situ hybridization is a general molecular method typically used for the localization of mRNA transcripts in plants. The method provides a valuable tool to unravel the connection between gene expression and anatomy, especially in species such as pines which show large genome size and shortage of sequence information. Results In the present study, expression of the catalase gene (CAT related to the scavenging of reactive oxygen species (ROS and the polyamine metabolism related genes, diamine oxidase (DAO and arginine decarboxylase (ADC, were localized in developing Scots pine (Pinus sylvestris L. seeds. In addition to specific signals from target mRNAs, the probes continually hybridized non-specifically in the embryo surrounding region (ESR of the megagametophyte tissue, in the remnants of the degenerated suspensors as well as in the cells of the nucellar layers, i.e. tissues exposed to cell death processes and extensive nucleic acid fragmentation during Scots pine seed development. Conclusions In plants, cell death is an integral part of both development and defence, and hence it is a common phenomenon in all stages of the life cycle. Our results suggest that extensive nucleic acid fragmentation during cell death processes can be a considerable source of non-specific signals in traditional in situ mRNA hybridization. Thus, the visualization of potential nucleic acid fragmentation simultaneously with the in situ mRNA hybridization assay may be necessary to ensure the correct interpretation of the signals in the case of non-specific hybridization of probes in plant tissues.

  6. Evaluation of light scattering properties and chromophore concentrations in skin tissue based on diffuse reflectance signals at isosbestic wavelengths of hemoglobin

    Science.gov (United States)

    Yokokawa, Takumi; Nishidate, Izumi

    2016-04-01

    We investigate a method to evaluate light-scattering properties and chromophore concentrations in human skin tissue through diffuse reflectance spectroscopy using the reflectance signals acquired at isosbestic wavelengths of hemoglobin (420, 450, 500, and 585 nm). In the proposed method, Monte Carlo simulation-based empirical formulas are used to specify the scattering parameters of skin tissue, such as the scattering amplitude a and the scattering power b, as well as the concentration of melanin C m and the total blood concentration C tb. The use of isosbestic wavelengths of hemoglobin enables the values of C m, C tb, a, and b to be estimated independently of the oxygenation of hemoglobin. The spectrum of the reduced scattering coefficient is reconstructed from the scattering parameters. Experiments using in vivo human skin tissues were performed to confirm the feasibility of the proposed method for evaluating the changes in scattering properties and chromophore concentrations in skin tissue. The experimental results revealed that light scattering is significantly reduced by the application of a glycerol solution, which indicates an optical clearing effect due to osmotic dehydration and the matching of the refractive indices of scatterers in the epidermis.

  7. Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated Aneurysmal Growth Through Disturbed Downstream TGF-β Signaling

    Directory of Open Access Journals (Sweden)

    I. van der Pluijm, PhD

    2016-10-01

    Smad3 deficiency leads to imbalanced activation of downstream genes, no activation of MMPs in VSMCs, and immune responses resulting in rapid aortic wall dilatation and rupture. Our findings uncover new possibilities for treatment of SMAD3 patients; instead of targeting TGF-β signaling, immune suppression may be more beneficial.

  8. Chikusetsu saponin IVa ameliorates high fat diet-induced inflammation in adipose tissue of mice through inhibition of NLRP3 inflammasome activation and NF-κB signaling.

    Science.gov (United States)

    Yuan, Chengfu; Liu, Chaoqi; Wang, Ting; He, Yumin; Zhou, Zhiyong; Dun, Yaoyan; Zhao, Haixia; Ren, Dongming; Wang, Junjie; Zhang, Changcheng; Yuan, Ding

    2017-05-09

    Chronic metabolic inflammation in adipose tissue plays an important role in the development of obesity-associated diseases. Our previous study indicated that total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one main component of SPJ, could exert the anti-oxidative and anti-inflammatory effects. The present study aimed to investigate the in vivo and Ex vivo anti-inflammatory activities of another main component of SPJ, namely Chikusetsu saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis, and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA expression levels of inflammation-related genes and secretion of the chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages (ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced expression of NLRP3 inflammasome component genes and decreased IL-1β and Caspase-1 production in mice. Moreover, CS treatment also inhibited the activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs). Meanwhile, CS treatment inhibited an NLRP3-induced ASC pyroptosome formation and lipopolysaccharide (LPS)-induced pyroptosis. Furthermore, CS treatment suppressed HFD-induced NF-κB signaling in vivo and LPS-induced NF-κB activation as reflected by the fact that their phosphorylated forms and the ratios of pNF-κB/NF-κB, pIKK/IKK, and pIκB/IκB were all decreased in EAT from HFD-fed mice treated with CS as compared with those of HFD mice. Taking together, this study has revealed that CS effectively inhibits HFD-induced inflammation in adipose tissue of mice through inhibiting both NLRP3 inflammasome activation and NF-κB signaling. Thus, CS can serve as a potential therapeutic drug in the prevention and treatment of inflammation-associated diseases.

  9. Trans-10, cis 12-Conjugated Linoleic Acid-Induced Milk Fat Depression Is Associated with Inhibition of PPARγ Signaling and Inflammation in Murine Mammary Tissue

    Directory of Open Access Journals (Sweden)

    Anil K. G. Kadegowda

    2013-01-01

    Full Text Available Exogenous trans-10, cis-12-CLA (CLA reduces lipid synthesis in murine adipose and mammary (MG tissues. However, genomewide alterations in MG and liver (LIV associated with dietary CLA during lactation remain unknown. We fed mice (n=5/diet control or control + trans-10, cis-12-CLA (37 mg/day between d 6 and d 10 postpartum. The 35,302 annotated murine exonic evidence-based oligo (MEEBO microarray and quantitative RT-PCR were used for transcript profiling. Milk fat concentration was 44% lower on d 10 versus d 6 due to CLA. The CLA diet resulted in differential expression of 1,496 genes. Bioinformatics analyses underscored that a major effect of CLA on MG encompassed alterations in cellular signaling pathways and phospholipid species biosynthesis. Dietary CLA induced genes related to ER stress (Xbp1, apoptosis (Bcl2, and inflammation (Orm1, Saa2, and Cp. It also induced marked inhibition of PPARγ signaling, including downregulation of Pparg and Srebf1 and several lipogenic target genes (Scd, Fasn, and Gpam. In LIV, CLA induced hepatic steatosis probably through perturbations in the mitochondrial functions and induction of ER stress. Overall, results from this study underscored the role of PPARγ signaling on mammary lipogenic target regulation. The proinflammatory effect due to CLA could be related to inhibition of PPARγ signaling.

  10. Modeling the relative impact of capsular tissue effects on implanted glucose sensor time lag and signal attenuation.

    Science.gov (United States)

    Novak, Matthew T; Yuan, Fan; Reichert, William M

    2010-10-01

    Little is known mechanistically about why implanted glucose sensors lag behind blood glucose levels in both the time to peak sensor response and the magnitude of peak sensor response. A mathematical model of glucose transport from capillaries through surrounding tissue to the sensor surface was constructed to address how different aspects of the tissue affect glucose transport to an implanted sensor. Physiologically relevant values of capsule diffusion coefficient, capsule porosity, cellular glucose consumption, capsule thickness, and subcutaneous vessel density were used as inputs to create simulated sensor traces that mimic experimental instances of time lag and concentration attenuation relative to a given blood glucose profile. Using logarithmic sensitivity analysis, each parameter was analyzed to study the effect of these variables on both lag and attenuation. Results identify capsule thickness as the strongest determinant of sensor time lag, while subcutaneous vessel density and capsule porosity had the largest effects on attenuation of glucose that reaches the sensor surface. These findings provide mechanistic insight for the rational design of sensor modifications that may alleviate the deleterious consequences of tissue effects on implanted sensor performance.

  11. Activation status of Wnt/ß-catenin signaling in normal and neoplastic breast tissues: relationship to HER2/neu expression in human and mouse.

    Directory of Open Access Journals (Sweden)

    Sara Khalil

    Full Text Available Wnt/ß-catenin signaling is strongly implicated in neoplasia, but the role of this pathway in human breast cancer has been controversial. Here, we examined Wnt/ß-catenin pathway activation as a function of breast cancer progression, and tested for a relationship with HER2/neu expression, using a human tissue microarray comprising benign breast tissues, ductal carcinoma in situ (DCIS, and invasive carcinomas. Cores were scored for membranous ß-catenin, a key functional component of adherens junctions, and for nucleocytoplasmic ß-catenin, a hallmark of Wnt/ß-catenin pathway activation. Only 82% of benign samples exhibited membrane-associated ß-catenin, indicating a finite frequency of false-negative staining. The frequency of membrane positivity was similar in DCIS samples, but was significantly reduced in carcinomas (45%, P<0.001, consistent with loss of adherens junctions during acquisition of invasiveness. Negative membrane status in cancers correlated with higher grade (P = 0.04 and estrogen receptor-negative status (P = 0.03, both indices of poor prognosis. Unexpectedly, a substantial frequency of nucleocytoplasmic ß-catenin was observed in benign breast tissues (36%, similar to that in carcinomas (35%. Positive-staining basal nuclei observed in benign breast may identify putative stem cells. An increased frequency of nucleocytoplasmic ß-catenin was observed in DCIS tumors (56%, suggesting that pathway activation may be an early event in human breast neoplasia. A correlation was observed between HER2/neu expression and nucleocytoplasmic ß-catenin in node-positive carcinomas (P = 0.02. Furthermore, cytoplasmic ß-catenin was detected in HER2/neu-induced mouse mammary tumors. The Axin2(NLSlacZ mouse strain, a previously validated reporter of mammary Wnt/ß-catenin signaling, was utilized to define in vivo transcriptional consequences of HER2/neu-induced ß-catenin accumulation. Discrete hyperplastic foci observed in mammary

  12. Mechanisms in endocrinology: the crosstalk between thyroid gland and adipose tissue: signal integration in health and disease.

    Science.gov (United States)

    Santini, Ferruccio; Marzullo, Paolo; Rotondi, Mario; Ceccarini, Giovanni; Pagano, Loredana; Ippolito, Serena; Chiovato, Luca; Biondi, Bernadette

    2014-10-01

    Obesity and thyroid diseases are common disorders in the general population and they frequently occur in single individuals. Alongside a chance association, a direct relationship between 'thyroid and obesity' has been hypothesized. Thyroid hormone is an important determinant of energy expenditure and contributes to appetite regulation, while hormones and cytokines from the adipose tissue act on the CNS to inform on the quantity of energy stores. A continuous interaction between the thyroid hormone and regulatory mechanisms localized in adipose tissue and brain is important for human body weight control and maintenance of optimal energy balance. Whether obesity has a pathogenic role in thyroid disease remains largely a matter of investigation. This review highlights the complexity in the identification of thyroid hormone deficiency in obese patients. Regardless of the importance of treating subclinical and overt hypothyroidism, at present there is no evidence to recommend pharmacological correction of the isolated hyperthyrotropinemia often encountered in obese patients. While thyroid hormones are not indicated as anti-obesity drugs, preclinical studies suggest that thyromimetic drugs, by targeting selected receptors, might be useful in the treatment of obesity and dyslipidemia. © 2014 European Society of Endocrinology.

  13. Potential upstream regulators of cannabinoid receptor 1 signaling in prostate cancer: a Bayesian network analysis of data from a tissue microarray.

    Science.gov (United States)

    Häggström, Jenny; Cipriano, Mariateresa; Forshell, Linus Plym; Persson, Emma; Hammarsten, Peter; Stella, Nephi; Fowler, Christopher J

    2014-08-01

    The endocannabinoid system regulates cancer cell proliferation, and in prostate cancer a high cannabinoid CB1 receptor expression is associated with a poor prognosis. Down-stream mediators of CB1 receptor signaling in prostate cancer are known, but information on potential upstream regulators is lacking. Data from a well-characterized tumor tissue microarray were used for a Bayesian network analysis using the max-min hill-climbing method. In non-malignant tissue samples, a directionality of pEGFR (the phosphorylated form of the epidermal growth factor receptor) → CB1 receptors were found regardless as to whether the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) was included as a parameter. A similar result was found in the tumor tissue, but only when FAAH was included in the analysis. A second regulatory pathway, from the growth factor receptor ErbB2 → FAAH was also identified in the tumor samples. Transfection of AT1 prostate cancer cells with CB1 receptors induced a sensitivity to the growth-inhibiting effects of the CB receptor agonist CP55,940. The sensitivity was not dependent upon the level of receptor expression. Thus a high CB1 receptor expression alone does not drive the cells towards a survival phenotype in the presence of a CB receptor agonist. The data identify two potential regulators of the endocannabinoid system in prostate cancer and allow the construction of a model of a dysregulated endocannabinoid signaling network in this tumor. Further studies should be designed to test the veracity of the predictions of the network analysis in prostate cancer and other solid tumors. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc.

  14. Prevotella intermedia stimulates tissue-type plasminogen activator and plasminogen activator inhibitor-2 expression via multiple signaling pathways in human periodontal ligament cells.

    Science.gov (United States)

    Guan, Su-Min; He, Jian-Jun; Zhang, Ming; Shu, Lei

    2011-06-01

    Prevotella intermedia is an important periodontal pathogen that induces various inflammatory and immune responses. In this study, we investigated the effects of P. intermedia on the plasminogen system in human periodontal ligament (hPDL) cells and explored the signaling pathways involved. Using semi-quantitative reverse transcription (RT)-PCR and quantitative real-time RT-qPCR, we demonstrated that P. intermedia challenge increased tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-2 expression in a concentration- and time-dependent manner, but exerted no influence on urokinase-type plasminogen activator and PAI-1mRNA expression in hPDL cells. Prevotella intermedia stimulation also enhanced tPA protein secretion as confirmed by enzyme-linked immunosorbent assay. Western blot results revealed that P. intermedia treatment increased phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase (p38). ERK, JNK and protein kinase C inhibitors significantly attenuated the P. intermedia-induced tPA and PAI-2 expression. Furthermore, p38 and phosphatidylinositol 3-kinase inhibitors markedly decreased PAI-2 expression, whereas they showed no or little inhibition on tPA expression. In contrast, inhibition of protein kinase A greatly enhanced the upregulatory effect of P. intermedia on tPA and PAI-2 expression. Our results suggest that P. intermedia may contribute to periodontal tissue destruction by upregulating tPA and PAI-2 expression in hPDL cells via multiple signaling pathways. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  15. Oxidation of glucose-U-/sup 14/C and synthesis of glycogen in different tissues of the garden snail, Cryptozona ligulata with reference to aestivation and starvation

    Energy Technology Data Exchange (ETDEWEB)

    Krupanidhi, S; Raghavaiah, K; Padmanabha Naidu, B; Ramamurthi, R [Sri Venkateswara Univ., Tirupati (India). Dept. of Zoology

    1978-03-01

    The percent decrease of glycogen content in all the tissues investigated is more in 20-days starved snails than the 4-months aestivated snails when compared to active snails. Recovery of administered glucose-U/sup 14/C in the respiratory CO/sub 2/ is 42.27 % in active snails, whereas it is 8.81 % and 26.09 % in aestivated and starved snails respectively. Maximum levels of incorporation labelled glucose were found at 18 hr in all the tissues and the rate of incorporation was greatly elevated in the tissues of aestivated and starved snails. The causes for the difference in the rates of incorporation and the utilization of glycogen in active, aestivated and starved snails are discussed.

  16. Infection studies with two highly pathogenic avian influenza strains (Vietnamese and Indonesian) in Pekin ducks (Anas platyrhynchos), with particular reference to clinical disease, tissue tropism and viral shedding.

    Science.gov (United States)

    Bingham, John; Green, Diane J; Lowther, Sue; Klippel, Jessica; Burggraaf, Simon; Anderson, Danielle E; Wibawa, Hendra; Hoa, Dong Manh; Long, Ngo Thanh; Vu, Pham Phong; Middleton, Deborah J; Daniels, Peter W

    2009-08-01

    Pekin ducks were infected by the mucosal route (oral, nasal, ocular) with one of two strains of Eurasian lineage H5N1 highly pathogenic avian influenza virus: A/Muscovy duck/Vietnam/453/2004 and A/duck/Indramayu/BBVW/109/2006 (from Indonesia). Ducks were killed humanely on days 1, 2, 3, 5 and 7 after challenge, or whenever morbidity was severe enough to justify euthanasia. Morbidity was recorded by observation of clinical signs and cloacal temperatures; the disease was characterized by histopathology; tissue tropism was studied by immunohistochemistry and virus titration on tissue samples; and viral shedding patterns were determined by virus isolation and titration of oral and cloacal swabs. The Vietnamese strain caused severe morbidity with fever and depression; the Indonesian strain caused only transient fever. Both viruses had a predilection for a similar range of tissue types, but the quantity of tissue antigen and tissue virus titres were considerably higher with the Vietnamese strain. The Vietnamese strain caused severe myocarditis and skeletal myositis; both strains caused non-suppurative encephalitis and a range of other inflammatory reactions of varying severity. The principal epithelial tissue infected was that of the air sacs, but antigen was not abundant. Epithelium of the turbinates, trachea and bronchi had only rare infection with virus. Virus was shed from both the oral and cloacal routes; it was first detected 24 h after challenge and persisted until day 5 after challenge. The higher prevalence of virus from swabs from ducks infected with the Vietnamese strain indicates that this strain may be more adapted to ducks than the Indonesia strain.

  17. Electrical vs manual acupuncture stimulation in a rat model of polycystic ovary syndrome: different effects on muscle and fat tissue insulin signaling.

    Directory of Open Access Journals (Sweden)

    Julia Johansson

    Full Text Available In rats with dihydrotestosterone (DHT-induced polycystic ovary syndrome (PCOS, repeated low-frequency electrical stimulation of acupuncture needles restores whole-body insulin sensitivity measured by euglycemic hyperinsulinemic clamp. We hypothesized that electrical stimulation causing muscle contractions and manual stimulation causing needle sensation have different effects on insulin sensitivity and related signaling pathways in skeletal muscle and adipose tissue, with electrical stimulation being more effective in DHT-induced PCOS rats. From age 70 days, rats received manual or low-frequency electrical stimulation of needles in abdominal and hind limb muscle five times/wk for 4-5 wks; controls were handled but untreated rats. Low-frequency electrical stimulation modified gene expression (decreased Tbc1d1 in soleus, increased Nr4a3 in mesenteric fat and protein expression (increased pAS160/AS160, Nr4a3 and decreased GLUT4 by western blot and increased GLUT4 expression by immunohistochemistry in soleus muscle; glucose clearance during oral glucose tolerance tests was unaffected. Manual stimulation led to faster glucose clearance and modified mainly gene expression in mesenteric adipose tissue (increased Nr4a3, Mapk3/Erk, Adcy3, Gsk3b, but not protein expression to the same extent; however, Nr4a3 was reduced in soleus muscle. The novel finding is that electrical and manual muscle stimulation affect glucose homeostasis in DHT-induced PCOS rats through different mechanisms. Repeated electrical stimulation regulated key functional molecular pathways important for insulin sensitivity in soleus muscle and mesenteric adipose tissue to a larger extent than manual stimulation. Manual stimulation improved whole-body glucose tolerance, an effect not observed after electrical stimulation, but did not affect molecular signaling pathways to the same extent as electrical stimulation. Although more functional signaling pathways related to insulin sensitivity

  18. [Clinical effect modified Chevron osteotomy combined with lateral tissue loosening in treating mild-moderate hallux valgus through internal signal approach].

    Science.gov (United States)

    Chen, Xue-Qiang; Wu, Qun-Feng; Dong, Wei-Qin; Yu, Li-Xin; Li, Xiong-Feng

    2018-03-25

    To explore clinical effect of modified Chevron osteotomy combined with lateral tissue loosening for the treatment of mild-moderate hallux valgus through internal signal approach. From July 2015 to June 2016, 26 patients with mild-moderate hallux valgus treated with modified Chevron osteotomy combined with lateral tissue loosening through internal signal approach, including 2 males and 24 females aged from 45 to 65 years old with an average of(54.6±4.8) years old;the courses of diseases ranged from 1 to 5 months with an average of (7.5±3.3) months. Hallux valgus angle(HVA), inter metatarsal angle(IMA) were measured at 12 months after operation, and AOFAS score was applied to evaluate clinical effect before and after operation. All incisions were healed at stage I. No incision occurred infection, metatarsal necrosis and recurrence of hallux valgus deformity. Two patients occurred skin numbness caused by musculocutaneous nerve injury. Twenty-six patients were followed up from 6 to 12 months with an average of(9.12±2.06) months. HVA, IMA were(30.01±3.71)°, (14.00±1.50)° before operation and(9.41±4.16)°, (7.00±0.60)° after operation, which had significant difference. There was statistical significance in AOFAS score before operation 54.77±9.59 and after operation 92.73±5.47, and 19 cases obtained excellent results and 7 moderate. Modified Chevron osteotomy combined with full thread headless pressure screw fixation and lateral tissue loosening for the treatment of mild-moderate hallux valgus has advantages of excellent exposure, simple operation, stable fixation, rapid recovery. Akin osteotomy with internal capsulorrhaphy were used with lateral loosening and could recover soft tissue balance between lateral and internal, and could receive satisfied clinical effects. Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.

  19. Thromboxane A{sub 2} receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment

    Energy Technology Data Exchange (ETDEWEB)

    Minamino, Tsutomu [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ito, Yoshiya [Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ohkubo, Hirotoki [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Hosono, Kanako; Suzuki, Tatsunori [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sato, Takehito [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ae, Takako; Shibuya, Akitaka [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sakagami, Hiroyuki [Departments of Anatomy, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Narumiya, Shuh [Department of Pharmacology, Kyoto University School of Medicine, Kyoto, 606-8315 (Japan); Koizumi, Wasaburo [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Majima, Masataka, E-mail: mmajima@med.kitasato-u.ac.jp [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan)

    2012-02-15

    It is thought that thromboxane A{sub 2} (TxA{sub 2}) contributes to the progression of inflammation during acute hepatic injury; however, it is still unknown whether TxA{sub 2} is involved in liver repair. The objective of the present study was to examine the role of TxA{sub 2} receptor (TP) signaling in liver injury and repair in response to toxic injury. Carbon tetrachloride (CCl{sub 4}) was used to induce liver injury in TP knockout (TP{sup −/−}) mice and wild-type (WT) mice. In WT mice, serum levels of alanine aminotransferase (ALT) and the size of the necrotic area peaked at 24 and 48 h, respectively, and then declined. In TP{sup −/−} mice, the changes in ALT levels were similar to WT mice, but liver regeneration was impaired as evidenced by remained elevated levels of hepatic necrosis and by delayed hepatocyte proliferation, which was associated with the reduced expression of growth factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and hepatocyte growth factor (HGF). In TP{sup −/−} mice, the accumulation of hepatic CD11b{sup +}/F4/80{sup +} macrophages in injured livers was attenuated, and the hepatic expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, the C―C chemokine receptor (CCR2), was reduced compared to WT. Additionally, the application of the TP receptor agonist, U-46619, enhanced the expression of MCP-1/CCL2 and CCR2 in peritoneal macrophages, which was associated with increased levels of IL-6, TNFα and HGF. These results suggested that TP receptor signaling facilitates liver recovery following CCl{sub 4}-induced hepatotoxicity by affecting the expression of hepatotrophic growth factors, and through the recruitment of macrophages mediated by MCP-1/CCL2-CCR2 expression. -- Highlights: ► TP enhances liver regeneration by CCl{sub 4}. ► TP accumulates macrophages. ► TP up-regulates MCP-1.

  20. The relationships between the amount of spared tissue, percent signal change, and accuracy in semantic processing in aphasia.

    Science.gov (United States)

    Sims, Jordyn A; Kapse, Kushal; Glynn, Peter; Sandberg, Chaleece; Tripodis, Yorghos; Kiran, Swathi

    2016-04-01

    Recovery from aphasia, loss of language following a cerebrovascular incident (stroke), is a complex process involving both left and right hemispheric regions. In our study, we analyzed the relationships between semantic processing behavioral data, lesion size and location, and percent signal change from functional magnetic resonance imaging (fMRI) data. This study included 14 persons with aphasia in the chronic stage of recovery (six or more months post stroke), along with normal controls, who performed semantic processing tasks of determining whether a written semantic feature matched a picture or whether two written words were related. Using region of interest (ROI) analysis, we found that left inferior frontal gyrus pars opercularis and pars triangularis, despite significant damage, were the only regions to correlate with behavioral accuracy. Additionally, bilateral frontal regions including superior frontal gyrus, middle frontal gyrus, and anterior cingulate appear to serve as an assistive network in the case of damage to traditional language regions that include inferior frontal gyrus, middle temporal gyrus, supramarginal gyrus, and angular gyrus. Right hemisphere posterior regions including right middle temporal gyrus, right supramarginal gyrus, and right angular gyrus are engaged in the case of extensive damage to left hemisphere language regions. Additionally, right inferior frontal gyrus pars orbitalis is presumed to serve a monitoring function. These results reinforce the importance of the left hemisphere in language processing in aphasia, and provide a framework for the relative importance of left and right language regions in the brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Air pollution upregulates endothelial cell procoagulant activity via ultrafine particle-induced oxidant signaling and tissue factor expression.

    Science.gov (United States)

    Snow, S J; Cheng, W; Wolberg, A S; Carraway, M S

    2014-07-01

    Air pollution exposure is associated with cardiovascular events triggered by clot formation. Endothelial activation and initiation of coagulation are pathophysiological mechanisms that could link inhaled air pollutants to vascular events. Here we investigated the underlying mechanisms of increased endothelial cell procoagulant activity following exposure to soluble components of ultrafine particles (soluble UF). Human coronary artery endothelial cells (HCAEC) were exposed to soluble UF and assessed for their ability to trigger procoagulant activity in platelet-free plasma. Exposed HCAEC triggered earlier thrombin generation and faster fibrin clot formation, which was abolished by an anti-tissue factor (TF) antibody, indicating TF-dependent effects. Soluble UF exposure increased TF mRNA expression without compensatory increases in key anticoagulant proteins. To identify early events that regulate TF expression, we measured endothelial H2O2 production following soluble UF exposure and identified the enzymatic source. Soluble UF exposure increased endothelial H2O2 production, and antioxidants attenuated UF-induced upregulation of TF, linking the procoagulant responses to reactive oxygen species (ROS) formation. Chemical inhibitors and RNA silencing showed that NOX-4, an important endothelial source of H2O2, was involved in UF-induced upregulation of TF mRNA. These data indicate that soluble UF exposure induces endothelial cell procoagulant activity, which involves de novo TF synthesis, ROS production, and the NOX-4 enzyme. These findings provide mechanistic insight into the adverse cardiovascular effects associated with air pollution exposure. Published by Oxford University Press on behalf of Toxicological Sciences 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Resistin Enhances Inflammatory Cytokine Production in Coronary Artery Tissues by Activating the NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Fang Gao

    2016-01-01

    Full Text Available Purpose. Kawasaki disease (KD is a systemic vasculitis and is a leading cause of coronary artery lesions (CALs in childhood. Our previous study has shown higher levels of serum Resistin in KD patients with coronary aneurysm. This study aimed at examining the association of Resistin with inflammatory cytokine expression in mouse model of coronary arteritis and determining the potential mechanisms. Methods. C57BL/6 mice were injected with Lactobacillus cell wall extract (LCWE to induce coronary arteritis. The relative levels of Resistin, TNF-α, IL-1β, and MMP-9 expression and inflammatory infiltrates in the coronary arteries were determined longitudinally by quantitative RT-PCR, ELISA, and histology. The effect of TLR4 and NF-κB activation on Resistin-induced TNF-α and IL-1β expression in human coronary artery endothelium cells (HCAECs was examined by quantitative RT-PCR. Results. Higher levels of Resistin, TNF-α, IL-1β, and MMP-9 expression were associated with the degrees of inflammatory infiltrates in the coronary artery walls of the LCWE-injected mice. Resistin enhanced TNF-α and IL-1β expression in HCAECs at 18 or 24 hours after stimulation. Pretreatment with anti-TLR4 attenuated Resistin-enhanced IL-1β, but not TNF-α, expression and pretreatment with parthenolide or QNZ demolished Resistin-enhanced TNF-α expression in HACECs. Pretreatment with parthenolide, but not QNZ, blocked Resistin-enhanced IL-1β expression in HCAECs. Conclusion. Resistin may enhance inflammation by cross-talking with TLR4/NF-κB signaling during the development of coronary arteritis in mice.

  3. Influence of the Laser Spot Size, Focal Beam Profile, and Tissue Type on the Lipid Signals Obtained by MALDI-MS Imaging in Oversampling Mode.

    Science.gov (United States)

    Wiegelmann, Marcel; Dreisewerd, Klaus; Soltwisch, Jens

    2016-12-01

    To improve the lateral resolution in matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) beyond the dimensions of the focal laser spot oversampling techniques are employed. However, few data are available on the effect of the laser spot size and its focal beam profile on the ion signals recorded in oversampling mode. To investigate these dependencies, we produced 2 times six spots with dimensions between ~30 and 200 μm. By optional use of a fundamental beam shaper, square flat-top and Gaussian beam profiles were compared. MALDI-MSI data were collected using a fixed pixel size of 20 μm and both pixel-by-pixel and continuous raster oversampling modes on a QSTAR mass spectrometer. Coronal mouse brain sections coated with 2,5-dihydroxybenzoic acid matrix were used as primary test systems. Sizably higher phospholipid ion signals were produced with laser spots exceeding a dimension of ~100 μm, although the same amount of material was essentially ablated from the 20 μm-wide oversampling pixel at all spot size settings. Only on white matter areas of the brain these effects were less apparent to absent. Scanning electron microscopy images showed that these findings can presumably be attributed to different matrix morphologies depending on tissue type. We propose that a transition in the material ejection mechanisms from a molecular desorption at large to ablation at smaller spot sizes and a concomitant reduction in ion yields may be responsible for the observed spot size effects. The combined results indicate a complex interplay between tissue type, matrix crystallization, and laser-derived desorption/ablation and finally analyte ionization. Graphical Abstract ᅟ.

  4. Diffusion-weighted magnetic resonance imaging for the initial characterization of non-fatty soft tissue tumors: correlation between T2 signal intensity and ADC values

    Energy Technology Data Exchange (ETDEWEB)

    Gondim Teixeira, Pedro Augusto [Service d' Imagerie Guilloz, CHU Nancy, Nancy (France); Universite de Lorraine, IADI, UMR S 947, Vandoeuvre-les-Nancy (France); Gay, Frederique; Blum, Alain [Service d' Imagerie Guilloz, CHU Nancy, Nancy (France); Chen, Bailiang; Felblinger, Jacques [Universite de Lorraine, IADI, UMR S 947, Vandoeuvre-les-Nancy (France); Zins, Marie [University Versailles St-Quentin, Versailles (France); Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Villejuif (France); Sirveaux, Francois [Centre Chirurgical Emile Galle, Service de Chirurgie Traumatologique et Orthopedique, Nancy (France)

    2016-02-15

    To evaluate the performance of quantitative diffusion-weighted imaging (DWI) correlated with T2 signal in differentiating non-fatty benign from malignant tumors. A total of 76 patients with a histologically confirmed non-fatty soft tissue tumors (46 benign and 30 malignant) were prospectively included in this ethics committee approved study. All patients signed an informed consent and underwent MRI with DWI with two b values (0 and 600). ADC values from the solid components of these tumors were obtained and were correlated with the lesion's signal intensity on T2-weighted fat-saturated sequences. ADC values were obtained from adjacent normal muscle to allow calculation of tumor/muscle ADC ratios. There were 58 hyperintense and 18 iso or hypointense lesions. All hypointense lesions were benign. The mean ADC values for benign and malignant tumors were 1.47 ± 0.54 x 10{sup -3} and 1.17 ± 0.38 x 10{sup -3} mm{sup 2}/s respectively (p < 0.005). The mean ADC ratio in benign iso or hypointense tumors was significantly lower than that of hyperintense ones (0.76 ± 0.21 versus 1.58 ± 0.82 - p < 0.0001). An ADC ratio lower than 0.915 was highly specific for malignancy (96.4 %), whereas an ADC ratio higher than 1.32 was highly sensitive for benign lesions (90 %). ADC analysis can be useful in the initial characterization of T2 hyperintense non-fatty soft tissue masses, although this technique alone is not likely to change patient management. (orig.)

  5. Automated Spatial Brain Normalization and Hindbrain White Matter Reference Tissue Give Improved [(18)F]-Florbetaben PET Quantitation in Alzheimer's Model Mice.

    Science.gov (United States)

    Overhoff, Felix; Brendel, Matthias; Jaworska, Anna; Korzhova, Viktoria; Delker, Andreas; Probst, Federico; Focke, Carola; Gildehaus, Franz-Josef; Carlsen, Janette; Baumann, Karlheinz; Haass, Christian; Bartenstein, Peter; Herms, Jochen; Rominger, Axel

    2016-01-01

    Preclinical PET studies of β-amyloid (Aβ) accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore, we aimed to evaluate systematically the (1) impact of an automated algorithm for spatial brain normalization, and (2) intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a 6 week longitudinal setting (N = 37) and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40) were investigated by [(18)F]-florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ). For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX∕REF), relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen's d), and in reference to gold standard histopathological quantitation (Pearson's R). Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ≥0.99) between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX∕REF. All SUVRCTX∕REF methods performed better than SUVCTX both with regard to longitudinal stability (d≥1.21 vs. d = 0.23) and histological gold standard agreement (R≥0.66 vs. R≥0.31). Voxel-wise analysis suggested a physiologically implausible longitudinal decrease by global mean scaling. The hindbrain white matter reference (R mean = 0.75) was slightly superior to the brainstem (R mean = 0.74) and the cerebellum (R mean = 0.73). Automated

  6. Steroidal androgens and nonsteroidal, tissue-selective androgen receptor modulator, S-22, regulate androgen receptor function through distinct genomic and nongenomic signaling pathways.

    Science.gov (United States)

    Narayanan, Ramesh; Coss, Christopher C; Yepuru, Muralimohan; Kearbey, Jeffrey D; Miller, Duane D; Dalton, James T

    2008-11-01

    Androgen receptor (AR) ligands are important for the development and function of several tissues and organs. However, the poor oral bioavailability, pharmacokinetic properties, and receptor cross-reactivity of testosterone, coupled with side effects, place limits on its clinical use. Selective AR modulators (SARMs) elicit anabolic effects in muscle and bone, sparing reproductive organs like the prostate. However, molecular mechanisms underlying the tissue selectivity remain ambiguous. We performed a variety of in vitro studies to compare and define the molecular mechanisms of an aryl propionamide SARM, S-22, as compared with dihydrotestosterone (DHT). Studies indicated that S-22 increased levator ani muscle weight but decreased the size of prostate in rats. Analysis of the upstream intracellular signaling events indicated that S-22 and DHT mediated their actions through distinct pathways. Modulation of these pathways altered the recruitment of AR and its cofactors to the PSA enhancer in a ligand-dependent fashion. In addition, S-22 induced Xenopus laevis oocyte maturation and rapid phosphorylation of several kinases, through pathways distinct from steroids. These studies reveal novel differences in the molecular mechanisms by which S-22, a nonsteroidal SARM, and DHT mediate their pharmacological effects.

  7. Exogenous Bradykinin Inhibits Tissue Factor Induction and Deep Vein Thrombosis via Activating the eNOS/Phosphoinositide 3-Kinase/Akt Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Ruolan Dong

    2015-11-01

    Full Text Available Background/Aims: Bradykinin has been shown to exert a variety of protective effects against vascular injury, and to reduce the levels of several factors involved in the coagulation cascade. A key determinant of thrombin generation is tissue factor (TF. However, whether bradykinin can regulate TF expression remains to be investigated. Methods: To study the effect of bradykinin on TF expression, we used Lipopolysaccharides (LPS to induce TF expression in human umbilical vein endothelial cells and monocytes. Transcript levels were determined by RT-PCR, protein abundance by Western blotting. In the in vivo study, bradykinin and equal saline were intraperitoneally injected into mice for three days ahead of inferior cava vein ligation that we took to induce thrombus formation, after which bradykinin and saline were injected for another two days. Eventually, the mice were sacrificed and tissues were harvested for tests. Results: Exogenous bradykinin markedly inhibited TF expression in mRNA and protein level induced by LPS in a dose-dependent manner. Moreover, the NO synthase antagonist L-NAME and PI3K inhibitor LY294002 dramatically abolished the inhibitory effects of bradykinin on tissue factor expression. PI3K/Akt signaling pathway activation induced by bradykinin administration reduced the activity of GSK-3ß and MAPK, and reduced NF-κB level in the nucleus, thereby inhibiting TF expression. Consistent with this, intraperitoneal injection of C57/BL6 mice with bradykinin also inhibited the thrombus formation induced by ligation of inferior vena cava. Conclusion: Bradykinin suppressed TF protein expression in human umbilical vein endothelial cells and monocytes in vitro; in line with this, it inhibits thrombus formation induced by ligation of inferior vena cava in vivo.

  8. L-carnitine mitigates UVA-induced skin tissue injury in rats through downregulation of oxidative stress, p38/c-Fos signaling, and the proinflammatory cytokines.

    Science.gov (United States)

    Salama, Samir A; Arab, Hany H; Omar, Hany A; Gad, Hesham S; Abd-Allah, Gamil M; Maghrabi, Ibrahim A; Al Robaian, Majed M

    2018-04-01

    UVA comprises more than 90% of the solar UV radiation reaching the Earth. Artificial lightening lamps have also been reported to emit significant amounts of UVA. Exposure to UVA has been associated with dermatological disorders including skin cancer. At the molecular level, UVA damages different cellular biomolecules and triggers inflammatory responses. The current study was devoted to investigate the potential protective effect of L-carnitine against UVA-induced skin tissue injury using rats as a mammalian model. Rats were distributed into normal control group (NC), L-carnitine control group (LC), UVA-Exposed group (UVA), and UVA-Exposed and L-carnitine-treated group (UVA-LC). L-carnitine significantly attenuated UVA-induced elevation of the DNA damage markers 8-oxo-2'-deoxyguanosine (8-oxo-dG) and cyclobutane pyrimidine dimers (CPDs) as well as decreased DNA fragmentation and the activity of the apoptotic marker caspase-3. In addition, L-carnitine substantially reduced the levels of lipid peroxidation marker (TBARS) and protein oxidation marker (PCC) and significantly elevated the levels of the total antioxidant capacity (TAC) and the antioxidant reduced glutathione (GSH) in the skin tissues. Interestingly, L-carnitine upregulated the level of the DNA repair protein proliferating cell nuclear antigen (PCNA). Besides it mitigated the UVA-induced activation of the oxidative stress-sensitive signaling protein p38 and its downstream target c-Fos. Moreover, L-carnitine significantly downregulated the levels of the early response proinflammatory cytokines TNF-α, IL-6, and IL-1β. Collectively, our results highlight, for the first time, the potential attenuating effects of L-carnitine on UVA-induced skin tissue injury in rats that is potentially mediated through suppression of UVA-induced oxidative stress and inflammatory responses. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Examination of the signal transduction pathways leading to upregulation of tissue type plasminogen activator by Porphyromonas endodontalis in human pulp cells.

    Science.gov (United States)

    Huang, F-M; Chen, Y-J; Chou, M-Y; Chang, Y-C

    2005-12-01

    To investigate the tissue type plasminogen activator (t-PA) activity in human pulp cells stimulated with Porphyromonas endodontalis (P. endodontalis) in the absence or presence of p38 inhibitor SB203580, mitogen-activated protein kinase kinase (MEK) inhibitor U0126 and phosphatidylinositaol 3-kinase (PI3K) inhibitor LY294002. The supernatants of P. endodontalis were used to evaluate t-PA activity in human pulp cells using casein zymography and enzyme-linked immunosorbent assay (ELISA). Furthermore, to search for possible signal transduction pathways, SB203580, U0126 and LY294002 were added to test how they modulated the t-PA activity. The main casein secreted by human pulp cells migrated at 70 kDa and represented t-PA. Secretion of t-PA was found to be stimulated with P. endodontalis during 2-day cultured period (P endodontalis stimulated t-PA production respectively (P endodontalis stimulated t-PA production (P > 0.05). Porphyromonas endodontalis enhances t-PA production in human pulp cells, and the signal transduction pathways p38 and MEK are involved in the inhibition of t-PA.

  10. Bone to pick: the importance of evaluating reference genes for RT-qPCR quantification of gene expression in craniosynostosis and bone-related tissues and cells

    Directory of Open Access Journals (Sweden)

    Yang Xianxian

    2012-05-01

    Full Text Available Abstract Background RT-qPCR is a common tool for quantification of gene expression, but its accuracy is dependent on the choice and stability (steady state expression levels of the reference gene/s used for normalization. To date, in the bone field, there have been few studies to determine the most stable reference genes and, usually, RT-qPCR data is normalised to non-validated reference genes, most commonly GAPDH, ACTB and 18 S rRNA. Here we draw attention to the potential deleterious impact of using classical reference genes to normalise expression data for bone studies without prior validation of their stability. Results Using the geNorm and Normfinder programs, panels of mouse and human genes were assessed for their stability under three different experimental conditions: 1 disease progression of Crouzon syndrome (craniosynostosis in a mouse model, 2 proliferative culture of cranial suture cells isolated from craniosynostosis patients and 3 osteogenesis of a mouse bone marrow stromal cell line. We demonstrate that classical reference genes are not always the most ‘stable’ genes and that gene ‘stability’ is highly dependent on experimental conditions. Selected stable genes, individually or in combination, were then used to normalise osteocalcin and alkaline phosphatase gene expression data during cranial suture fusion in the craniosynostosis mouse model and strategies compared. Strikingly, the expression trends of alkaline phosphatase and osteocalcin varied significantly when normalised to the least stable, the most stable or the three most stable genes. Conclusion To minimise errors in evaluating gene expression levels, analysis of a reference panel and subsequent normalization to several stable genes is strongly recommended over normalization to a single gene. In particular, we conclude that use of single, non-validated “housekeeping” genes such as GAPDH, ACTB and 18 S rRNA, currently a widespread practice by researchers in

  11. Comparison of contrast-to-noise ratios of transmission and dark-field signal in grating-based X-ray imaging for healthy murine lung tissue

    International Nuclear Information System (INIS)

    Schwab, Felix; Schleede, Simone; Hahn, Dieter

    2013-01-01

    Purpose: An experimental comparison of the contrast-to-noise ratio (CNR) between transmission and dark-field signals in grating-based X-ray imaging for ex-vivo murine lung tissue. Materials and Methods: Lungs from three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Background noise of transmission and dark-field signal was quantified by measuring the standard deviation in a region of interest (ROI) placed in a homogeneous area outside the specimen. Image contrast was quantified by measuring the signal range in rectangular ROIs placed in central and peripheral lung parenchyma. The relative contrast gain (RCG) of dark-field over transmission images was calculated as CNRDF / CNRT. Results: In all images, there was a trend for contrast-to-noise ratios of dark-field images (CNRDF) to be higher than for transmission images (CNRT) for all ROIs (median 61 vs. 38, p = 0.10), but the difference was statistically significant only for peripheral ROIs (61 vs. 32, p = 0.03). Median RCG was >1 for all ROIs (1.84). RCG values were significantly smaller for central ROIs than for peripheral ROIs (1.34 vs. 2.43, p = 0.03). Conclusion: The contrast-to-noise ratio of dark-field images compares more favorably to the contrast-to-noise ratio of transmission images for peripheral lung regions as compared to central regions. For any specific specimen, a calculation of the RCG allows comparing which X-ray modality (dark-field or transmission imaging) produces better contrast-to-noise characteristics in a well-defined ROI. (orig.)

  12. Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ying [Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 (China); Wang, Jianwei, E-mail: wangjianwei1968@gmail.com [Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016 (China); Gu, Tieguang [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences, Sydney, NSW 2000 Australia (Australia); Yamahara, Johji [Pharmafood Institute, Kyoto 602-8136 (Japan); Li, Yuhao, E-mail: yuhao@sitcm.edu.au [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences, Sydney, NSW 2000 Australia (Australia)

    2014-06-01

    Oleanolic acid, a triterpenoid contained in more than 1620 plants including various fruits and foodstuffs, has numerous metabolic effects, such as hepatoprotection. However, its underlying mechanisms remain poorly understood. Adipose tissue insulin resistance (Adipo-IR) may contribute to the development and progress of metabolic abnormalities through release of excessive free fatty acids from adipose tissue. This study investigated the effect of oleanolic acid on Adipo-IR. The results showed that supplement with oleanolic acid (25 mg/kg, once daily, by oral gavage) over 10 weeks attenuated liquid fructose-induced increase in plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. Simultaneously, oleanolic acid reversed the increase in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment. In white adipose tissue, oleanolic acid enhanced mRNA expression of the genes encoding insulin receptor, insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase. At the protein level, oleanolic acid upregulated total IRS-1 expression, suppressed the increased phosphorylated IRS-1 at serine-307, and restored the increased phosphorylated IRS-1 to total IRS-1 ratio. In contrast, phosphorylated Akt to total Akt ratio was increased. Furthermore, oleanolic acid reversed fructose-induced decrease in phosphorylated-Akt/Akt protein to plasma insulin concentration ratio. However, oleanolic acid did not affect IRS-2 mRNA expression. Therefore, these results suggest that oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway. Our findings may provide new insights into the mechanisms of metabolic actions of oleanolic acid. - Highlights: • Adipose insulin resistance (Adipo-IR) contributes to metabolic abnormalities. • We investigated the effect of oleanolic acid (OA) on adipo-IR in

  13. Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats

    International Nuclear Information System (INIS)

    Li, Ying; Wang, Jianwei; Gu, Tieguang; Yamahara, Johji; Li, Yuhao

    2014-01-01

    Oleanolic acid, a triterpenoid contained in more than 1620 plants including various fruits and foodstuffs, has numerous metabolic effects, such as hepatoprotection. However, its underlying mechanisms remain poorly understood. Adipose tissue insulin resistance (Adipo-IR) may contribute to the development and progress of metabolic abnormalities through release of excessive free fatty acids from adipose tissue. This study investigated the effect of oleanolic acid on Adipo-IR. The results showed that supplement with oleanolic acid (25 mg/kg, once daily, by oral gavage) over 10 weeks attenuated liquid fructose-induced increase in plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. Simultaneously, oleanolic acid reversed the increase in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment. In white adipose tissue, oleanolic acid enhanced mRNA expression of the genes encoding insulin receptor, insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase. At the protein level, oleanolic acid upregulated total IRS-1 expression, suppressed the increased phosphorylated IRS-1 at serine-307, and restored the increased phosphorylated IRS-1 to total IRS-1 ratio. In contrast, phosphorylated Akt to total Akt ratio was increased. Furthermore, oleanolic acid reversed fructose-induced decrease in phosphorylated-Akt/Akt protein to plasma insulin concentration ratio. However, oleanolic acid did not affect IRS-2 mRNA expression. Therefore, these results suggest that oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway. Our findings may provide new insights into the mechanisms of metabolic actions of oleanolic acid. - Highlights: • Adipose insulin resistance (Adipo-IR) contributes to metabolic abnormalities. • We investigated the effect of oleanolic acid (OA) on adipo-IR in

  14. Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling

    International Nuclear Information System (INIS)

    Cucinotta, Francis A

    2016-01-01

    The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently, the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses, and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low-dose responses and cross-talk between the ATM and TGFβ pathways initiated by low- and high-LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to crosstalk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

  15. Systems Biology Model of Interactions Between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFbeta and ATM Signaling

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, Peter [University of Oxford; Anderson, Jennifer [University of Oxford

    2014-10-02

    The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low dose responses and cross-talk between the ATM and TGFβ pathways initiated by low and high LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to cross- talk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

  16. Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Cucinotta, Francis A [Univ. of Nevada, Las Vegas, NV (United States)

    2016-09-01

    The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently, the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses, and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low-dose responses and cross-talk between the ATM and TGFβ pathways initiated by low- and high-LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to crosstalk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

  17. Intraoperative radiotherapy in combination with misonidazole. In special reference to the drug concentration in tumors and normal tissues and to the initial effect of the treatment

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Masaji; Ono, Kouji; Hamanaka, Daizaburo; Dodo, Yoshihiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Faculty of Medicine

    1983-03-01

    A hypoxic cell radiosensitizer, misonidazole, was applied to 28 patients with carcinoma who received intraoperative radiotherapy. A single dose of 2-3g/m/sup 2/ of the drug was given orally to each patient three hours prior to the start of general anesthesia. The levels of misonidazole and its metabolite, desmethylmisonidazole, in blood, tumors and normal tissues taken from excised materials were measured by a high performance liquid chromatography. The results showed that the concentration levels of misonidazole and desmethylmisonidazole in blood correlated neither to oral doses of 2-3g/m/sup 2/ nor to the function of time after drug ingestion until eight hours. The mean value of blood levels was 77.1 +- 10.9..mu..g/ml. A wide range of 10-96% of the blood level was found in tumors. High levels were observed in gastric cancer and brain tumor (glioblastoma) but not in colorectal cancer and osteosarcoma. It was, however, likely that the concentrations in tumors depended on tumor sizes and/or necrotic areas rather than histologic types and/or sites of tumors. It was also noted that the concentration in normal tissues ranged widely from 11 to 87% of the blood level. Higher concentrations showing more than 75% were found in the ulnar nerve, the stomach and the skin. However, 3 of 4 materials for the stomach and 2 of 3 materials for the skin showed low levels of less than 30% and less than 22% respectively. In 27 of 28 cases different doses of 28-50 Gy with different energies of electrons were delivered intraoperatively. It is impossible so far to derive conclusive results of this study, really because of the short period of observation following the treatment.

  18. Plant tissue culture techniques

    Directory of Open Access Journals (Sweden)

    Rolf Dieter Illg

    1991-01-01

    Full Text Available Plant cell and tissue culture in a simple fashion refers to techniques which utilize either single plant cells, groups of unorganized cells (callus or organized tissues or organs put in culture, under controlled sterile conditions.

  19. Developmental cuprizone exposure impairs oligodendrocyte lineages differentially in cortical and white matter tissues and suppresses glutamatergic neurogenesis signals and synaptic plasticity in the hippocampal dentate gyrus of rats

    International Nuclear Information System (INIS)

    Abe, Hajime; Saito, Fumiyo; Tanaka, Takeshi; Mizukami, Sayaka; Hasegawa-Baba, Yasuko; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2016-01-01

    Developmental cuprizone (CPZ) exposure impairs rat hippocampal neurogenesis. Here, we captured the developmental neurotoxicity profile of CPZ using a region-specific expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex and cerebellar vermis of rat offspring exposed to 0, 0.1, or 0.4% CPZ in the maternal diet from gestation day 6 to postnatal day (PND) 21. Transcripts of those genes identified as altered were subjected to immunohistochemical analysis on PNDs 21 and 77. Our results showed that transcripts for myelinogenesis-related genes, including Cnp, were selectively downregulated in the cerebral cortex by CPZ at ≥ 0.1% or 0.4% on PND 21. CPZ at 0.4% decreased immunostaining intensity for 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase) and CNPase + and OLIG2 + oligodendrocyte densities in the cerebral cortex, whereas CNPase immunostaining intensity alone was decreased in the corpus callosum. By contrast, a striking transcript upregulation for Klotho gene and an increased density of Klotho + oligodendrocytes were detected in the corpus callosum at ≥ 0.1%. In the dentate gyrus, CPZ at ≥ 0.1% or 0.4% decreased the transcript levels for Gria1, Grin2a and Ptgs2, genes related to the synapse and synaptic transmission, and the number of GRIA1 + and GRIN2A + hilar γ-aminobutyric acid (GABA)-ergic interneurons and cyclooxygenase-2 + granule cells. All changes were reversed at PND 77. Thus, developmental CPZ exposure reversibly decreased mature oligodendrocytes in both cortical and white matter tissues, and Klotho protected white matter oligodendrocyte growth. CPZ also reversibly targeted glutamatergic signals of GABAergic interneuron to affect dentate gyrus neurogenesis and synaptic plasticity in granule cells. - Highlights: • We examined developmental cuprizone (CPZ) neurotoxicity in maternally exposed rats. • Multiple brain region-specific global gene expression profiling was performed. • CPZ decreased

  20. Developmental cuprizone exposure impairs oligodendrocyte lineages differentially in cortical and white matter tissues and suppresses glutamatergic neurogenesis signals and synaptic plasticity in the hippocampal dentate gyrus of rats

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Hajime [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Saito, Fumiyo [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Tanaka, Takeshi; Mizukami, Sayaka [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Hasegawa-Baba, Yasuko [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Imatanaka, Nobuya; Akahori, Yumi [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Yoshida, Toshinori [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

    2016-01-01

    Developmental cuprizone (CPZ) exposure impairs rat hippocampal neurogenesis. Here, we captured the developmental neurotoxicity profile of CPZ using a region-specific expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex and cerebellar vermis of rat offspring exposed to 0, 0.1, or 0.4% CPZ in the maternal diet from gestation day 6 to postnatal day (PND) 21. Transcripts of those genes identified as altered were subjected to immunohistochemical analysis on PNDs 21 and 77. Our results showed that transcripts for myelinogenesis-related genes, including Cnp, were selectively downregulated in the cerebral cortex by CPZ at ≥ 0.1% or 0.4% on PND 21. CPZ at 0.4% decreased immunostaining intensity for 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase) and CNPase{sup +} and OLIG2{sup +} oligodendrocyte densities in the cerebral cortex, whereas CNPase immunostaining intensity alone was decreased in the corpus callosum. By contrast, a striking transcript upregulation for Klotho gene and an increased density of Klotho{sup +} oligodendrocytes were detected in the corpus callosum at ≥ 0.1%. In the dentate gyrus, CPZ at ≥ 0.1% or 0.4% decreased the transcript levels for Gria1, Grin2a and Ptgs2, genes related to the synapse and synaptic transmission, and the number of GRIA1{sup +} and GRIN2A{sup +} hilar γ-aminobutyric acid (GABA)-ergic interneurons and cyclooxygenase-2{sup +} granule cells. All changes were reversed at PND 77. Thus, developmental CPZ exposure reversibly decreased mature oligodendrocytes in both cortical and white matter tissues, and Klotho protected white matter oligodendrocyte growth. CPZ also reversibly targeted glutamatergic signals of GABAergic interneuron to affect dentate gyrus neurogenesis and synaptic plasticity in granule cells. - Highlights: • We examined developmental cuprizone (CPZ) neurotoxicity in maternally exposed rats. • Multiple brain region-specific global gene expression profiling

  1. Dual turn-on fluorescence signal-based controlled release system for real-time monitoring of drug release dynamics in living cells and tumor tissues.

    Science.gov (United States)

    Kong, Xiuqi; Dong, Baoli; Song, Xuezhen; Wang, Chao; Zhang, Nan; Lin, Weiying

    2018-01-01

    Controlled release systems with capabilities for direct and real-time monitoring of the release and dynamics of drugs in living systems are of great value for cancer chemotherapy. Herein, we describe a novel dual turn-on fluorescence signal-based controlled release system ( CDox ), in which the chemotherapy drug doxorubicin ( Dox ) and the fluorescent dye ( CH ) are conjugated by a hydrazone moiety, a pH-responsive cleavable linker. CDox itself shows nearly no fluorescence as the fluorescence of CH and Dox is essentially quenched by the C=N isomerization and N-N free rotation. However, when activated under acidic conditions, CDox could be hydrolyzed to afford Dox and CH , resulting in dual turn-on signals with emission peaks at 595 nm and 488 nm, respectively. Notably, CDox exhibits a desirable controlled release feature as the hydrolysis rate is limited by the steric hindrance effect from both the Dox and CH moieties. Cytotoxicity assays indicate that CDox shows much lower cytotoxicity relative to Dox , and displays higher cell inhibition rate to cancer than normal cells. With the aid of the dual turn-on fluorescence at different wavelengths, the drug release dynamics of CDox in living HepG2 and 4T-1 cells was monitored in double channels in a real-time fashion. Importantly, two-photon fluorescence imaging of CDox in living tumor tissues was also successfully performed by high-definition 3D imaging. We expect that the unique controlled release system illustrated herein could provide a powerful means to investigate modes of action of drugs, which is critical for development of much more robust and effective chemotherapy drugs.

  2. Neoproteoglycans in tissue engineering

    Science.gov (United States)

    Weyers, Amanda; Linhardt, Robert J.

    2014-01-01

    Proteoglycans, comprised of a core protein to which glycosaminoglycan chains are covalently linked, are an important structural and functional family of macromolecules found in the extracellular matrix. Advances in our understanding of biological interactions have lead to a greater appreciation for the need to design tissue engineering scaffolds that incorporate mimetics of key extracellular matrix components. A variety of synthetic and semisynthetic molecules and polymers have been examined by tissue engineers that serve as structural, chemical and biological replacements for proteoglycans. These proteoglycan mimetics have been referred to as neoproteoglycans and serve as functional and therapeutic replacements for natural proteoglycans that are often unavailable for tissue engineering studies. Although neoproteoglycans have important limitations, such as limited signaling ability and biocompatibility, they have shown promise in replacing the natural activity of proteoglycans through cell and protein binding interactions. This review focuses on the recent in vivo and in vitro tissue engineering applications of three basic types of neoproteoglycan structures, protein–glycosaminoglycan conjugates, nano-glycosaminoglycan composites and polymer–glycosaminoglycan complexes. PMID:23399318

  3. In Inflamed Intestinal Tissues and Epithelial Cells, Interleukin 22 Signaling Increases Expression of H19 Long Noncoding RNA, Which Promotes Mucosal Regeneration.

    Science.gov (United States)

    Geng, Hua; Bu, Heng-Fu; Liu, Fangyi; Wu, Longtao; Pfeifer, Karl; Chou, Pauline M; Wang, Xiao; Sun, Jiaren; Lu, Lu; Pandey, Ashutosh; Bartolomei, Marisa S; De Plaen, Isabelle G; Wang, Peng; Yu, Jindan; Qian, Jiaming; Tan, Xiao-Di

    2018-04-03

    Inflammation affects regeneration of the intestinal epithelia; long non-coding RNAs (lncRNAs) regulate cell functions, such as proliferation, differentiation, and migration. We investigated the mechanisms by which the lncRNA H19, imprinted maternally expressed transcript (H19) regulates regeneration of intestinal epithelium using cell cultures and mouse models of inflammation. We performed RNA-sequencing transcriptome analyses of intestinal tissues from mice with lipopolysaccharide (LPS)-induced sepsis to identify lncRNAs associated with inflammation; findings were confirmed by quantitative real-time polymerase chain reaction and in situ hybridization analyses of intestinal tissues from mice with sepsis or dextran sulfate sodium (DSS)-induced mucosal wound healing and patients with ulcerative colitis compared to healthy individuals (controls). We screened cytokines for their ability to induce expression of H19 in HT-29 cells and intestinal epithelial cells (IECs), and confirmed findings in crypt epithelial organoids derived from mouse small intestine. IECs were incubated with different signal transduction inhibitors and effects on H19 lncRNA levels were measured. We assessed intestinal epithelial proliferation or regeneration in H19 ΔEx1/+ mice given LPS or DSS vs wild-type littermates (control mice). H19 was overexpressed in IECs using lentiviral vectors and cell proliferation was measured. We performed RNA antisense purification, RNA immunoprecipitation, and luciferase reporter assays to study functions of H19 in IECs. In RNA-sequencing transcriptome analysis of lncRNA expression in intestinal tissues from mice, we found levels of H19 only changed significantly with LPS exposure. Levels of H19 lncRNA increased in intestinal tissues of patients with ulcerative colitis, mice with LPS-induced sepsis, or mice with DSS-induced colitis, compared with controls. Increased H19 lncRNA localized to epithelial cells in the intestine, regardless of Lgr5 messenger RNA

  4. P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non-small-cell lung cancer.

    Science.gov (United States)

    Kato, Shinichiro; Yokoyama, Satoru; Hayakawa, Yoshihiro; Li, Luhui; Iwakami, Yusuke; Sakurai, Hiroaki; Saiki, Ikuo

    2016-10-01

    Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non-small-cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC-14, A549, and PC-9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  5. Growth references

    NARCIS (Netherlands)

    Buuren, S. van

    2007-01-01

    A growth reference describes the variation of an anthropometric measurement within a group of individuals. A reference is a tool for grouping and analyzing data and provides a common basis for comparing populations.1 A well known type of reference is the age-conditional growth diagram. The

  6. Smad signaling pathway is a pivotal component of tissue inhibitor of metalloproteinases-3 regulation by transforming growth factor beta in human chondrocytes.

    Science.gov (United States)

    Qureshi, Hamid Yaqoob; Ricci, Gemma; Zafarullah, Muhammad

    2008-09-01

    Transforming growth factor beta (TGF-beta1) promotes cartilage matrix synthesis and induces tissue inhibitor of metalloproteinases-3 (TIMP-3), which inhibits matrix metalloproteinases, aggrecanases and TNF-alpha-converting enzyme implicated in articular cartilage degradation and joint inflammation. TGF-beta1 activates Akt, ERK and Smad2 pathways in chondrocytes. Here we investigated previously unexplored roles of specific Smads in TGF-beta1 induction of TIMP-3 gene by pharmacological and genetic knockdown approaches. TGF-beta1-induced Smad2 phosphorylation and TIMP-3 protein expression could be inhibited by the Smad2/3 phosphorylation inhibitors, PD169316 and SB203580 and by Smad2-specific siRNA. Specific inhibitor of Smad3 (SIS3) and Smad3 siRNA abolished TGF-beta induction of TIMP-3. Smad2/3 siRNAs also down regulated TIMP-3 promoter-driven luciferase activities, suggesting transcriptional regulation. SiRNA-driven co-Smad4 knockdown abrogated TIMP-3 augmentation by TGF-beta. TIMP-3 promoter deletion analysis revealed that -828 deletion retains the original promoter activity while -333 and -167 deletions display somewhat reduced activity suggesting that most of the TGF-beta-responsive, cis-acting elements are found in the -333 fragment. Chromatin Immunoprecipitation (ChIP) analysis confirmed binding of Smad2 and Smad4 with the -940 and -333 promoter sequences. These results suggest that receptor-activated Smad2 and Smad3 and co-Smad4 critically mediate TGF-beta-stimulated TIMP-3 expression in human chondrocytes and TIMP-3 gene is a target of Smad signaling pathway.

  7. Short-term vitamin E treatment impairs reactive oxygen species signaling required for adipose tissue expansion, resulting in fatty liver and insulin resistance in obese mice.

    Directory of Open Access Journals (Sweden)

    Martin Alcala

    Full Text Available The use of antioxidant therapy in the treatment of oxidative stress-related diseases such as cardiovascular disease, diabetes or obesity remains controversial. Our aim is to demonstrate that antioxidant supplementation may promote negative effects if used before the establishment of oxidative stress due to a reduced ROS generation under physiological levels, in a mice model of obesity.C57BL/6J mice were fed with a high-fat diet for 14 weeks, with (OE group or without (O group vitamin E supplementation.O mice developed a mild degree of obesity, which was not enough to induce metabolic alterations or oxidative stress. These animals exhibited a healthy expansion of retroperitoneal white adipose tissue (rpWAT and the liver showed no signs of lipotoxicity. Interestingly, despite achieving a similar body weight, OE mice were insulin resistant. In the rpWAT they presented a reduced generation of ROS, even below physiological levels (C: 1651.0 ± 212.0; O: 3113 ± 284.7; OE: 917.6 ±104.4 RFU/mg protein. C vs OE p< 0.01. ROS decay may impair their action as second messengers, which could account for the reduced adipocyte differentiation, lipid transport and adipogenesis compared to the O group. Together, these processes limited the expansion of this fat pad and as a consequence, lipid flux shifted towards the liver, causing steatosis and hepatomegaly, which may contribute to the marked insulin resistance.This study provides in vivo evidence for the role of ROS as second messengers in adipogenesis, lipid metabolism and insulin signaling. Reducing ROS generation below physiological levels when the oxidative process has not yet been established may be the cause of the controversial results obtained by antioxidant therapy.

  8. Biomedical Engineering Desk Reference

    CERN Document Server

    Ratner, Buddy D; Schoen, Frederick J; Lemons, Jack E; Dyro, Joseph; Martinsen, Orjan G; Kyle, Richard; Preim, Bernhard; Bartz, Dirk; Grimnes, Sverre; Vallero, Daniel; Semmlow, John; Murray, W Bosseau; Perez, Reinaldo; Bankman, Isaac; Dunn, Stanley; Ikada, Yoshito; Moghe, Prabhas V; Constantinides, Alkis

    2009-01-01

    A one-stop Desk Reference, for Biomedical Engineers involved in the ever expanding and very fast moving area; this is a book that will not gather dust on the shelf. It brings together the essential professional reference content from leading international contributors in the biomedical engineering field. Material covers a broad range of topics including: Biomechanics and Biomaterials; Tissue Engineering; and Biosignal Processing* A hard-working desk reference providing all the essential material needed by biomedical and clinical engineers on a day-to-day basis * Fundamentals, key techniques,

  9. [Reference citation].

    Science.gov (United States)

    Brkić, Silvija

    2013-01-01

    Scientific and professional papers represent the information basis for scientific research and professional work. References important for the paper should be cited within the text, and listed at the end of the paper. This paper deals with different styles of reference citation. Special emphasis was placed on the Vancouver Style for reference citation in biomedical journals established by the International Committee of Medical Journal Editors. It includes original samples for citing various types of articles, both printed and electronic, as well as recommendations related to reference citation in accordance with the methodology and ethics of scientific research and guidelines for preparing manuscripts for publication.

  10. Anal submucosal injection: a new route for drug administration in pelvic malignancies. Part I. Experimental study of misonidazole distribution in serum and tissues, with special reference to urinary bladder. Preliminary report

    International Nuclear Information System (INIS)

    Shafik, A.; el-Merzabani, M.M.; el-Aaser, A.A.; el-Desouky, G.H.

    1986-01-01

    The anal and oral administration routes were compared in 30 rats to study the distribution of misonidazole, a radiation sensitizer, in the serum and tissues with special reference to the urinary bladder. 14C-labelled misonidazole was administered in a dose of 0.2 ml water/100 gm body weight containing 1 mu Ci misonidazole. The dose was given orally by stomach tube in 15 rats, and was injected in the submucosa of the anal canal in another 15. Animals were then killed after 15, 30, 60, or 120 minutes or after 24 hours. Organs were dissected, and radioactivity was determined in each by the internal standard method. The study has shown that the highest drug concentration in the bladder tissue relative to the serum was achieved with the anal submucosal route. Its level was eight and five times that of the serum 15 and 30 minutes after administration, respectively, in contrast to the oral route in which the drug concentration was one-quarter and equal to the serum level at the same time intervals. The anal route would thus provide the adequate channel required for misonidazole to promote radiation responsiveness in bladder carcinoma

  11. MicroRNAs are suitable for assessment as biomarkers from formalin-fixed paraffin-embedded tissue, and miR-24 represents an appropriate reference microRNA for diffuse large B-cell lymphoma studies.

    Science.gov (United States)

    Culpin, Rachel Emily; Sieniawski, Michal; Proctor, Stephen John; Menon, Geetha; Mainou-Fowler, Tryfonia

    2013-03-01

    Tissue biopsy specimens in the form of formalin-fixed paraffin-embedded tissue (FFPET) represent a valuable resource for biomarker identification and validation. However, to date, they remain an underused asset due to uncertainty regarding RNA extraction and the reliability of downstream techniques, including quantitative RT-PCR. Recently, much interest has emerged in the study of microRNAs; small single-stranded RNAs with a role in transcriptional regulation, that are thought to be well preserved in FFPET. In this study, we show that microRNA expression is comparable between FFPET and matched fresh-frozen samples (miR-17-5p: p=0.01, miR-92: p=0.003), and demonstrate that no significant deterioration in expression occurs over prolonged FFPET storage (p=0.06). Furthermore, microRNA expression is equivalent dependant on RNA extraction method (p<0.001) or DNAse treatment of total RNA (p<0.001). Finally, we validate miR-24 as a suitable reference microRNA for diffuse large B-cell lymphoma (DLBCL) FFPET studies.

  12. Reference Assessment

    Science.gov (United States)

    Bivens-Tatum, Wayne

    2006-01-01

    This article presents interesting articles that explore several different areas of reference assessment, including practical case studies and theoretical articles that address a range of issues such as librarian behavior, patron satisfaction, virtual reference, or evaluation design. They include: (1) "Evaluating the Quality of a Chat Service"…

  13. Recent references

    International Nuclear Information System (INIS)

    Ramavataram, S.

    1991-01-01

    In support of a continuing program of systematic evaluation of nuclear structure data, the National Nuclear Data Center maintains a complete computer file of references to the nuclear physics literature. Each reference is tagged by a keyword string, which indicates the kinds of data contained in the article. This master file of Nuclear Structure References (NSR) contains complete keyword indexes to literature published since 1969, with partial indexing of older references. Any reader who finds errors in the keyword descriptions is urged to report them to the National Nuclear Data Center so that the master NSR file can be corrected. In 1966, the first collection of Recent References was published as a separate issue of Nuclear Data Sheets. Every four months since 1970, a similar indexed bibliography to new nuclear experiments has been prepared from additions to the NSR file and published. Beginning in 1978, Recent References was cumulated annually, with the third issue completely superseding the two issues previously published during a given year. Due to publication policy changes, cumulation of Recent Reference was discontinued in 1986. The volume and issue number of all the cumulative issues published to date are given. NNDC will continue to respond to individual requests for special bibliographies on nuclear physics topics, in addition to those easily obtained from Recent References. If the required information is available from the keyword string, a reference list can be prepared automatically from the computer files. This service can be provided on request, in exchange for the timely communication of new nuclear physics results (e.g., preprints). A current copy of the NSR file may also be obtained in a standard format on magnetic tape from NNDC. Requests for special searches of the NSR file may also be directed to the National Nuclear Data Center

  14. Detection of microRNAs in frozen tissue sections by fluorescence in situ hybridization using locked nucleic acid probes and tyramide signal amplification

    DEFF Research Database (Denmark)

    Silahtaroglu, Asli; Nolting, Dorrit; Andersen, Lars Dyrskjøt

    2007-01-01

    been shown to increase detection sensitivity in FISH, combining these techniques into one protocol significantly decreases the time needed for miRNA detection in cryosections, while simultaneously retaining high detection sensitivity. Starting with fixation of the tissue sections, this miRNA FISH...

  15. Soft tissue twisting injuries of the knee

    International Nuclear Information System (INIS)

    Magee, T.; Shapiro, M.

    2001-01-01

    Twisting injuries occur as a result of differential motion of different tissue types in injuries with some rotational force. These injuries are well described in brain injuries but, to our knowledge, have not been described in the musculoskeletal literature. We correlated the clinical examination and MR findings of 20 patients with twisting injuries of the soft tissues around the knee. Design and patients: We prospectively followed the clinical courses of 20 patients with knee injuries who had clinical histories and MR findings to suggest twisting injuries of the subcutaneous tissues. Patients with associated internal derangement of the knee (i.e., meniscal tears, ligamentous or bone injuries) were excluded from this study. MR findings to suggest twisting injuries included linear areas of abnormal dark signal on T1-weighted sequences and abnormal bright signal on T2-weighted or short tau inversion recovery (STIR) sequences and/or signal to suggest hemorrhage within the subcutaneous tissues. These MR criteria were adapted from those established for indirect musculotendinous junction injuries. Results: All 20 patients presented with considerable pain that suggested internal derangement on physical examination by the referring orthopedic surgeons. All presented with injuries associated with rotational force. The patients were placed on a course of protected weight-bearing of the affected extremity for 4 weeks. All patients had pain relief by clinical examination after this period of protected weight-bearing. Twisting injuries of the soft tissues can result in considerable pain that can be confused with internal derangement of the knee on physical examination. Soft tissue twisting injuries need to be recognized on MR examinations as they may be the cause of the patient's pain despite no MR evidence of internal derangement of the knee. The demonstration of soft tissue twisting injuries in a patient with severe knee pain but no documented internal derangement on MR

  16. The Spallation Neutron Source RF Reference System

    CERN Document Server

    Piller, Maurice; Crofford, Mark; Doolittle, Lawrence; Ma, Hengjie

    2005-01-01

    The Spallation Neutron Source (SNS) RF Reference System includes the master oscillator (MO), local oscillator(LO) distribution, and Reference RF distribution systems. Coherent low noise Reference RF signals provide the ability to control the phase relationships between the fields in the front-end and linear accelerator (linac) RF cavity structures. The SNS RF Reference System requirements, implementation details, and performance are discussed.

  17. Controlled drug release for tissue engineering.

    Science.gov (United States)

    Rambhia, Kunal J; Ma, Peter X

    2015-12-10

    Tissue engineering is often referred to as a three-pronged discipline, with each prong corresponding to 1) a 3D material matrix (scaffold), 2) drugs that act on molecular signaling, and 3) regenerative living cells. Herein we focus on reviewing advances in controlled release of drugs from tissue engineering platforms. This review addresses advances in hydrogels and porous scaffolds that are synthesized from natural materials and synthetic polymers for the purposes of controlled release in tissue engineering. We pay special attention to efforts to reduce the burst release effect and to provide sustained and long-term release. Finally, novel approaches to controlled release are described, including devices that allow for pulsatile and sequential delivery. In addition to recent advances, limitations of current approaches and areas of further research are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. CpG in Combination with an Inhibitor of Notch Signaling Suppresses Formalin-Inactivated Respiratory Syncytial Virus-Enhanced Airway Hyperresponsiveness and Inflammation by Inhibiting Th17 Memory Responses and Promoting Tissue-Resident Memory Cells in Lungs.

    Science.gov (United States)

    Zhang, Lei; Li, Hongyong; Hai, Yan; Yin, Wei; Li, Wenjian; Zheng, Boyang; Du, Xiaomin; Li, Na; Zhang, Zhengzheng; Deng, Yuqing; Zeng, Ruihong; Wei, Lin

    2017-05-15

    Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine-enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross talk between TLR and Notch signaling pathways results in fine-tuning of TLR-triggered innate inflammatory responses. We evaluated the impact of TLR and Notch signaling on ERD in a murine model by administering CpG, an agonist of TLR9, in combination with L685,458, an inhibitor of Notch signaling during FI-RSV immunization. Activation with CpG or deficiency of MyD88-dependent TLR signaling did not alleviate airway inflammation in FI-RSV-immunized mice. Activation or inhibition of Notch signaling with Dll4, one of the Notch ligands, or L685,458 did not suppress FI-RSV-enhanced airway inflammation either. However, the CpG together with L685,458 markedly inhibited FI-RSV-enhanced airway hyperresponsiveness, weight loss, and lung inflammation. Interestingly, CpG plus L685,458 completely inhibited FI-RSV-associated Th17 and Th17-associated proinflammatory chemokine responses in lungs following RSV challenge but not Th1 or Th2, memory responses. In addition, FI-RSV plus CpG plus L685,458 promoted protective CD8 + lung tissue-resident memory (TRM) cells. These results indicate that activation of TLR signaling combined with inhibition of Notch signaling prevent FI-RSV ERD, and the mechanism appears to involve suppressing proinflammatory Th17 memory responses and promoting protective TRM in lungs. IMPORTANCE RSV is the most important cause of lower respiratory tract infections in infants. The FI-RSV-enhanced respiratory disease (ERD) is a major impediment to the development of a safe and

  19. Reference Japanese man

    International Nuclear Information System (INIS)

    Tanaka, Giichiro

    1985-01-01

    To make real and accurate dose assessment method so far, it is necessitated to provide ''Reference Japanese Man'' based on anotomical, physiological and biochemical data of Japanese people instead of the Reference Man presented in ICRP Publications 23 and 30. This review describes present status of researched for the purpose of establishing of Reference Japanese Man. The Reference Japanese Man is defined as a male or female adult who lives in Japan with a Japanese life-style and food custom. His stature and body weight, and the other data was decided as mean values of male or female people of Japan. As for food custom, Japanese people take significantly smaller amount of meat and milk products than Western people, while larger intake amount of cereals and marine products such as fish or seaweeds. Weight of organs is a principal factor for internal dose assessment and mean values for living Japanese adult has been investigated and the value employable for dose assessment for organs and tissues are shown. To employ these values of Reference Japanese Man, it should be taken into account of age. Metabolic parameters should also be considered. Iodine metabolism in Japanese is quite different from that of Western people. The above-mentioned data are now tentatively employing in modification of table of MIRD method and others. (Takagi, S.)

  20. Quantitative analysis and comparison study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 using a reference tissue model.

    Directory of Open Access Journals (Sweden)

    Ning Guo

    Full Text Available With favorable pharmacokinetics and binding affinity for α(vβ(3 integrin, (18F-labeled dimeric cyclic RGD peptide ([(18F]FPPRGD2 has been intensively used as a PET imaging probe for lesion detection and therapy response monitoring. A recently introduced kit formulation method, which uses an (18F-fluoride-aluminum complex labeled RGD tracer ([(18F]AlF-NOTA-PRGD2, provides a strategy for simplifying the labeling procedure to facilitate clinical translation. Meanwhile, an easy-to-prepare (68Ga-labeled NOTA-PRGD2 has also been reported to have promising properties for imaging integrin α(vβ(3. The purpose of this study is to quantitatively compare the pharmacokinetic parameters of [(18F]FPPRGD2, [(18F]AlF-NOTA-PRGD2, and [(68Ga]Ga-NOTA-PRGD2. U87MG tumor-bearing mice underwent 60-min dynamic PET scans following the injection of three tracers. Kinetic parameters were calculated using Logan graphical analysis with reference tissue. Parametric maps were generated using voxel-level modeling. All three compounds showed high binding potential (Bp(ND = k(3/k(4 in tumor voxels. [(18F]AlF-NOTA-PRGD2 showed comparable Bp(ND value (3.75±0.65 with those of [(18F]FPPRGD2 (3.39±0.84 and [(68Ga]Ga-NOTA-PRGD2 (3.09±0.21 (p>0.05. Little difference was found in volume of distribution (V(T among these three RGD tracers in tumor, liver and muscle. Parametric maps showed similar kinetic parameters for all three tracers. We also demonstrated that the impact of non-specific binding could be eliminated in the kinetic analysis. Consequently, kinetic parameter estimation showed more comparable results among groups than static image analysis. In conclusion, [(18F]AlF-NOTA-PRGD2 and [(68Ga]Ga-NOTA-PRGD2 have comparable pharmacokinetics and quantitative parameters compared to those of [(18F]FPPRGD2. Despite the apparent difference in tumor uptake (%ID/g determined from static images and clearance pattern, the actual specific binding component extrapolated from kinetic

  1. Gene expression of tumour necrosis factor and insulin signalling-related factors in subcutaneous adipose tissue during the dry period and in early lactation in dairy cows.

    Science.gov (United States)

    Sadri, H; Bruckmaier, R M; Rahmani, H R; Ghorbani, G R; Morel, I; van Dorland, H A

    2010-10-01

    Gene expression of adipose factors, which may be part of the mechanisms that underlie insulin sensitivity, were studied in dairy cows around parturition. Subcutaneous fat biopsies and blood samples were taken from 27 dairy cows in week 8 antepartum (a.p.), on day 1 postpartum (p.p.) and in week 5 p.p. In the adipose tissue samples, mRNA was quantified by real-time reverse transcription polymerase chain reaction for tumour necrosis factor alpha (TNFα), insulin-independent glucose transporter (GLUT1), insulin-responsive glucose transporter (GLUT4), insulin receptor, insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), regulatory subunit of phosphatidylinositol-3 kinase (p85) and catalytic subunit of phosphatidylinositol-3 kinase. Blood plasma was assayed for concentrations of glucose, β-hydroxybutyric acid, non-esterified fatty acids (NEFA) and insulin. Plasma parameters followed a pattern typically observed in dairy cows. Gene expression changes were observed, but there were no changes in TNFα concentrations, which may indicate its local involvement in catabolic adaptation of adipose tissue. Changes in GLUT4 and GLUT1 mRNA abundance may reflect their involvement in reduced insulin sensitivity and in sparing glucose for milk synthesis in early lactation. Unchanged gene expression of IRS1, IRS2 and p85 over time may imply a lack of their involvement in terms of insulin sensitivity dynamics. Alternatively, it may indicate that post-transcriptional modifications of these factors came into play and may have concealed an involvement. © 2010 Blackwell Verlag GmbH.

  2. Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling

    Directory of Open Access Journals (Sweden)

    Moriyama Mariko

    2012-08-01

    Full Text Available Abstract Background Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12. Results We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO, resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2 and fibroblast growth factor 2 (FGF2 transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK. Conclusions Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson’s disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.

  3. Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet.

    Science.gov (United States)

    Bursać, Biljana; Djordjevic, Ana; Veličković, Nataša; Milutinović, Danijela Vojnović; Petrović, Snježana; Teofilović, Ana; Gligorovska, Ljupka; Preitner, Frederic; Tappy, Luc; Matić, Gordana

    2018-05-03

    Both fructose overconsumption and increased glucocorticoids secondary to chronic stress may contribute to overall dyslipidemia. In this study we specifically assessed the effects and interactions of dietary fructose and chronic stress on lipid metabolism in the visceral adipose tissue (VAT) of male Wistar rats. We analyzed the effects of 9-week 20% high fructose diet and 4-week chronic unpredictable stress, separately and in combination, on VAT histology, glucocorticoid prereceptor metabolism, glucocorticoid receptor subcellular redistribution and expression of major metabolic genes. Blood triglycerides and fatty acid composition were also measured to assess hepatic Δ9 desaturase activity. The results showed that fructose diet increased blood triglycerides and Δ9 desaturase activity. On the other hand, stress led to corticosterone elevation, glucocorticoid receptor activation and decrease in adipocyte size, while phosphoenolpyruvate carboxykinase, adipose tissue triglyceride lipase, FAT/CD36 and sterol regulatory element binding protein-1c (SREBP-1c) were increased, pointing to VAT lipolysis and glyceroneogenesis. The combination of stress and fructose diet was associated with marked stimulation of fatty acid synthase and acetyl-CoA carboxylase mRNA level and with increased 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase protein levels, suggesting a coordinated increase in hexose monophosphate shunt and de novo lipogenesis. It however did not influence the level of peroxisome proliferator-activated receptor-gamma, SREBP-1c and carbohydrate responsive element-binding protein. In conclusion, our results showed that only combination of dietary fructose and stress increase glucocorticoid prereceptor metabolism and stimulates lipogenic enzyme expression suggesting that interaction between stress and fructose may be instrumental in promoting VAT expansion and dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. System for tissue characterization using synchronous detection of diffuse reflectance

    International Nuclear Information System (INIS)

    Morales Lopez, Orestes M.; Stolik Isakina, Suren; La Rosa Vazquez, Jose Manuel de; Valor Reed, Alma

    2016-01-01

    The development of a system for the characterization of tissues optical properties in-vivo by synchronous detection of diffuse reflectance is presented. The system comprises an exploring probe with a linear spatial arrangement of optical fibers coupled to six lasers of 650 nm wavelength and a photodiode. The system also includes a preamplifier circuit for the photodiode, a driver for the amplitude modulation of the light signal of the lasers with optical power monitoring, a digital phase splitter for reference signal generation, an amplifying circuit with digitally switch able gain, a double phase demodulation circuit, an Arduino, and a control interface developed in LabVIEW. (Author)

  5. Exposure to carbon ions triggers pro-inflammatory signals, changes in homeostasis and epidermal tissue organization to a similar extent as photons

    Directory of Open Access Journals (Sweden)

    Palma eSimoniello

    2016-01-01

    Full Text Available The increasing application of charged particles in radiotherapy requires a deeper understanding of early and late side effects occurring in skin, which is exposed in all radiation treatments. We measured cellular and molecular changes related to the early inflammatory response of human skin irradiated with carbon ions, in particular cell death induction and changes in differentiation and proliferation of epidermal cells during the first days after exposure.Model systems for human skin from healthy donors of different complexity, i.e. keratinocytes, co-culture of skin cells, 3D skin equivalent and skin explants, were used to investigate the alterations induced by carbon ions (spread-out Bragg-peak, dose averaged LET 100 keV/µm in comparison to X-ray and UV-B exposure. After exposure to ionizing radiation, in none of the model systems apoptosis/necrosis was observed. Carbon ions triggered inflammatory signalling and accelerated differentiation of keratinocytes to a similar extent as X-rays at the same doses. High doses of carbon ions were more effective than X-rays in reducing proliferation and inducing abnormal differentiation. In contrast, changes identified following low dose exposure (≤ 0.5 Gy were induced more effectively after X-ray exposure, i.e. enhanced proliferation and change in the polarity of basal cells.

  6. Signal-to-noise ratio and MR tissue parameters in human brain imaging at 3, 7, and 9.4 tesla using current receive coil arrays.

    Science.gov (United States)

    Pohmann, Rolf; Speck, Oliver; Scheffler, Klaus

    2016-02-01

    Relaxation times, transmit homogeneity, signal-to-noise ratio (SNR) and parallel imaging g-factor were determined in the human brain at 3T, 7T, and 9.4T, using standard, tight-fitting coil arrays. The same human subjects were scanned at all three field strengths, using identical sequence parameters and similar 31- or 32-channel receive coil arrays. The SNR of three-dimensional (3D) gradient echo images was determined using a multiple replica approach and corrected with measured flip angle and T2 (*) distributions and the T1 of white matter to obtain the intrinsic SNR. The g-factor maps were derived from 3D gradient echo images with several GRAPPA accelerations. As expected, T1 values increased, T2 (*) decreased and the B1 -homogeneity deteriorated with increasing field. The SNR showed a distinctly supralinear increase with field strength by a factor of 3.10 ± 0.20 from 3T to 7T, and 1.76 ± 0.13 from 7T to 9.4T over the entire cerebrum. The g-factors did not show the expected decrease, indicating a dominating role of coil design. In standard experimental conditions, SNR increased supralinearly with field strength (SNR ∼ B0 (1.65) ). To take full advantage of this gain, the deteriorating B1 -homogeneity and the decreasing T2 (*) have to be overcome. © 2015 Wiley Periodicals, Inc.

  7. Japanese reference man 1988, 3

    International Nuclear Information System (INIS)

    Tanaka, Gi-ichiro

    1988-01-01

    Quantitative description of physical properties and other characteristics of the human body is one of the basic data for estimating dose equivalent and calculating Annual Limit on Intake of radionuclides. The exact mass weight of organs and tissues are measured from about 1000 autopsy cases of normal Japanese adults and physical properties are obtained from recent Japanese Government publications. Japanese (Asian) Reference Man is completed by establishing the Normal Japanese, harmonizing with Caucasian Reference Man and coinciding with the ICRP Reference Man Task Group members concept. (author)

  8. A tissue regeneration approach to bone and cartilage repair

    CERN Document Server

    Dunstan, Colin; Rosen, Vicki

    2015-01-01

    Reviewing exhaustively the current state of the art of tissue engineering strategies for regenerating bones and joints through the use of biomaterials, growth factors and stem cells, along with an investigation of the interactions between biomaterials, bone cells, growth factors and added stem cells and how together skeletal tissues can be optimised, this book serves to highlight the importance of biomaterials composition, surface topography, architectural and mechanical properties in providing support for tissue regeneration. Maximizing reader insights into the importance of the interplay of these attributes with bone cells (osteoblasts, osteocytes and osteoclasts) and cartilage cells (chondrocytes), this book also provides a detailed reference as to how key signalling pathways are activated. The contribution of growth factors to drive tissue regeneration and stem cell recruitment is discussed along with a review the potential and challenges of adult or embryonic mesenchymal stem cells to further enhance the...

  9. Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway

    Directory of Open Access Journals (Sweden)

    Freeman Robert S

    2011-02-01

    Full Text Available Abstract Background Thrombolytic therapy with tissue plasminogen activator (tPA benefits patients with acute ischemic stroke. However, tPA increases the risk for intracerebral bleeding and enhances post-ischemic neuronal injury if administered 3-4 hours after stroke. Therefore, combination therapies with tPA and neuroprotective agents have been considered to increase tPA's therapeutic window and reduce toxicity. The anticoagulant factor protein S (PS protects neurons from hypoxic/ischemic injury. PS also inhibits N-methyl-D-aspartate (NMDA excitotoxicity by phosphorylating Bad and Mdm2 which blocks the downstream steps in the intrinsic apoptotic cascade. To test whether PS can protect neurons from tPA toxicity we studied its effects on tPA/NMDA combined injury which in contrast to NMDA alone kills neurons by activating the extrinsic apoptotic pathway. Neither Bad nor Mdm2 which are PS's targets and control the intrinsic apoptotic pathway can influence the extrinsic cascade. Thus, based on published data one cannot predict whether PS can protect neurons from tPA/NMDA injury by blocking the extrinsic pathway. Neurons express all three TAM (Tyro3, Axl, Mer receptors that can potentially interact with PS. Therefore, we studied whether PS can activate TAM receptors during a tPA/NMDA insult. Results We show that PS protects neurons from tPA/NMDA-induced apoptosis by suppressing Fas-ligand (FasL production and FasL-dependent caspase-8 activation within the extrinsic apoptotic pathway. By transducing neurons with adenoviral vectors expressing the kinase-deficient Akt mutant AktK179A and a triple FKHRL1 Akt phosphorylation site mutant (FKHRL1-TM, we show that Akt activation and Akt-mediated phosphorylation of FKHRL1, a member of the Forkhead family of transcription factors, are critical for FasL down-regulation and caspase-8 inhibition. Using cultured neurons from Tyro3, Axl and Mer mutants, we show that Tyro3, but not Axl and Mer, mediates

  10. Estimation of ellagic acid and/or repaglinide effects on insulin signaling, oxidative stress, and inflammatory mediators of liver, pancreas, adipose tissue, and brain in insulin resistant/type 2 diabetic rats.

    Science.gov (United States)

    Amin, Mohamed M; Arbid, Mahmoud S

    2017-02-01

    Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks. At the serum level, ellagic acid challenged the consequences of HFFD, significantly improving the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adipokines, ammonia, and manganese. At the tissue level (liver, pancreas, adipose tissue, and brain), ellagic acid significantly enhanced insulin signaling, autophosphorylation, adiponectin receptors, glucose transporters, inflammatory mediators, and apoptotic markers. Remarkably, combined treatment with both ellagic acid and repaglinide had a more pronounced effect than treatment with either alone. These outcomes give new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.

  11. IL-4/5 signalling plays an important role during Litomosoides sigmodontis infection, influencing both immune system regulation and tissue pathology in the thoracic cavity.

    Science.gov (United States)

    Ritter, Manuel; Tamadaho, Ruth S; Feid, Judith; Vogel, Wenzel; Wiszniewsky, Katharina; Perner, Sven; Hoerauf, Achim; Layland, Laura E

    2017-12-01

    -/- mice. In summary, this study unravels the essential role of IL-4/IL-5 signalling in controlling immunity against filarial infections and demonstrates the requirement of this pathway for the host to control ensuing pathology and inflammation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Signal intensity of normal breast tissue at MR mammography on midfield: Applying a random coefficient model evaluating the effect of doubling the contrast dose

    Energy Technology Data Exchange (ETDEWEB)

    Marklund, Mette [Parker Institute: Imaging Unit, Frederiksberg Hospital (Denmark)], E-mail: mm@frh.regionh.dk; Christensen, Robin [Parker Institute: Musculoskeletal Statistics Unit, Frederiksberg Hospital (Denmark)], E-mail: robin.christensen@frh.regionh.dk; Torp-Pedersen, Soren [Parker Institute: Imaging Unit, Frederiksberg Hospital (Denmark)], E-mail: stp@frh.regionh.dk; Thomsen, Carsten [Department of Radiology, Rigshospitalet, University of Copenhagen (Denmark)], E-mail: carsten.thomsen@rh.regionh.dk; Nolsoe, Christian P. [Department of Radiology, Koge Hospital (Denmark)], E-mail: cnolsoe@dadlnet.dk

    2009-01-15

    Purpose: To prospectively investigate the effect on signal intensity (SI) of healthy breast parenchyma on magnetic resonance mammography (MRM) when doubling the contrast dose from 0.1 to 0.2 mmol/kg bodyweight. Materials and methods: Informed consent and institutional review board approval were obtained. Twenty-five healthy female volunteers (median age: 24 years (range: 21-37 years) and median bodyweight: 65 kg (51-80 kg)) completed two dynamic MRM examinations on a 0.6 T open scanner. The inter-examination time was 24 h (23.5-25 h). The following sequences were applied: axial T2W TSE and an axial dynamic T1W FFED, with a total of seven frames. At day 1, an i.v. gadolinium (Gd) bolus injection of 0.1 mmol/kg bodyweight (Omniscan) (low) was administered. On day 2, the contrast dose was increased to 0.2 mmol/kg (high). Injection rate was 2 mL/s (day 1) and 4 mL/s (day 2). Any use of estrogen containing oral contraceptives (ECOC) was recorded. Post-processing with automated subtraction, manually traced ROI (region of interest) and recording of the SI was performed. A random coefficient model was applied. Results: We found an SI increase of 24.2% and 40% following the low and high dose, respectively (P < 0.0001); corresponding to a 65% (95% CI: 37-99%) SI increase, indicating a moderate saturation. Although not statistically significant (P = 0.06), the results indicated a tendency, towards lower maximal SI in the breast parenchyma of ECOC users compared to non-ECOC users. Conclusion: We conclude that the contrast dose can be increased from 0.1 to 0.2 mmol/kg bodyweight, if a better contrast/noise relation is desired but increasing the contrast dose above 0.2 mmol/kg bodyweight is not likely to improve the enhancement substantially due to the moderate saturation observed. Further research is needed to determine the impact of ECOC on the relative enhancement ratio, and further studies are needed to determine if a possible use of ECOC should be considered a compromising

  13. Signal intensity of normal breast tissue at MR mammography on midfield: Applying a random coefficient model evaluating the effect of doubling the contrast dose

    International Nuclear Information System (INIS)

    Marklund, Mette; Christensen, Robin; Torp-Pedersen, Soren; Thomsen, Carsten; Nolsoe, Christian P.

    2009-01-01

    Purpose: To prospectively investigate the effect on signal intensity (SI) of healthy breast parenchyma on magnetic resonance mammography (MRM) when doubling the contrast dose from 0.1 to 0.2 mmol/kg bodyweight. Materials and methods: Informed consent and institutional review board approval were obtained. Twenty-five healthy female volunteers (median age: 24 years (range: 21-37 years) and median bodyweight: 65 kg (51-80 kg)) completed two dynamic MRM examinations on a 0.6 T open scanner. The inter-examination time was 24 h (23.5-25 h). The following sequences were applied: axial T2W TSE and an axial dynamic T1W FFED, with a total of seven frames. At day 1, an i.v. gadolinium (Gd) bolus injection of 0.1 mmol/kg bodyweight (Omniscan) (low) was administered. On day 2, the contrast dose was increased to 0.2 mmol/kg (high). Injection rate was 2 mL/s (day 1) and 4 mL/s (day 2). Any use of estrogen containing oral contraceptives (ECOC) was recorded. Post-processing with automated subtraction, manually traced ROI (region of interest) and recording of the SI was performed. A random coefficient model was applied. Results: We found an SI increase of 24.2% and 40% following the low and high dose, respectively (P < 0.0001); corresponding to a 65% (95% CI: 37-99%) SI increase, indicating a moderate saturation. Although not statistically significant (P = 0.06), the results indicated a tendency, towards lower maximal SI in the breast parenchyma of ECOC users compared to non-ECOC users. Conclusion: We conclude that the contrast dose can be increased from 0.1 to 0.2 mmol/kg bodyweight, if a better contrast/noise relation is desired but increasing the contrast dose above 0.2 mmol/kg bodyweight is not likely to improve the enhancement substantially due to the moderate saturation observed. Further research is needed to determine the impact of ECOC on the relative enhancement ratio, and further studies are needed to determine if a possible use of ECOC should be considered a compromising

  14. Reference in human and non-human primate communication: What does it take to refer?

    Science.gov (United States)

    Sievers, Christine; Gruber, Thibaud

    2016-07-01

    The concept of functional reference has been used to isolate potentially referential vocal signals in animal communication. However, its relatedness to the phenomenon of reference in human language has recently been brought into question. While some researchers have suggested abandoning the concept of functional reference altogether, others advocate a revision of its definition to include contextual cues that play a role in signal production and perception. Empirical and theoretical work on functional reference has also put much emphasis on how the receiver understands the referential signal. However, reference, as defined in the linguistic literature, is an action of the producer, and therefore, any definition describing reference in non-human animals must also focus on the producer. To successfully determine whether a signal is used to refer, we suggest an approach from the field of pragmatics, taking a closer look at specific situations of signal production, specifically at the factors that influence the production of a signal by an individual. We define the concept of signaller's reference to identify intentional acts of reference produced by a signaller independently of the communicative modality, and illustrate it with a case study of the hoo vocalizations produced by wild chimpanzees during travel. This novel framework introduces an intentional approach to referentiality. It may therefore permit a closer comparison of human and non-human animal referential behaviour and underlying cognitive processes, allowing us to identify what may have emerged solely in the human lineage.

  15. Engineering Musculoskeletal Tissue Interfaces

    Directory of Open Access Journals (Sweden)

    Ece Bayrak

    2018-04-01

    Full Text Available Tissue engineering aims to bring together biomaterials, cells, and signaling molecules within properly designed microenvironments in order to create viable treatment options for the lost or malfunctioning tissues. Design and production of scaffolds and cell-laden grafts that mimic the complex structural and functional features of tissues are among the most important elements of tissue engineering strategy. Although all tissues have their own complex structure, an even more complex case in terms of engineering a proper carrier material is encountered at the tissue interfaces, where two distinct tissues come together. The interfaces in the body can be examined in four categories; cartilage-bone and ligament-bone interfaces at the knee and the spine, tendon-bone interfaces at the shoulder and the feet, and muscle-tendon interface at the skeletal system. These interfaces are seen mainly at the soft-to-hard tissue transitions and they are especially susceptible to injury and tear due to the biomechanical inconsistency between these tissues where high strain fields are present. Therefore, engineering the musculoskeletal tissue interfaces remain a challenge. This review focuses on recent advancements in strategies for musculoskeletal interface engineering using different biomaterial-based platforms and surface modification techniques.

  16. Universal Reference RNA as a standard for microarray experiments

    Directory of Open Access Journals (Sweden)

    Fero Michael

    2004-03-01

    Full Text Available Abstract Background Obtaining reliable and reproducible two-color microarray gene expression data is critically important for understanding the biological significance of perturbations made on a cellular system. Microarray design, RNA preparation and labeling, hybridization conditions and data acquisition and analysis are variables difficult to simultaneously control. A useful tool for monitoring and controlling intra- and inter-experimental variation is Universal Reference RNA (URR, developed with the goal of providing hybridization signal at each microarray probe location (spot. Measuring signal at each spot as the ratio of experimental RNA to reference RNA targets, rather than relying on absolute signal intensity, decreases variability by normalizing signal output in any two-color hybridization experiment. Results Human, mouse and rat URR (UHRR, UMRR and URRR, respectively were prepared from pools of RNA derived from individual cell lines representing different tissues. A variety of microarrays were used to determine percentage of spots hybridizing with URR and producing signal above a user defined threshold (microarray coverage. Microarray coverage was consistently greater than 80% for all arrays tested. We confirmed that individual cell lines contribute their own unique set of genes to URR, arguing for a pool of RNA from several cell lines as a better configuration for URR as opposed to a single cell line source for URR. Microarray coverage comparing two separately prepared batches each of UHRR, UMRR and URRR were highly correlated (Pearson's correlation coefficients of 0.97. Conclusion Results of this study demonstrate that large quantities of pooled RNA from individual cell lines are reproducibly prepared and possess diverse gene representation. This type of reference provides a standard for reducing variation in microarray experiments and allows more reliable comparison of gene expression data within and between experiments and

  17. Intracranial CSF flow on cine-MR. 2. Qualitative analysis in CSF dynamics by MR signal ratio of CSF to fat tissue in healthy subjects and patients with aqueduct stenosis

    International Nuclear Information System (INIS)

    Kadowaki, Chikafusa; Hara, Mitsuhiro; Takeuchi, Kazuo; Saito, Isamu

    1994-01-01

    Changes in MR signal intensities (SIs) of CSF and relative MR signal ratios (SRs) of intraventricular CSF to fat tissue were evaluated in 5 healthy adults on cine MR images during a cardiac cycle in a study of normal intracranial CSF dynamics. The altered patterns of MR SIs and SRs in 6 patients with aqueduct stenosis were compared with normal CSF flow patterns in a demonstration of CSF dynamics changes. MR SIs of CSF within the ventricles were measured on each cine image obtained by cardiac gated, multiframe, cine MR imaging. Chronological changes in MR SIs and SRs during a cardiac cycle were compared with the actual CSF flow visualized on real cine images. In normal CSF circulation, MR SIs of CSF within the ventricles were reduced quickly following an R-wave on ECG to 15% of the R-R interval, after which SIs fluctuated slightly. These changes in MR SIs of CSF could only be related to the pulsatile CSF flow through the foramen of Monro into the anterior part of the third ventricle during early cardiac systole. MR SRs of CSF to fat tissue fluctuated according to the actual CSF flow within the ventricles during a cardiac cycle. MR SRs in the third ventricle decreased to 20-30% of the R-R interval following the R-wave due to downward CSF flow during early cardiac systole, and decreased again from late cardiac systole to diastole due to caudal CSF flow in the third ventricle. In the fourth ventricle, MR SRs of CSF decreased to 60-80% of the R-R interval because of the CSF flow through the aqueduct during cardiac diastole. In patients with aqueduct stenosis, MR SRs of CSF within the ventricles fluctuated randomly, and the amplitude of MR SRs was also greater than in subjects with a patent aqueduct. These changes were identified as turbulence and stagnation due to obstruction in the CSF pathway. Analysis of chronological changes in MR signal ratios of CSF to fat is useful in demonstrating the pathophysiologic features of intracranial CSF dynamics. (author) 52 refs

  18. Synthetic Phage for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2014-01-01

    Full Text Available Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy.

  19. Enhancement of osteogenic differentiation of rat adipose tissue-derived mesenchymal stem cells by zinc sulphate under electromagnetic field via the PKA, ERK1/2 and Wnt/β-catenin signaling pathways.

    Directory of Open Access Journals (Sweden)

    Ezzatollah Fathi

    Full Text Available Zinc ion as an essential trace element and electromagnetic fields (EMFs has been reported to be involved in the regulation of bone metabolism. The aim of this study was to elucidate the effects of zinc sulphate (ZnSO4 on the osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ADSCs in the presence of EMF as a strategy in osteoporosis therapy. Alkaline phophatase (ALP activity measurement, calcium assay and expression of several osteoblastic marker genes were examined to assess the effect of ZnSO4 on the osteogenic differentiation of ADSCs under EMF. The expression of cAMP and PKA was evaluated by ELISA. The expression of β-catenin, Wnt1, Wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5 and reduced dickkopf1 (DKK1 genes were used to detect the Wnt/β-catenin pathway. It was found that ZnSO4, in the presence of EMF, resulted in an increase in the expression of osteogenic genes, ALP activity and calcium levels. EMF, in the presence of ZnSO4, increased the cAMP level and protein kinase A (PKA activity. Treatment of ADSCs with (MAPK/ERK kinase 1/2 inhibitor, or PKA inhibitor, significantly inhibited the promotion of osteogenic markers, indicating that the induction of osteogenesis was dependent on the ERK and PKA signaling pathways. Real-time PCR analysis showed that ZnSO4, in the presence of EMF, increased the mRNA expressions of β-catenin, Wnt1, Wnt3a, LRP5 and DKK1. In this study, it was shown that 0.432 μg/ml ZnSO4, in the presence of 50 Hz, 20 mT EMF, induced the osteogenic differentiation of ADSCs via PKA, ERK1/2 and Wnt/β-catenin signaling pathways.

  20. Digital signal processing

    CERN Document Server

    O'Shea, Peter; Hussain, Zahir M

    2011-01-01

    In three parts, this book contributes to the advancement of engineering education and that serves as a general reference on digital signal processing. Part I presents the basics of analog and digital signals and systems in the time and frequency domain. It covers the core topics: convolution, transforms, filters, and random signal analysis. It also treats important applications including signal detection in noise, radar range estimation for airborne targets, binary communication systems, channel estimation, banking and financial applications, and audio effects production. Part II considers sel

  1. Adaptive Control with Reference Model Modification

    Science.gov (United States)

    Stepanyan, Vahram; Krishnakumar, Kalmanje

    2012-01-01

    This paper presents a modification of the conventional model reference adaptive control (MRAC) architecture in order to improve transient performance of the input and output signals of uncertain systems. A simple modification of the reference model is proposed by feeding back the tracking error signal. It is shown that the proposed approach guarantees tracking of the given reference command and the reference control signal (one that would be designed if the system were known) not only asymptotically but also in transient. Moreover, it prevents generation of high frequency oscillations, which are unavoidable in conventional MRAC systems for large adaptation rates. The provided design guideline makes it possible to track a reference commands of any magnitude from any initial position without re-tuning. The benefits of the method are demonstrated with a simulation example

  2. Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

    Science.gov (United States)

    Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

    2016-03-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF-dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antagonist) reduced TF release from macrophages stimulated with SP. Pretreatment of macrophages with a radical scavenger(pyrrolidinedithiocarbamate) also limited the decrease of TF in whole-cell lysates after stimulation with SP. A protein kinase C inhibitor (rottlerin) partially blocked this macrophage response to SP, while it was significantly inhibited by a ROCK inhibitor (Y-27632) or a dynamin inhibitor (dinasore). An Akt inhibitor (perifosine) also partially blocked this response. Furthermore, siRNA targeting p22phox, β-arrestin 2, or Rho A, blunted the release of TF from macrophages stimulated with SP. In other experiments, visceral adipocytes derived from cryopreserved preadipocytes were found to produce SP. In conclusion, SP enhances the release of TF from macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Nelumbo nucifera Gaertn leaves extract inhibits the angiogenesis and metastasis of breast cancer cells by downregulation connective tissue growth factor (CTGF) mediated PI3K/AKT/ERK signaling.

    Science.gov (United States)

    Chang, Chun-Hua; Ou, Ting-Tsz; Yang, Mon-Yuan; Huang, Chi-Chou; Wang, Chau-Jong

    2016-07-21

    Nelumbo nucifera Gaertn (Nymphaeaceae) has been recognized as a medicinal plant, which was distributed throughout the Asia. The aqueous extract of Nelumbo nucifera leaves extract (NLE) has various biologically active components such as polyphenols, flavonoids, oligomeric procyanidines. However, the role of NLE in breast cancer therapy is poorly understood. The purpose of this study was to identify the hypothesis that NLE can suppress tumor angiogenesis and metastasis through CTGF (connective tissue growth factor), which has been implicated in tumor angiogenesis and progression in breast cancer MDA-MB-231 cells. We examined the effects of NLE on angiogenesis in the chicken chorioallantoic membrane (CAM) model. The data showed that NLE could reduce the chorionic plexus at day 17 in CAM and the duration of this inhibition was dose-dependent. In Xenograft model, NLE treatment significantly reduced tumor weight and CD31 (capillary density) over control, respectively. We examined the role of angiogenesis involved restructuring of endothelium using human umbilical vein endothelial cell (HUVEC) in Matrigel angiogenesis model. The results indicated that vascular-like structure formation was further blocked by NLE treatment. Moreover, knockdown of CTGF expression markedly reduced the expression of MMP2 as well as VEGF, and attenuated PI3K-AKT-ERK activation, indication that these signaling pathways are crucial in mediating CTGF function. The present results suggest that NLE might be useful for treatment in therapy-resistance triple negative breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. rf reference line for PEP

    International Nuclear Information System (INIS)

    Schwarz, H.D.; Weaver, J.N.

    1979-03-01

    A rf phase reference line in 6 segments around the 2200 meter circumference PEP storage ring is described. Each segment of the reference line is phase stabilized by its own independent feedback system, which uses an amplitude modulated reflection from the end of each line. The modulation is kept small and decoupled from the next segment to avoid crosstalk and significant modulation of the rf drive signal. An error evaluation of the system is made. The technical implementation and prototype performance are described. Prototype tests indicate that the phase error around the ring can be held below 1 degree with this relatively simple system

  5. rf reference line for PEP

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, H.D.; Weaver, J.N.

    1979-03-01

    A rf phase reference line in 6 segments around the 2200 meter circumference PEP storage ring is described. Each segment of the reference line is phase stabilized by its own independent feedback system, which uses an amplitude modulated reflection from the end of each line. The modulation is kept small and decoupled from the next segment to avoid crosstalk and significant modulation of the rf drive signal. An error evaluation of the system is made. The technical implementation and prototype performance are described. Prototype tests indicate that the phase error around the ring can be held below 1 degree with this relatively simple system.

  6. Tissue engineering

    CERN Document Server

    Fisher, John P; Bronzino, Joseph D

    2007-01-01

    Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

  7. Signal Words

    Science.gov (United States)

    SIGNAL WORDS TOPIC FACT SHEET NPIC fact sheets are designed to answer questions that are commonly asked by the ... making decisions about pesticide use. What are Signal Words? Signal words are found on pesticide product labels, ...

  8. Jiang Tang Xiao Ke Granule Play an Anti-diabetic Role in Diabetic Mice Pancreatic Tissue by Regulating the mRNAs and MicroRNAs Associated with PI3K-Akt Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Fang-Fang Mo

    2017-11-01

    Full Text Available Purpose: To investigate the effect of JTXK granule on the expression pattern of miRNA in pancreatic tissue of KKAy diabetic mice, and to explore the molecular mechanism and pathways of JTXK granule in anti-diabetic effect.Methods: We used high fat diet (HFD to induce the KKAy diabetic mice and screened the differentially expressed miRNAs (DEMs between JTXK-treated group (n = 6 and the diabetic group (n = 6 using MicroRNA (miRNA Microarray. C57BL/6J mice were given a normal diet as the control group (n = 6. Subsequently, miRNA target gene prediction, GO and Pathway analysis were used to explore the function of DEMs. Finally, the mechanism of anti-diabetic effects of JTXK granule was tested by in vitro INS-1 pancreatic β-cell experiment.Results: The blood glucose and body weight of JTXK-treated group was significantly lower compared with the model group. Moreover, a total of 45 miRNAs with significant differences were detected in the model group and the JTXK-treated group (P ≤ 0.05, Fold Change > 2. Further, miRNA-mRNA analysis showed that the differential expression of mmu-miR-192-5p, mmu-miR-291a-3p, mmu-miR-320-3p, mmu-miR-139-5p and mmu-miR-378a-3p are closely related to pancreatic histological changes. In addition, pathway analysis showed that the DEMs were closely related to PI3K-Akt Signaling Pathway. Furthermore, the levels of serine/threonine-protein kinase (Akt, phosphorylated Akt (p-Akt and phosphorylated forkhead transcription factor O1 (p-Foxo1 in INS-1-FOXO1 overexpressing model cells were lower than those in normal group, while JTXK granules could increase the expression of Akt, p-Akt and p-Foxo1.Conclusions: The results showed that JTXK granule could play an anti-diabetic role by regulating the mRNA and miRNAs associated with PI3K-Akt pathway in diabetic mice pancreatic tissue.

  9. PuF, an antimetastatic and developmental signaling protein, interacts with the Alzheimer’s amyloid-β precursor protein via a tissue-specific proximal regulatory element (PRE

    Directory of Open Access Journals (Sweden)

    Lahiri Debomoy K

    2013-01-01

    Full Text Available Abstract Background Alzheimer’s disease (AD is intimately tied to amyloid-β (Aβ peptide. Extraneuronal brain plaques consisting primarily of Aβ aggregates are a hallmark of AD. Intraneuronal Aβ subunits are strongly implicated in disease progression. Protein sequence mutations of the Aβ precursor protein (APP account for a small proportion of AD cases, suggesting that regulation of the associated gene (APP may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or “proximal regulatory element” (PRE, at −76/−47, from the +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay (EMSA and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. Results EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 (AP2, nm23 nucleoside diphosphate kinase/metastatic inhibitory protein (PuF, and specificity protein 1 (SP1. These sites crossed a known single nucleotide polymorphism (SNP. EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. Conclusions We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also

  10. Tissue types (image)

    Science.gov (United States)

    ... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

  11. Standard Reference Tables -

    Data.gov (United States)

    Department of Transportation — The Standard Reference Tables (SRT) provide consistent reference data for the various applications that support Flight Standards Service (AFS) business processes and...

  12. Orexin/Hypocretin Signaling.

    Science.gov (United States)

    Kukkonen, Jyrki P

    Orexin/hypocretin peptide (orexin-A and orexin-B) signaling is believed to take place via the two G-protein-coupled receptors (GPCRs), named OX 1 and OX 2 orexin receptors, as described in the previous chapters. Signaling of orexin peptides has been investigated in diverse endogenously orexin receptor-expressing cells - mainly neurons but also other types of cells - and in recombinant cells expressing the receptors in a heterologous manner. Findings in the different systems are partially convergent but also indicate cellular background-specific signaling. The general picture suggests an inherently high degree of diversity in orexin receptor signaling.In the current chapter, I present orexin signaling on the cellular and molecular levels. Discussion of the connection to (potential) physiological orexin responses is only brief since these are in focus of other chapters in this book. The same goes for the post-synaptic signaling mechanisms, which are dealt with in Burdakov: Postsynaptic actions of orexin. The current chapter is organized according to the tissue type, starting from the central nervous system. Finally, receptor signaling pathways are discussed across tissues, cell types, and even species.

  13. Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 Positively Modulates Matrix Metalloproteinase-9 Production in Alveolar Macrophages upon Toll-Like Receptor 7 Signaling and Influenza Virus Infection

    Directory of Open Access Journals (Sweden)

    Yu-Hsiang Lee

    2017-09-01

    Full Text Available Influenza A virus (IAV infection causes significant morbidity and mortality worldwide. Matrix metalloproteinase-9 (MMP-9 degrades extracellular matrix and is involved in the pathology of influenza. It has been reported that MMP-9 mediates neutrophil migration in IAV infection. Whether alveolar macrophages, the first immune cells that encounter IAV, produce MMP-9, and the mechanism of its regulation have never been investigated. As Toll-like receptor 7 (TLR7 is one of the receptors in innate immune cells that recognize IAV, we used TLR7 agonists and IAV to stimulate alveolar macrophage MH-S cells, primary macrophages, and bone marrow neutrophils. Results showed that MMP-9 expression in macrophages is inducible by TLR7 agonists and IAV, yet, MMP-9 production by neutrophils is not inducible by either one of them. We hypothesized that MMP-9 production in macrophages is mediated through TLR7-NF-κB pathway and used microarray to analyze TLR7 agonist-induced NF-κB-related genes. Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1, a positive regulator of NF-κB, is amongst the top highly induced genes. By use of MALT1 inhibitor (z-VRPR-fmk and alveolar macrophages from MALT1-deficient mice, we found that MMP-9 production is MALT1-dependent. While MALT1 can act as a paracaspase in lymphocytes through degrading various signaling proteins, we discovered that MALT1 functions to reduce a negative regulator of NF-κB, cylindromatosis (CYLD, in alveolar macrophages. IAV-induced MMP-9, TNF, and IL-6 in lungs of MALT1-deficient mice are significantly lower than in wild-type mice after intratracheal infection. MALT1-deficient mice also have less body weight loss and longer survival after infection. Taken together, we demonstrated a novel role of MALT1 in regulating alveolar macrophage MMP-9 production whose presence exacerbates the severity of influenza.

  14. Bioelectric Signal Measuring System

    Science.gov (United States)

    Guadarrama-Santana, A.; Pólo-Parada, L.; García-Valenzuela, A.

    2015-01-01

    We describe a low noise measuring system based on interdigitated electrodes for sensing bioelectrical signals. The system registers differential voltage measurements in order of microvolts. The base noise during measurements was in nanovolts and thus, the sensing signals presented a very good signal to noise ratio. An excitation voltage of 1Vrms with 10 KHz frequency was applied to an interdigitated capacitive sensor without a material under test and to a mirror device simultaneously. The output signals of both devices was then subtracted in order to obtain an initial reference value near cero volts and reduce parasitic capacitances due to the electronics, wiring and system hardware as well. The response of the measuring system was characterized by monitoring temporal bioelectrical signals in real time of biological materials such as embryo chicken heart cells and bovine suprarenal gland cells.

  15. Optimal Signal Quality Index for Photoplethysmogram Signals

    Directory of Open Access Journals (Sweden)

    Mohamed Elgendi

    2016-09-01

    Full Text Available A photoplethysmogram (PPG is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is typically collected by pulse oximeters. PPG signals collected via mobile devices are prone to artifacts that negatively impact measurement accuracy, which can lead to a significant number of misleading diagnoses. Given the rapidly increased use of mobile devices to collect PPG signals, developing an optimal signal quality index (SQI is essential to classify the signal quality from these devices. Eight SQIs were developed and tested based on: perfusion, kurtosis, skewness, relative power, non-stationarity, zero crossing, entropy, and the matching of systolic wave detectors. Two independent annotators annotated all PPG data (106 recordings, 60 s each and a third expert conducted the adjudication of differences. The independent annotators labeled each PPG signal with one of the following labels: excellent, acceptable or unfit for diagnosis. All indices were compared using Mahalanobis distance, linear discriminant analysis, quadratic discriminant analysis, and support vector machine with leave-one-out cross-validation. The skewness index outperformed the other seven indices in differentiating between excellent PPG and acceptable, acceptable combined with unfit, and unfit recordings, with overall F 1 scores of 86.0%, 87.2%, and 79.1%, respectively.

  16. Optimal Signal Quality Index for Photoplethysmogram Signals.

    Science.gov (United States)

    Elgendi, Mohamed

    2016-09-22

    A photoplethysmogram (PPG) is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is typically collected by pulse oximeters. PPG signals collected via mobile devices are prone to artifacts that negatively impact measurement accuracy, which can lead to a significant number of misleading diagnoses. Given the rapidly increased use of mobile devices to collect PPG signals, developing an optimal signal quality index (SQI) is essential to classify the signal quality from these devices. Eight SQIs were developed and tested based on: perfusion, kurtosis, skewness, relative power, non-stationarity, zero crossing, entropy, and the matching of systolic wave detectors. Two independent annotators annotated all PPG data (106 recordings, 60 s each) and a third expert conducted the adjudication of differences. The independent annotators labeled each PPG signal with one of the following labels: excellent, acceptable or unfit for diagnosis. All indices were compared using Mahalanobis distance, linear discriminant analysis, quadratic discriminant analysis, and support vector machine with leave-one-out cross-validation. The skewness index outperformed the other seven indices in differentiating between excellent PPG and acceptable, acceptable combined with unfit, and unfit recordings, with overall F 1 scores of 86.0%, 87.2%, and 79.1%, respectively.

  17. Tissue Classification

    DEFF Research Database (Denmark)

    Van Leemput, Koen; Puonti, Oula

    2015-01-01

    Computational methods for automatically segmenting magnetic resonance images of the brain have seen tremendous advances in recent years. So-called tissue classification techniques, aimed at extracting the three main brain tissue classes (white matter, gray matter, and cerebrospinal fluid), are now...... well established. In their simplest form, these methods classify voxels independently based on their intensity alone, although much more sophisticated models are typically used in practice. This article aims to give an overview of often-used computational techniques for brain tissue classification...

  18. UWB pulse propagation into human tissues

    International Nuclear Information System (INIS)

    Cavagnaro, Marta; Pittella, Erika; Pisa, Stefano

    2013-01-01

    In this paper the propagation of a UWB pulse into a layered model of the human body is studied to characterize absorption and reflection of the UWB signal due to the different body tissues. Several time behaviours for the incident UWB pulse are considered and compared with reference to the feasibility of breath and heartbeat activity monitoring. Results show that if the UWB source is placed far from the human body, the reflection coming from the interface between air and skin can be used to detect the respiratory activity. On the contrary, if the UWB source is placed close to the human body, a small reflection due to the interface between the posterior lung wall and the bone, which is well distanced in time from the reflections due to the first layers of the body model, can be used to detect lung and heart changes associated with the cardio-respiratory activity. (paper)

  19. Soft tissue modelling with conical springs.

    Science.gov (United States)

    Omar, Nadzeri; Zhong, Yongmin; Jazar, Reza N; Subic, Aleksandar; Smith, Julian; Shirinzadeh, Bijan

    2015-01-01

    This paper presents a new method for real-time modelling soft tissue deformation. It improves the traditional mass-spring model with conical springs to deal with nonlinear mechanical behaviours of soft tissues. A conical spring model is developed to predict soft tissue deformation with reference to deformation patterns. The model parameters are formulated according to tissue deformation patterns and the nonlinear behaviours of soft tissues are modelled with the stiffness variation of conical spring. Experimental results show that the proposed method can describe different tissue deformation patterns using one single equation and also exhibit the typical mechanical behaviours of soft tissues.

  20. Hippo signalling directs intestinal fate

    DEFF Research Database (Denmark)

    le Bouteiller, Marie Catherine M; Jensen, Kim Bak

    2015-01-01

    Hippo signalling has been associated with many important tissue functions including the regulation of organ size. In the intestinal epithelium differing functions have been proposed for the effectors of Hippo signalling, YAP and TAZ1. These are now shown to have a dual role in the intestinal...

  1. 2002 reference document; Document de reference 2002

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-01

    This 2002 reference document of the group Areva, provides information on the society. Organized in seven chapters, it presents the persons responsible for the reference document and for auditing the financial statements, information pertaining to the transaction, general information on the company and share capital, information on company operation, changes and future prospects, assets, financial position, financial performance, information on company management and executive board and supervisory board, recent developments and future prospects. (A.L.B.)

  2. ATP signals

    DEFF Research Database (Denmark)

    Novak, Ivana

    2016-01-01

    The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas......The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas...

  3. Computational Modeling in Tissue Engineering

    CERN Document Server

    2013-01-01

    One of the major challenges in tissue engineering is the translation of biological knowledge on complex cell and tissue behavior into a predictive and robust engineering process. Mastering this complexity is an essential step towards clinical applications of tissue engineering. This volume discusses computational modeling tools that allow studying the biological complexity in a more quantitative way. More specifically, computational tools can help in:  (i) quantifying and optimizing the tissue engineering product, e.g. by adapting scaffold design to optimize micro-environmental signals or by adapting selection criteria to improve homogeneity of the selected cell population; (ii) quantifying and optimizing the tissue engineering process, e.g. by adapting bioreactor design to improve quality and quantity of the final product; and (iii) assessing the influence of the in vivo environment on the behavior of the tissue engineering product, e.g. by investigating vascular ingrowth. The book presents examples of each...

  4. Biological reference materials and analysis of toxic elements

    Energy Technology Data Exchange (ETDEWEB)

    Subramanian, R; Sukumar, A

    1988-12-01

    Biological monitoring of toxic metal pollution in the environment requires quality control analysis with use of standard reference materials. A variety of biological tissues are increasingly used for analysis of element bioaccumulation, but the available Certified Reference Materials (CRMs) are insufficient. An attempt is made to review the studies made using biological reference materials for animal and human tissues. The need to have inter-laboratory studies and CRM in the field of biological monitoring of toxic metals is also discussed.

  5. Development of beta reference radiations

    International Nuclear Information System (INIS)

    Wan Zhaoyong; Cai Shanyu; Li Yanbo; Yin Wei; Feng Jiamin; Sun Yuhua; Li Yongqiang

    1997-09-01

    A system of beta reference radiation has been developed, that is composed of 740 MBq 147 Pm beta source, 74 MBq and 740 MBq 90 Sr + 90 Y β sources, compensation filters, a source handling tool, a source jig, spacing bars, a shutter, a control unit and a beta dose meter calibration stand. For 740 MBq 147 Pm and 74 MBq 90 Sr + 90 Y beta reference radiations with compensation filters and 740 MBq 90 Sr + 90 Y beta reference radiation without compensation filter, at 20 cm, 30 cm and 30 cm distance separately; the residual energy of maximum is 0.14 MeV, 1.98 MeV and 2.18 MeV separately; the absorbed dose to tissue D (0.07) is 1.547 mGy/h (1996-05-20), 5.037 mGy/h (1996-05-10) and 93.57 mGy/h (1996-05-15) separately; the total uncertainty is 3.0%, 1.7% and 1.7% separately. For the first and the second beta reference radiation, the dose rate variability in the area of 18 cm diameter in the plane perpendicular to the beta-ray beam axis is within +-6% and +-3% separately. (3 refs., 2 tabs., 8 figs.)

  6. VBE reference framework

    NARCIS (Netherlands)

    Afsarmanesh, H.; Camarinha-Matos, L.M.; Ermilova, E.; Camarinha-Matos, L.M.; Afsarmanesh, H.; Ollus, M.

    2008-01-01

    Defining a comprehensive and generic "reference framework" for Virtual organizations Breeding Environments (VBEs), addressing all their features and characteristics, is challenging. While the definition and modeling of VBEs has become more formalized during the last five years, "reference models"

  7. CMS Statistics Reference Booklet

    Data.gov (United States)

    U.S. Department of Health & Human Services — The annual CMS Statistics reference booklet provides a quick reference for summary information about health expenditures and the Medicare and Medicaid health...

  8. Detection of signals in noise

    CERN Document Server

    Whalen, Anthony D; Declaris, Nicholas

    1971-01-01

    Detection of Signals in Noise serves as an introduction to the principles and applications of the statistical theory of signal detection. The book discusses probability and random processes; narrowband signals, their complex representation, and their properties described with the aid of the Hilbert transform; and Gaussian-derived processes. The text also describes the application of hypothesis testing for the detection of signals and the fundamentals required for statistical detection of signals in noise. Problem exercises, references, and a supplementary bibliography are included after each c

  9. Changing quantum reference frames

    OpenAIRE

    Palmer, Matthew C.; Girelli, Florian; Bartlett, Stephen D.

    2013-01-01

    We consider the process of changing reference frames in the case where the reference frames are quantum systems. We find that, as part of this process, decoherence is necessarily induced on any quantum system described relative to these frames. We explore this process with examples involving reference frames for phase and orientation. Quantifying the effect of changing quantum reference frames serves as a first step in developing a relativity principle for theories in which all objects includ...

  10. Preparation, characterization and use of a reference material to proficiency testing for determination of metals in fish tissue in natura; Preparo, caracterizacao e uso de um material de referencia para ensaios de proficiencia para determinacao de metais em tecido de peixe in natura

    Energy Technology Data Exchange (ETDEWEB)

    Santana, Luciana Vieira de

    2013-07-01

    The proficiency tests are widely used to evaluate the analytical capacity of laboratories and also as part of the accreditation process. For this reason, are important tools for the control of the quality of the analytical results obtained in the laboratories that work directly with seafood companies. In Brazil there are no providers of proficiency testing for metals potentially toxic in fish tissues. In this work will be described all steps used for the production of reference materials to be used in a proficiency testing pilot study for As, Cd, Pb and Hg in fish tissue following the recommendations of the ISO Guide 35. He preparation scheme consisted in selecting the individuals, cleaning, grinding, homogenization and fortification with As, Cd and Pb in two concentration levels. The preparation resulted in 164 sachets of 10 g each. In order to evaluate the effect of gamma irradiation in the samples conservation 52 sachets were irradiated with {sup 60}Co (10.00 {+-} 1.05 kGy) in a gamma cell. This material with others non irradiated 52 sachets were used for the homogeneity and stability studies. The remaining 60 were used for the proficiency testing. The results demonstrated that both materials were homogeneous and presented good stability (during a period of 45 days). However, the irradiated material present better integrity, concerning biological degradation, when stored in ambient temperature. For this reason they were used to the proficiency testing pilot program. Ten laboratories participated in the proficiency testing pilot study and the results were evaluated using the following tests: z-score, confidence ellipse and En numbers. This work demonstrates the capability of the laboratory to produce reference materials as well as to organize and conduct proficiency testing. (author)

  11. Vitamin E deficiency depressed fish growth, disease resistance, and the immunity and structural integrity of immune organs in grass carp (Ctenopharyngodon idella): Referring to NF-κB, TOR and Nrf2 signaling.

    Science.gov (United States)

    Pan, Jia-Hong; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang

    2017-01-01

    This study investigated the effects of dietary vitamin E on growth, disease resistance and the immunity and structural integrity of head kidney, spleen and skin in grass carp (Ctenopharyngodon idella). The fish were fed six diets containing graded levels of vitamin E (0, 45, 90, 135, 180 and 225 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila. The results showed that compared with optimal vitamin E supplementation, vitamin E deficiency caused depressed growth, poor survival rates and increased skin lesion morbidity in grass carp. Meanwhile, vitamin E deficiency decreased lysozyme and acid phosphatase activities, complement component 3 and complement component 4 contents in the head kidney, spleen and skin of grass carp (P vitamin E deficiency down-regulated antimicrobial peptides (Hepcidin, liver-expressed antimicrobial peptide-2A, -2B, β-defensin), IL-10, TGFβ1, IκBα, TOR and S6K1 mRNA levels (P vitamin E deficiency caused oxidative damage, decreased superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione reductase (GR) activities, and down-regulated the mRNA levels of antioxidant enzymes and signaling molecules Nrf2 (P Vitamin E deficiency also induced apoptosis by up-regulating capase-2, -3, -7, and -8 mRNA levels in the head kidney, spleen and skin of grass carp. In conclusion, this study indicated that dietary vitamin E deficiency depressed fish growth, impaired the immune function and disturbed the structural integrity of the head kidney, spleen and skin in grass carp, but optimal vitamin E supplementation can reverse those negative effects in fish. The optimal vitamin E requirements for young grass carp (266.39-1026.63 g) to achieve optimal growth performance and disease resistance based on the percent weight gain (PWG) and skin lesion morbidity were estimated to be 116.2 and 130.9 mg/kg diet, respectively. Meanwhile, based on immune indicator (LA activity

  12. Revisiting the Logan plot to account for non-negligible blood volume in brain tissue.

    Science.gov (United States)

    Schain, Martin; Fazio, Patrik; Mrzljak, Ladislav; Amini, Nahid; Al-Tawil, Nabil; Fitzer-Attas, Cheryl; Bronzova, Juliana; Landwehrmeyer, Bernhard; Sampaio, Christina; Halldin, Christer; Varrone, Andrea

    2017-08-18

    Reference tissue-based quantification of brain PET data does not typically include correction for signal originating from blood vessels, which is known to result in biased outcome measures. The bias extent depends on the amount of radioactivity in the blood vessels. In this study, we seek to revisit the well-established Logan plot and derive alternative formulations that provide estimation of distribution volume ratios (DVRs) that are corrected for the signal originating from the vasculature. New expressions for the Logan plot based on arterial input function and reference tissue were derived, which included explicit terms for whole blood radioactivity. The new methods were evaluated using PET data acquired using [ 11 C]raclopride and [ 18 F]MNI-659. The two-tissue compartment model (2TCM), with which signal originating from blood can be explicitly modeled, was used as a gold standard. DVR values obtained for [ 11 C]raclopride using the either blood-based or reference tissue-based Logan plot were systematically underestimated compared to 2TCM, and for [ 18 F]MNI-659, a proportionality bias was observed, i.e., the bias varied across regions. The biases disappeared when optimal blood-signal correction was used for respective tracer, although for the case of [ 18 F]MNI-659 a small but systematic overestimation of DVR was still observed. The new method appears to remove the bias introduced due to absence of correction for blood volume in regular graphical analysis and can be considered in clinical studies. Further studies are however required to derive a generic mapping between plasma and whole-blood radioactivity levels.

  13. IAEA biological reference materials

    International Nuclear Information System (INIS)

    Parr, R.M.; Schelenz, R.; Ballestra, S.

    1988-01-01

    The Analytical Quality Control Services programme of the IAEA encompasses a wide variety of intercomparisons and reference materials. This paper reviews only those aspects of the subject having to do with biological reference materials. The 1988 programme foresees 13 new intercomparison exercises, one for major, minor and trace elements, five for radionuclides, and seven for stable isotopes. Twenty-two natural matrix biological reference materials are available: twelve for major, minor and trace elements, six for radionuclides, and four for chlorinated hydrocarbons. Seven new intercomparisons and reference materials are in preparation or under active consideration. Guidelines on the correct use of reference materials are being prepared for publication in 1989 in consultation with other major international producers and users of biological reference materials. The IAEA database on available reference materials is being updated and expanded in scope, and a new publication is planned for 1989. (orig.)

  14. Reference genes for normalization: A study of rat brain tissue

    DEFF Research Database (Denmark)

    Bonefeld, Birgit; Elfving, Betina; Wegener, Gregers

    2008-01-01

    are warranted. With the overall aim to inspect the gene expression of three target genes, NMDAR1, SORT, and CREB, in rat hippocampus, we tested a panel of eight HKGs, 18s rRNA, ActB, CycA, Gapd, Hmbs, Hprt1, Rpl13A, and Ywhaz in order to select the most stably expressed gene, using the NormFinder and ge...

  15. Electronic signal conditioning

    CERN Document Server

    NEWBY, BRUCE

    1994-01-01

    At technician level, brief references to signal conditioning crop up in a fragmented way in various textbooks, but there has been no single textbook, until now!More advanced texts do exist but they are more mathematical and presuppose a higher level of understanding of electronics and statistics. Electronic Signal Conditioning is designed for HNC/D students and City & Guilds Electronics Servicing 2240 Parts 2 & 3. It will also be useful for BTEC National, Advanced GNVQ, A-level electronics and introductory courses at degree level.

  16. Force transmission in epithelial tissues.

    Science.gov (United States)

    Vasquez, Claudia G; Martin, Adam C

    2016-03-01

    In epithelial tissues, cells constantly generate and transmit forces between each other. Forces generated by the actomyosin cytoskeleton regulate tissue shape and structure and also provide signals that influence cells' decisions to divide, die, or differentiate. Forces are transmitted across epithelia because cells are mechanically linked through junctional complexes, and forces can propagate through the cell cytoplasm. Here, we review some of the molecular mechanisms responsible for force generation, with a specific focus on the actomyosin cortex and adherens junctions. We then discuss evidence for how these mechanisms promote cell shape changes and force transmission in tissues. © 2016 Wiley Periodicals, Inc.

  17. Signaling aggression.

    Science.gov (United States)

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Genetics Home Reference: osteoarthritis

    Science.gov (United States)

    ... damage is caused as the body attempts to repair and rebuild these tissues. The immune system, which plays a role in ... the result of the body's failed attempts to repair this damage. In healthy ... of the tissue. This balance is lost in osteoarthritis , leading to ...

  19. Indoor air: Reference bibliography

    International Nuclear Information System (INIS)

    Campbell, D.; Staves, D.; McDonald, S.

    1989-07-01

    The U. S. Environmental Protection Agency initially established the indoor air Reference Bibliography in 1987 as an appendix to the Indoor Air Quality Implementation Plan. The document was submitted to Congress as required under Title IV--Radon Gas and Indoor Air Quality Research of the Superfund Amendments and Reauthorization Act of 1986. The Reference Bibliography is an extensive bibliography of reference materials on indoor air pollution. The Bibliography contains over 4500 citations and continues to increase as new articles appear

  20. Android quick APIs reference

    CERN Document Server

    Cinar, Onur

    2015-01-01

    The Android Quick APIs Reference is a condensed code and APIs reference for the new Google Android 5.0 SDK. It presents the essential Android APIs in a well-organized format that can be used as a handy reference. You won't find any technical jargon, bloated samples, drawn out history lessons, or witty stories in this book. What you will find is a software development kit and APIs reference that is concise, to the point and highly accessible. The book is packed with useful information and is a must-have for any mobile or Android app developer or programmer. In the Android Quick APIs Refe

  1. Signal detection

    International Nuclear Information System (INIS)

    Tholomier, M.

    1985-01-01

    In a scanning electron microscope, whatever is the measured signal, the same set is found: incident beam, sample, signal detection, signal amplification. The resulting signal is used to control the spot luminosity with the observer cathodoscope. This is synchronized with the beam scanning on the sample; on the cathodoscope, the image in secondary electrons, backscattered electrons,... of the sample surface is reconstituted. The best compromise must be found between a register time low enough to remove eventual variations (under the incident beam) of the nature of the observed phenomenon, and a good spatial resolution of the image and a signal-to-noise ratio high enough. The noise is one of the basic limitations of the scanning electron microscope performance. The whose measurement line must be optimized to reduce it [fr

  2. Marketing Reference Services.

    Science.gov (United States)

    Norman, O. Gene

    1995-01-01

    Relates the marketing concept to library reference services. Highlights include a review of the literature and an overview of marketing, including research, the marketing mix, strategic plan, marketing plan, and marketing audit. Marketing principles are applied to reference services through the marketing mix elements of product, price, place, and…

  3. Reference class forecasting

    DEFF Research Database (Denmark)

    Flyvbjerg, Bent

    optimisme og misinformation. RCF bygger på teorier, som vandt Daniel Kahneman Nobelprisen i økonomi i 2002. RCF estimerer budgettet for et givet projekt på grundlag af de faktiske udfald for budgetterne i en reference-klasse af projekter. RCF udføres i tre trin: 1. Identifikation af en relevant reference...

  4. Piezoelectric smart biomaterials for bone and cartilage tissue engineering.

    Science.gov (United States)

    Jacob, Jaicy; More, Namdev; Kalia, Kiran; Kapusetti, Govinda

    2018-01-01

    Tissues like bone and cartilage are remodeled dynamically for their functional requirements by signaling pathways. The signals are controlled by the cells and extracellular matrix and transmitted through an electrical and chemical synapse. Scaffold-based tissue engineering therapies largely disturb the natural signaling pathways, due to their rigidity towards signal conduction, despite their therapeutic advantages. Thus, there is a high need of smart biomaterials, which can conveniently generate and transfer the bioelectric signals analogous to native tissues for appropriate physiological functions. Piezoelectric materials can generate electrical signals in response to the applied stress. Furthermore, they can stimulate the signaling pathways and thereby enhance the tissue regeneration at the impaired site. The piezoelectric scaffolds can act as sensitive mechanoelectrical transduction systems. Hence, it is applicable to the regions, where mechanical loads are predominant. The present review is mainly concentrated on the mechanism related to the electrical stimulation in a biological system and the different piezoelectric materials suitable for bone and cartilage tissue engineering.

  5. Noise cancellation in magnetoencephalography and electroencephalography with isolated reference sensors

    Science.gov (United States)

    Kraus, Jr., Robert H.; Espy, Michelle A.; Matlachov, Andrei; Volegov, Petr

    2010-06-01

    An apparatus measures electromagnetic signals from a weak signal source. A plurality of primary sensors is placed in functional proximity to the weak signal source with an electromagnetic field isolation surface arranged adjacent the primary sensors and between the weak signal source and sources of ambient noise. A plurality of reference sensors is placed adjacent the electromagnetic field isolation surface and arranged between the electromagnetic isolation surface and sources of ambient noise.

  6. Activation of natural killer T cells promotes M2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via the IL-4/STAT6 signaling axis in obesity

    NARCIS (Netherlands)

    Ji, Yewei; Sun, Shengyi; Xu, Aimin; Yang, Liu; Bhargava, Prerna; Lam, Karen S.; Gao, Bin; Lee, Chih-Hao; Kersten, Sander; Qi, Ling

    2012-01-01

    Natural killer T (NKT) cells are important therapeutic targets in various disease models and under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type-1

  7. Activation of natural killer T Cells promotes M2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signalling axis in obesity

    NARCIS (Netherlands)

    Ji, Y.; Sun, S.; Xu, Aimin; Bhargava, P.; Yang, Liu; Lam, K.S.L.; Gao, Bin; Lee, Chih-Hao; Kersten, A.H.; Qi, L.

    2012-01-01

    Natural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type

  8. Genetics Home Reference: hypochondrogenesis

    Science.gov (United States)

    ... Achondrogenesis Health Topic: Connective Tissue Disorders Health Topic: Dwarfism Additional NIH Resources (1 link) National Institute of ... T, Nishimura G, Watanabe H, Arisaka O. Prenatal diagnosis of hypochondrogenesis using fetal MRI: a case report. ...

  9. The CEBAF fiber optic phase reference system

    International Nuclear Information System (INIS)

    Crawford, K.; Simrock, S.; Hovater, C.; Krycuk, A.

    1995-01-01

    The specified phase stability of the CEBAF RF distribution system is 2.9 degree rms per linac. Stability is achieved through the use of a temperature and pressure regulated coaxial drive line. Purpose of the fiber optic phase reference system is to monitor the relative phase at the beginning and ending of this drive line, between linacs, injector and separator to determine drift due to ambient temperature fluctuations. The system utilizes an Ortel 1310 nm single mode laser driving Sumitumo optical fiber to distribute a reference signal at 1497 MHz. Phase of this reference signal is compared to the 1427 MHz (LO) and the 70 MHz (IF) via a 360 degree phase detector. The detected information is then routed to the CEBAF control system for display with a specified resolution of ±0.2 degree over a 20 degree phase delta

  10. Uranium reference materials

    International Nuclear Information System (INIS)

    Donivan, S.; Chessmore, R.

    1987-07-01

    The Technical Measurements Center has prepared uranium mill tailings reference materials for use by remedial action contractors and cognizant federal and state agencies. Four materials were prepared with varying concentrations of radionuclides, using three tailings materials and a river-bottom soil diluent. All materials were ground, dried, and blended thoroughly to ensure homogeneity. The analyses on which the recommended values for nuclides in the reference materials are based were performed, using independent methods, by the UNC Geotech (UNC) Chemistry Laboratory, Grand Junction, Colorado, and by C.W. Sill (Sill), Idaho National Engineering Laboratory, Idaho Falls, Idaho. Several statistical tests were performed on the analytical data to characterize the reference materials. Results of these tests reveal that the four reference materials are homogeneous and that no large systematic bias exists between the analytical methods used by Sill and those used by TMC. The average values for radionuclides of the two data sets, representing an unbiased estimate, were used as the recommended values for concentrations of nuclides in the reference materials. The recommended concentrations of radionuclides in the four reference materials are provided. Use of these reference materials will aid in providing uniform standardization among measurements made by remedial action contractors. 11 refs., 9 tabs

  11. Deep soft tissue leiomyoma of the thigh

    International Nuclear Information System (INIS)

    Watson, G.M.T.; Saifuddin, A.; Sandison, A.

    1999-01-01

    A case of ossified leiomyoma of the deep soft tissues of the left thigh is presented. The radiographic appearance suggested a low-grade chondrosarcoma. MRI of the lesion showed signal characteristics similar to muscle on both T1- and T2-weighted spin echo sequences with linear areas of high signal intensity on T1-weighted images consistent with medullary fat in metaplastic bone. Histopathological examination of the resected specimen revealed a benign ossified soft tissue leiomyoma. (orig.)

  12. STL pocket reference

    CERN Document Server

    Lischner, Ray

    2003-01-01

    The STL Pocket Reference describes the functions, classes, and templates in that part of the C++ standard library often referred to as the Standard Template Library (STL). The STL encompasses containers, iterators, algorithms, and function objects, which collectively represent one of the most important and widely used subsets of standard library functionality. The C++ standard library, even the subset known as the STL, is vast. It's next to impossible to work with the STL without some sort of reference at your side to remind you of template parameters, function invocations, return types--ind

  13. Handbook of reference electrodes

    CERN Document Server

    Inzelt, György; Scholz, Fritz

    2013-01-01

    Reference Electrodes are a crucial part of any electrochemical system, yet an up-to-date and comprehensive handbook is long overdue. Here, an experienced team of electrochemists provides an in-depth source of information and data for the proper choice and construction of reference electrodes. This includes all kinds of applications such as aqueous and non-aqueous solutions, ionic liquids, glass melts, solid electrolyte systems, and membrane electrodes. Advanced technologies such as miniaturized, conducting-polymer-based, screen-printed or disposable reference electrodes are also covered. Essen

  14. Regular Expression Pocket Reference

    CERN Document Server

    Stubblebine, Tony

    2007-01-01

    This handy little book offers programmers a complete overview of the syntax and semantics of regular expressions that are at the heart of every text-processing application. Ideal as a quick reference, Regular Expression Pocket Reference covers the regular expression APIs for Perl 5.8, Ruby (including some upcoming 1.9 features), Java, PHP, .NET and C#, Python, vi, JavaScript, and the PCRE regular expression libraries. This concise and easy-to-use reference puts a very powerful tool for manipulating text and data right at your fingertips. Composed of a mixture of symbols and text, regular exp

  15. Neptunium: a bibliographic reference

    International Nuclear Information System (INIS)

    Mosley, R.E.

    1979-06-01

    A comprehensive bibliograhy of the literature on the element neptunium published prior to January 1976 is presented. A short abstract is given for each listed reference, with a few exceptions. The references are divided into sections categorized as General, Man-Made Sources (Reactors), Man-Made Sources (Fuel Reprocessing), Chemistry (Solubility), Chemistry (Compounds), Chemistry (Isotopes), Analyses (Instrumental), Analyses (Chemical), Chemical (Animal), Biological (Effects), Biological (Animal-Metabolism-Retention), Biological (Air Movement), Biological (Human Inhalation), Measurement, and Dosimetry. The bibliography contains author and keyword indexes and was compiled to serve as a quick reference source for neptunium-related work. 184 citations

  16. CSS Pocket Reference

    CERN Document Server

    Meyer, Eric

    2011-01-01

    When you're working with CSS and need a quick answer, CSS Pocket Reference delivers. This handy, concise book provides all of the essential information you need to implement CSS on the fly. Ideal for intermediate to advanced web designers and developers, the 4th edition is revised and updated for CSS3, the latest version of the Cascading Style Sheet specification. Along with a complete alphabetical reference to CSS3 selectors and properties, you'll also find a short introduction to the key concepts of CSS. Based on Cascading Style Sheets: The Definitive Guide, this reference is an easy-to-us

  17. LINQ Pocket Reference

    CERN Document Server

    Albahari, Joseph

    2008-01-01

    Ready to take advantage of LINQ with C# 3.0? This guide has the detail you need to grasp Microsoft's new querying technology, and concise explanations to help you learn it quickly. And once you begin to apply LINQ, the book serves as an on-the-job reference when you need immediate reminders. All the examples in the LINQ Pocket Reference are preloaded into LINQPad, the highly praised utility that lets you work with LINQ interactively. Created by the authors and free to download, LINQPad will not only help you learn LINQ, it will have you thinking in LINQ. This reference explains: LINQ's ke

  18. R quick syntax reference

    CERN Document Server

    Tollefson, Margot

    2014-01-01

    The R Quick Syntax Reference is a handy reference book detailing the intricacies of the R language. Not only is R a free, open-source tool, R is powerful, flexible, and has state of the art statistical techniques available. With the many details which must be correct when using any language, however, the R Quick Syntax Reference makes using R easier.Starting with the basic structure of R, the book takes you on a journey through the terminology used in R and the syntax required to make R work. You will find looking up the correct form for an expression quick and easy. With a copy of the R Quick

  19. Genetics Home Reference: limb-girdle muscular dystrophy

    Science.gov (United States)

    ... These complexes maintain the physical integrity of muscle tissue and allow the muscles to contract. Other proteins participate in cell signaling, cell membrane repair, or the removal of potentially toxic wastes from ...

  20. Optical Characterization of Tissue Phantoms Using a Silicon Integrated fdNIRS System on Chip.

    Science.gov (United States)

    Sthalekar, Chirag C; Miao, Yun; Koomson, Valencia Joyner

    2017-04-01

    An interface circuit with signal processing and digitizing circuits for a high frequency, large area avalanche photodiode (APD) has been integrated in a 130 nm BiCMOS chip. The system enables the absolute oximetry of tissue using frequency domain Near Infrared Spectroscopy (fdNIRS). The system measures the light absorbed and scattered by the tissue by measuring the reduction in the amplitude of signal and phase shift introduced between the light source and detector which are placed a finite distance away from each other. The received 80 MHz RF signal is downconverted to a low frequency and amplified using a heterodyning scheme. The front-end transimpedance amplifier has a 3-level programmable gain that increases the dynamic range to 60 dB. The phase difference between an identical reference channel and the optical channel is measured with a 0.5° accuracy. The detectable current range is [Formula: see text] and with a 40 A/W reponsivity using the APD, power levels as low as 500 pW can be detected. Measurements of the absorption and reduced scattering coefficients of solid tissue phantoms using this system are compared with those using a commercial instrument with differences within 30%. Measurement of a milk based liquid tissue phantom show an increase in absorption coefficient with addition of black ink. The miniaturized circuit serves as an efficiently scalable system for multi-site detection for applications in neonatal cerebral oximetry and optical mammography.

  1. Tissue irradiator

    International Nuclear Information System (INIS)

    Hungate, F.P.; Riemath, W.F.; Bunnell, L.R.

    1975-01-01

    A tissue irradiator is provided for the in-vivo irradiation of body tissue. The irradiator comprises a radiation source material contained and completely encapsulated within vitreous carbon. An embodiment for use as an in-vivo blood irradiator comprises a cylindrical body having an axial bore therethrough. A radioisotope is contained within a first portion of vitreous carbon cylindrically surrounding the axial bore, and a containment portion of vitreous carbon surrounds the radioisotope containing portion, the two portions of vitreous carbon being integrally formed as a single unit. Connecting means are provided at each end of the cylindrical body to permit connections to blood-carrying vessels and to provide for passage of blood through the bore. In a preferred embodiment, the radioisotope is thulium-170 which is present in the irradiator in the form of thulium oxide. A method of producing the preferred blood irradiator is also provided, whereby nonradioactive thulium-169 is dispersed within a polyfurfuryl alcohol resin which is carbonized and fired to form the integral vitreous carbon body and the device is activated by neutron bombardment of the thulium-169 to produce the beta-emitting thulium-170

  2. Transforming growth factor beta 1 increases collagen content, and stimulates procollagen I and tissue inhibitor of metalloproteinase-1 production of dental pulp cells: Role of MEK/ERK and activin receptor-like kinase-5/Smad signaling

    Directory of Open Access Journals (Sweden)

    Po-Shuen Lin

    2017-05-01

    Conclusion: These results indicate that TGF-β1 may be involved in the healing/regeneration processes of dental pulp in response to injury by stimulation of collagen and TIMP-1 production. These events are associated with activin receptor-like kinase-5/Smad2/3 and MEK/ERK signaling.

  3. Optimal primitive reference frames

    International Nuclear Information System (INIS)

    Jennings, David

    2011-01-01

    We consider the smallest possible directional reference frames allowed and determine the best one can ever do in preserving quantum information in various scenarios. We find that for the preservation of a single spin state, two orthogonal spins are optimal primitive reference frames; and in a product state, they do approximately 22% as well as an infinite-sized classical frame. By adding a small amount of entanglement to the reference frame, this can be raised to 2(2/3) 5 =26%. Under the different criterion of entanglement preservation, a very similar optimal reference frame is found; however, this time it is for spins aligned at an optimal angle of 87 deg. In this case 24% of the negativity is preserved. The classical limit is considered numerically, and indicates under the criterion of entanglement preservation, that 90 deg. is selected out nonmonotonically, with a peak optimal angle of 96.5 deg. for L=3 spins.

  4. Reference Climatological Stations

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Reference Climatological Stations (RCS) network represents the first effort by NOAA to create and maintain a nationwide network of stations located only in areas...

  5. Toxicity Reference Database

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxicity Reference Database (ToxRefDB) contains approximately 30 years and $2 billion worth of animal studies. ToxRefDB allows scientists and the interested...

  6. Python essential reference

    CERN Document Server

    Beazley, David M

    2009-01-01

    Python Essential Reference is the definitive reference guide to the Python programming language — the one authoritative handbook that reliably untangles and explains both the core Python language and the most essential parts of the Python library. Designed for the professional programmer, the book is concise, to the point, and highly accessible. It also includes detailed information on the Python library and many advanced subjects that is not available in either the official Python documentation or any other single reference source. Thoroughly updated to reflect the significant new programming language features and library modules that have been introduced in Python 2.6 and Python 3, the fourth edition of Python Essential Reference is the definitive guide for programmers who need to modernize existing Python code or who are planning an eventual migration to Python 3. Programmers starting a new Python project will find detailed coverage of contemporary Python programming idioms.

  7. Collaborative networks: Reference modeling

    NARCIS (Netherlands)

    Camarinha-Matos, L.M.; Afsarmanesh, H.

    2008-01-01

    Collaborative Networks: Reference Modeling works to establish a theoretical foundation for Collaborative Networks. Particular emphasis is put on modeling multiple facets of collaborative networks and establishing a comprehensive modeling framework that captures and structures diverse perspectives of

  8. Ozone Standard Reference Photometer

    Data.gov (United States)

    Federal Laboratory Consortium — The Standard Reference Photometer (SRP) Program began in the early 1980s as collaboration between NIST and the U.S. Environmental Protection Agency (EPA) to design,...

  9. Enterprise Reference Library

    Science.gov (United States)

    Bickham, Grandin; Saile, Lynn; Havelka, Jacque; Fitts, Mary

    2011-01-01

    Introduction: Johnson Space Center (JSC) offers two extensive libraries that contain journals, research literature and electronic resources. Searching capabilities are available to those individuals residing onsite or through a librarian s search. Many individuals have rich collections of references, but no mechanisms to share reference libraries across researchers, projects, or directorates exist. Likewise, information regarding which references are provided to which individuals is not available, resulting in duplicate requests, redundant labor costs and associated copying fees. In addition, this tends to limit collaboration between colleagues and promotes the establishment of individual, unshared silos of information The Integrated Medical Model (IMM) team has utilized a centralized reference management tool during the development, test, and operational phases of this project. The Enterprise Reference Library project expands the capabilities developed for IMM to address the above issues and enhance collaboration across JSC. Method: After significant market analysis for a multi-user reference management tool, no available commercial tool was found to meet this need, so a software program was built around a commercial tool, Reference Manager 12 by The Thomson Corporation. A use case approach guided the requirements development phase. The premise of the design is that individuals use their own reference management software and export to SharePoint when their library is incorporated into the Enterprise Reference Library. This results in a searchable user-specific library application. An accompanying share folder will warehouse the electronic full-text articles, which allows the global user community to access full -text articles. Discussion: An enterprise reference library solution can provide a multidisciplinary collection of full text articles. This approach improves efficiency in obtaining and storing reference material while greatly reducing labor, purchasing and

  10. Comparability of reference values

    International Nuclear Information System (INIS)

    Rossbach, M.; Stoeppler, M.

    1993-01-01

    Harmonization of certified values in Reference Materials (RMs) can be carried out by applying nuclear analytical techniques to RMs of various matrix types and concentration levels. Although RMs generally should not be used as primary standards the cross evaluation of concentrations in RMs leads to better compatibility of reference values and thus to a greater agreement between analytical results from different laboratories using these RMs for instrument calibration and quality assurance. (orig.)

  11. Electronics engineer's reference book

    CERN Document Server

    Turner, L W

    1976-01-01

    Electronics Engineer's Reference Book, 4th Edition is a reference book for electronic engineers that reviews the knowledge and techniques in electronics engineering and covers topics ranging from basics to materials and components, devices, circuits, measurements, and applications. This edition is comprised of 27 chapters; the first of which presents general information on electronics engineering, including terminology, mathematical equations, mathematical signs and symbols, and Greek alphabet and symbols. Attention then turns to the history of electronics; electromagnetic and nuclear radiatio

  12. 2002 reference document

    International Nuclear Information System (INIS)

    2002-01-01

    This 2002 reference document of the group Areva, provides information on the society. Organized in seven chapters, it presents the persons responsible for the reference document and for auditing the financial statements, information pertaining to the transaction, general information on the company and share capital, information on company operation, changes and future prospects, assets, financial position, financial performance, information on company management and executive board and supervisory board, recent developments and future prospects. (A.L.B.)

  13. NBS activities in biological reference materials

    Energy Technology Data Exchange (ETDEWEB)

    Rasberry, S.D.

    1988-12-01

    NBS activities in biological reference materials during 1986-1988 are described with a preview of plans for future certifications of reference materials. During the period, work has been completed or partially completed on about 40 reference materials of importance to health, nutrition, and environmental quality. Some of the reference materials that have been completed during the period and are described include: creatinine (SRM 914a), bovine serum albumin (SRM 927a), cholesterol in human serum (SRM's 1951-1952), aspartate aminotransferase (RM 8430), cholesterol and fat-soluble vitamins in coconut oil (SRM 1563), wheat flour (SRM 1567a), rice flour (SRM 1568a), mixed diet (RM 8431a), dinitropyrene isomers and 1-nitropyrene (SRM 1596), and complex PAH's from coal tar (SRM 1597). Oyster tissue (SRM 1566a) is being analyzed and should be available in 1988.

  14. Practical obstacles and their mitigation strategies in compressional optical coherence elastography of biological tissues

    Directory of Open Access Journals (Sweden)

    Vladimir Y. Zaitsev

    2017-11-01

    Full Text Available In this paper, we point out some practical obstacles arising in realization of compressional optical coherence elastography (OCE that have not attracted sufficient attention previously. Specifically, we discuss (i complications in quantification of the Young modulus of tissues related to partial adhesion between the OCE probe and soft intervening reference layer sensor, (ii distorting influence of tissue surface curvature/corrugation on the subsurface strain distribution mapping, (iii ways of signal-to-noise ratio (SNR enhancement in OCE strain mapping when periodic averaging is not realized, and (iv potentially significant influence of tissue elastic nonlinearity on quantification of its stiffness. Potential practical approaches to mitigate the effects of these complications are also described.

  15. Electromagnetic pulse distortion in living tissue

    NARCIS (Netherlands)

    Lepelaars, E.S.A.M.

    1996-01-01

    Insight into the distortion of electromagnetic (EM) signals in living tissue is important for optimising medical applications. To obtain this insight, field calculations have been carried out for a plane-stratified configuration of air, skin, fat, muscle and bone tissue. In this configuration, an EM

  16. Molecular, cellular, and tissue engineering

    CERN Document Server

    Bronzino, Joseph D

    2015-01-01

    Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering. Molecular, Cellular, and Tissue Engineering, the fourth volume of the handbook, presents material from respected scientists with diverse backgrounds in molecular biology, transport phenomena, physiological modeling, tissue engineering, stem cells, drug delivery systems, artificial organs, and personalized medicine. More than three dozen specific topics are examined, including DNA vaccines, biomimetic systems, cardiovascular dynamics, biomaterial scaffolds, cell mechanobiology, synthetic biomaterials, pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, nanobiomaterials for tissue engineering, biomedical imaging of engineered tissues, gene therapy, noninvasive targeted protein and peptide drug deliver...

  17. With Reference to Reference Genes: A Systematic Review of Endogenous Controls in Gene Expression Studies.

    Science.gov (United States)

    Chapman, Joanne R; Waldenström, Jonas

    2015-01-01

    The choice of reference genes that are stably expressed amongst treatment groups is a crucial step in real-time quantitative PCR gene expression studies. Recent guidelines have specified that a minimum of two validated reference genes should be used for normalisation. However, a quantitative review of the literature showed that the average number of reference genes used across all studies was 1.2. Thus, the vast majority of studies continue to use a single gene, with β-actin (ACTB) and/or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) being commonly selected in studies of vertebrate gene expression. Few studies (15%) tested a panel of potential reference genes for stability of expression before using them to normalise data. Amongst studies specifically testing reference gene stability, few found ACTB or GAPDH to be optimal, whereby these genes were significantly less likely to be chosen when larger panels of potential reference genes were screened. Fewer reference genes were tested for stability in non-model organisms, presumably owing to a dearth of available primers in less well characterised species. Furthermore, the experimental conditions under which real-time quantitative PCR analyses were conducted had a large influence on the choice of reference genes, whereby different studies of rat brain tissue showed different reference genes to be the most stable. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies.

  18. Reference Device-Assisted Adaptive Location Fingerprinting

    Directory of Open Access Journals (Sweden)

    Dongjin Wu

    2016-06-01

    Full Text Available Location fingerprinting suffers in dynamic environments and needs recalibration from time to time to maintain system performance. This paper proposes an adaptive approach for location fingerprinting. Based on real-time received signal strength indicator (RSSI samples measured by a group of reference devices, the approach applies a modified Universal Kriging (UK interpolant to estimate adaptive temporal and environmental radio maps. The modified UK can take the spatial distribution characteristics of RSSI into account. In addition, the issue of device heterogeneity caused by multiple reference devices is further addressed. To compensate the measuring differences of heterogeneous reference devices, differential RSSI metric is employed. Extensive experiments were conducted in an indoor field and the results demonstrate that the proposed approach not only adapts to dynamic environments and the situation of changing APs’ positions, but it is also robust toward measuring differences of heterogeneous reference devices.

  19. Esophageal tissue engineering: a new approach for esophageal replacement.

    Science.gov (United States)

    Totonelli, Giorgia; Maghsoudlou, Panagiotis; Fishman, Jonathan M; Orlando, Giuseppe; Ansari, Tahera; Sibbons, Paul; Birchall, Martin A; Pierro, Agostino; Eaton, Simon; De Coppi, Paolo

    2012-12-21

    A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds

  20. Reference costs of electricity

    International Nuclear Information System (INIS)

    Terraz, N.

    1997-01-01

    The calculation of electric power production reference costs is used in France, even in the present case of over-capacity, for comparing the relative interest of the various means of power generation (nuclear plants, coal plants, hydroelectricity, gas combined cycles, etc.) and as an aid for future investment decisions. Reference costs show a sharp decrease between 1993 and 1997 due to advancements in nuclear plant operating ability and fossil fuel price decrease. Actuarial rates, plant service life, fuel costs and exchange rates are important parameters. The various costs from the research stage to the waste processing stages are discussed and the reference costs of the various power generation systems are presented and compared together with their competitiveness; the future of wind energy and cogeneration and the prospective of the renewal of nuclear plants at the 2010 horizon are also addressed

  1. Setting reference targets

    International Nuclear Information System (INIS)

    Ruland, R.E.

    1997-04-01

    Reference Targets are used to represent virtual quantities like the magnetic axis of a magnet or the definition of a coordinate system. To explain the function of reference targets in the sequence of the alignment process, this paper will first briefly discuss the geometry of the trajectory design space and of the surveying space, then continue with an overview of a typical alignment process. This is followed by a discussion on magnet fiducialization. While the magnetic measurement methods to determine the magnetic centerline are only listed (they will be discussed in detail in a subsequent talk), emphasis is given to the optical/mechanical methods and to the task of transferring the centerline position to reference targets

  2. Genetics Home Reference: pilomatricoma

    Science.gov (United States)

    ... before birth, as well as the maintenance and repair of adult tissues. Among its many activities, beta-catenin appears to be necessary for the normal function of hair follicles . This protein is active in cells that make up a part of the hair ...

  3. Electrical engineer's reference book

    CERN Document Server

    Jones, G R

    2013-01-01

    A long established reference book: radical revision for the fifteenth edition includes complete rearrangement to take in chapters on new topics and regroup the subjects covered for easy access to information.The Electrical Engineer's Reference Book, first published in 1945, maintains its original aims: to reflect the state of the art in electrical science and technology and cater for the needs of practising engineers. Most chapters have been revised and many augmented so as to deal properly with both fundamental developments and new technology and applications that have come to the fore since

  4. Python pocket reference

    CERN Document Server

    Lutz, Mark

    2010-01-01

    This is the book to reach for when you're coding on the fly and need an answer now. It's an easy-to-use reference to the core language, with descriptions of commonly used modules and toolkits, and a guide to recent changes, new features, and upgraded built-ins -- all updated to cover Python 3.X as well as version 2.6. You'll also quickly find exactly what you need with the handy index. Written by Mark Lutz -- widely recognized as the world's leading Python trainer -- Python Pocket Reference, Fourth Edition, is the perfect companion to O'Reilly's classic Python tutorials, also written by Mark

  5. The Reference Return Ratio

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Faber Frandsen, Tove

    2008-01-01

    The paper introduces a new journal impact measure called The Reference Return Ratio (3R). Unlike the traditional Journal Impact Factor (JIF), which is based on calculations of publications and citations, the new measure is based on calculations of bibliographic investments (references) and returns...... (citations). A comparative study of the two measures shows a strong relationship between the 3R and the JIF. Yet, the 3R appears to correct for citation habits, citation dynamics, and composition of document types - problems that typically are raised against the JIF. In addition, contrary to traditional...

  6. Perl Pocket Reference

    CERN Document Server

    Vromans, Johan

    2011-01-01

    If you have a Perl programming question, you'll find the answer quickly in this handy, easy-to-use quick reference. The Perl Pocket Reference condenses and organizes stacks of documentation down to the most essential facts, so you can find what you need in a heartbeat. Updated for Perl 5.14, the 5th edition provides a summary of Perl syntax rules and a complete list of operators, built-in functions, and other features. It's the perfect companion to O'Reilly's authoritative and in-depth Perl programming books, including Learning Perl, Programming Perl, and the Perl Cookbook..

  7. HTML & XHTML Pocket Reference

    CERN Document Server

    Robbins, Jennifer

    2010-01-01

    After years of using spacer GIFs, layers of nested tables, and other improvised solutions for building your web sites, getting used to the more stringent standards-compliant design can be intimidating. HTML and XHTML Pocket Reference is the perfect little book when you need answers immediately. Jennifer Niederst-Robbins, author Web Design in a Nutshell, has revised and updated the fourth edition of this pocket guide by taking the top 20% of vital reference information from her Nutshell book, augmenting it judiciously, cross-referencing everything, and organizing it according to the most com

  8. CSS Pocket Reference

    CERN Document Server

    Meyer, Eric A

    2007-01-01

    They say that good things come in small packages, and it's certainly true for this edition of CSS Pocket Reference. Completely revised and updated to reflect the latest Cascading Style Sheet specifications in CSS 2.1, this indispensable little book covers the most essential information that web designers and developers need to implement CSS effectively across all browsers. Inside, you'll find: A short introduction to the key concepts of CSS A complete alphabetical reference to all CSS 2.1 selectors and properties A chart displaying detailed information about CSS support for every style ele

  9. JDBC Pocket Reference

    CERN Document Server

    Bales, Donald

    2003-01-01

    JDBC--the Java Database Connectivity specification--is a complex set of application programming interfaces (APIs) that developers need to understand if they want their Java applications to work with databases. JDBC is so complex that even the most experienced developers need to refresh their memories from time to time on specific methods and details. But, practically speaking, who wants to stop and thumb through a weighty tutorial volume each time a question arises? The answer is the JDBC Pocket Reference, a data-packed quick reference that is both a time-saver and a lifesaver. The JDBC P

  10. Reference values for electrooculography

    International Nuclear Information System (INIS)

    Barrientos Castanno, Alberto; Herrera Mora, Maritza; Garcia Baez, Obel

    2012-01-01

    Obtain electrooculographic reference values based on the patterns set by the Standardization Committee of the International Society for Clinical Electrophysiology of Vision (ISCEV). the lowest amplitude values of the potential ranged between 388 and 882 μv in the dark phase. The light peak was obtained between 9 and 10 minutes, and during this phase the potential reached an amplitude ranging between 808 and 1 963 μv. This amplitude variability may be related to the fact that the test was conducted without pupillary mydriasis. The reference value obtained for Arden index was 1,55 to 2,87

  11. NASCAP programmer's reference manual

    Science.gov (United States)

    Mandell, M. J.; Stannard, P. R.; Katz, I.

    1993-05-01

    The NASA Charging Analyzer Program (NASCAP) is a computer program designed to model the electrostatic charging of complicated three-dimensional objects, both in a test tank and at geosynchronous altitudes. This document is a programmer's reference manual and user's guide. It is designed as a reference to experienced users of the code, as well as an introduction to its use for beginners. All of the many capabilities of NASCAP are covered in detail, together with examples of their use. These include the definition of objects, plasma environments, potential calculations, particle emission and detection simulations, and charging analysis.

  12. Reference: 753 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available otypes, XLG3 and AGB1 each positively regulate root waving and root skewing. Since these responses are regul...s of root-waving and root-skewing responses in plants and possibly interact in a tissue-specific or signal-s...pecific manner. Because plants harboring knockout mutations in the Galpha subunit gene, GPA1, exhibit wild-type root waving and skewi...ng, our results may indicate that the AGB1 subunit funct

  13. Signal Processing

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Signal processing techniques, extensively used nowadays to maximize the performance of audio and video equipment, have been a key part in the design of hardware and software for high energy physics detectors since pioneering applications in the UA1 experiment at CERN in 1979

  14. Electrothermal frequency reference

    NARCIS (Netherlands)

    Makinwa, K.A.A.; Kashmiri, S.M.

    2011-01-01

    An electrothermal frequency-locked loop (EFLL) circuit is described. This EFLL circuit includes an oscillator in a feedback loop. A drive circuit in the EFLL circuit generates a first signal having a fundamental frequency, and an electrothermal filter (ETF) in the EFLL circuit provides a second

  15. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

    Energy Technology Data Exchange (ETDEWEB)

    Lunsing, Roelineke J.; Strating, Kim [University Medical Centre Groningen, University of Groningen, Department of Child Neurology, Groningen (Netherlands); Koning, Tom J. de [University Medical Centre Groningen, University of Groningen, Department of Pediatric Metabolic Diseases, Groningen (Netherlands); Sijens, Paul E. [University Medical Centre Groningen, University of Groningen, Department of Radiology, Groningen (Netherlands)

    2017-03-15

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  16. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

    International Nuclear Information System (INIS)

    Lunsing, Roelineke J.; Strating, Kim; Koning, Tom J. de; Sijens, Paul E.

    2017-01-01

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  17. Book Catalogs; Selected References.

    Science.gov (United States)

    Brandhorst, Wesley T.

    The 116 citations on book catalogs are divided into the following two main sections: (1) Selected References, in alphabetic sequence by personal or institutional author and (2) Anonymous Entries, in alphabetic sequence by title. One hundred and seven of the citations cover the years 1960 through March 1969. There are five scattered citations in…

  18. ROOT Reference Documentation

    CERN Document Server

    Fuakye, Eric Gyabeng

    2017-01-01

    A ROOT Reference Documentation has been implemented to generate all the lists of libraries needed for each ROOT class. Doxygen has no option to generate or add the lists of libraries for each ROOT class. Therefore shell scripting and a basic C++ program was employed to import the lists of libraries needed by each ROOT class.

  19. Hospitality Services Reference Book.

    Science.gov (United States)

    Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

    This reference book provides information needed by employees in hospitality services occupations. It includes 29 chapters that cover the following topics: the hospitality services industry; professional ethics; organization and management structures; safety practices and emergency procedures; technology; property maintenance and repair; purchasing…

  20. Quantum frames of reference

    International Nuclear Information System (INIS)

    Kaufherr, T.

    1981-01-01

    The idea that only relative variables have physical meaning came to be known as Mach's principle. Carrying over this idea to quantum theory, has led to the consideration of finite mass, macroscopic reference frames, relative to which all physical quantities are measured. During the process of measurement, a finite mass observer receives a kickback, and this reaction of the measuring device is not negligible in quantum theory because of the quantization of the action. Hence, the observer himself has to be included in the system that is being considered. Using this as the starting point, a number of thought experiments involving finite mass observers is discussed which have quantum uncertainties in their time or in their position. These thought experiments serve to elucidate in a qualitative way some of the difficulties involved, as well as pointing out a direction to take in seeking solutions to them. When the discussion is extended to include more than one observer, the question of the covariance of the theory immediately arises. Because none of the frames of reference should be preferred, the theory should be covariant. This demand expresses an equivalence principle which here is extended to include reference frames which are in quantum uncertainties relative to each other. Formulating the problem in terms of canonical variables, the ensueing free Hamiltonian contains vector and scalar potentials which represent the kick that the reference frame receives during measurement. These are essentially gravitational type potentials, resulting, as it were, from the extension of the equivalence principle into the quantum domain

  1. Pollen reference collection digitization

    NARCIS (Netherlands)

    Ercan, F.E.Z.; Donders, T.H.; Bijl, P.K.; Wagner, F.

    2016-01-01

    The extensive Utrecht University pollen reference collection holds thousands of pollen samples of many species and genera from all over the world and has been a basis for the widely-used North West European Pollen Flora. These samples are fixed on glass slides for microscopy use, but the aging

  2. Virtual Reference Services.

    Science.gov (United States)

    Brewer, Sally

    2003-01-01

    As the need to access information increases, school librarians must create virtual libraries. Linked to reliable reference resources, the virtual library extends the physical collection and library hours and lets students learn to use Web-based resources in a protected learning environment. The growing number of virtual schools increases the need…

  3. Reference-Dependent Sympathy

    Science.gov (United States)

    Small, Deborah A.

    2010-01-01

    Natural disasters and other traumatic events often draw a greater charitable response than do ongoing misfortunes, even those that may cause even more widespread misery, such as famine or malaria. Why is the response disproportionate to need? The notion of reference dependence critical to Prospect Theory (Kahneman & Tversky, 1979) maintains that…

  4. Genetics Home Reference

    Science.gov (United States)

    ... Page Search Home Health Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email Facebook Twitter Genetics Home Reference provides consumer-friendly information about the effects of genetic variation on human health. Health Conditions More than 1,200 health ...

  5. Python library reference

    NARCIS (Netherlands)

    G. van Rossum (Guido)

    1995-01-01

    textabstractPython is an extensible, interpreted, object-oriented programming language. It supports a wide range of applications, from simple text processing scripts to interactive WWW browsers. While the Python Reference Manual describes the exact syntax and semantics of the language, it does not

  6. Signal processing for radiation detectors

    CERN Document Server

    Nakhostin, Mohammad

    2018-01-01

    This book provides a clear understanding of the principles of signal processing of radiation detectors. It puts great emphasis on the characteristics of pulses from various types of detectors and offers a full overview on the basic concepts required to understand detector signal processing systems and pulse processing techniques. Signal Processing for Radiation Detectors covers all of the important aspects of signal processing, including energy spectroscopy, timing measurements, position-sensing, pulse-shape discrimination, and radiation intensity measurement. The book encompasses a wide range of applications so that readers from different disciplines can benefit from all of the information. In addition, this resource: * Describes both analog and digital techniques of signal processing * Presents a complete compilation of digital pulse processing algorithms * Extrapolates content from more than 700 references covering classic papers as well as those of today * Demonstrates concepts with more than 340 origin...

  7. Phonocardiography Signal Processing

    CERN Document Server

    Abbas, Abbas K

    2009-01-01

    The auscultation method is an important diagnostic indicator for hemodynamic anomalies. Heart sound classification and analysis play an important role in the auscultative diagnosis. The term phonocardiography refers to the tracing technique of heart sounds and the recording of cardiac acoustics vibration by means of a microphone-transducer. Therefore, understanding the nature and source of this signal is important to give us a tendency for developing a competent tool for further analysis and processing, in order to enhance and optimize cardiac clinical diagnostic approach. This book gives the

  8. Acute swelling of the limbs: magnetic resonance pictorial review of fascial and muscle signal changes

    Energy Technology Data Exchange (ETDEWEB)

    Revelon, Geraldine [Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Rahmouni, Alain [Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Jazaerli, Nedal [Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Godeau, Bertrand [Department of Internal Medicine, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Chosidow, Olivier [Department of Dermatology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Authier, Jerome [Department of Pathology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Mathieu, Didier [Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Roujeau, Jean-Claude [Department of Dermatology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Vasile, Norbert [Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France)

    1999-04-01

    Objective: This pictorial review analyzes the magnetic resonance (MR) fascial/muscular changes in 69 patients referred as emergencies with acute swelling of the limbs (ASL) from various causes. Methods and material: A prospective MR imaging (MRI) study of 69 patients referred as emergencies for ASL was performed. Our population consisted of 45 patients with skin and soft-tissue infections (cellulitis and necrotizing fasciitis, and pyomyositis), six patients with soft-tissue inflammatory diseases (dermatomyositis, graft-versus-host disease), 11 patients with acute deep venous thrombosis, three patients with rhabdomyolysis, one patient with acute denervation and three other patients with rare diseases. Hematomas, tumorous or infectious bone involvement and soft-tissue tumors were excluded. All studies included spin echo T1-weighted images and spin echo T2-weighted images. Gadolinium-enhanced spin echo T1-weighted images were obtained when an abscess was suspected on T2-weighted images. Selective fat-saturated T1- and T2-weighted sequences were also used. MRI analysis was performed to obtain a compartmentalized anatomical approach according to the location of signal abnormalities in subcutaneous fat, superficial and deep fascia and muscle. Results: In all patients with ASL, MRI demonstrated soft-tissue abnormalities involving subcutaneous fat, superficial fascia, deep fascia, or muscle. Although MR findings were non-specific, MRI appears sensitive for detecting subtle fascial and muscle signal changes. Conclusions: In skin and soft-tissue infections, MRI can be helpful for therapeutic management by determining the depth of soft-tissue involvement, particularly within fasciae and muscles, which is partly related to the severity of cellulitis with severe systemic manifestations. MRI can also aid the surgeon in diagnosing abscesses. In inflammatory diseases, MRI can determine the best site for biopsy and also monitor therapeutic response.

  9. Tissue engineered tumor models.

    Science.gov (United States)

    Ingram, M; Techy, G B; Ward, B R; Imam, S A; Atkinson, R; Ho, H; Taylor, C R

    2010-08-01

    Many research programs use well-characterized tumor cell lines as tumor models for in vitro studies. Because tumor cells grown as three-dimensional (3-D) structures have been shown to behave more like tumors in vivo than do cells growing in monolayer culture, a growing number of investigators now use tumor cell spheroids as models. Single cell type spheroids, however, do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. We describe here a method for generating, reproducibly, more realistic 3-D tumor models that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. Because they are so tissue-like we refer to them as tumor histoids. They can be generated reproducibly in substantial quantities. The bioreactor developed to generate histoid constructs is described and illustrated. It accommodates disposable culture chambers that have filled volumes of either 10 or 64 ml, each culture yielding on the order of 100 or 600 histoid particles, respectively. Each particle is a few tenths of a millimeter in diameter. Examples of histological sections of tumor histoids representing cancers of breast, prostate, colon, pancreas and urinary bladder are presented. Potential applications of tumor histoids include, but are not limited to, use as surrogate tumors for pre-screening anti-solid tumor pharmaceutical agents, as reference specimens for immunostaining in the surgical pathology laboratory and use in studies of invasive properties of cells or other aspects of tumor development and progression. Histoids containing nonmalignant cells also may have potential as "seeds" in tissue engineering. For drug testing, histoids probably will have to meet certain criteria of size and tumor cell content. Using a COPAS Plus flow cytometer, histoids containing fluorescent tumor cells were analyzed successfully and sorted using such criteria.

  10. Evidence of non-canonical NOTCH signaling

    DEFF Research Database (Denmark)

    Traustadóttir, Gunnhildur Ásta; Jensen, Charlotte H; Thomassen, Mads

    2016-01-01

    Dlk1(+/+) and Dlk1(-/-) mouse tissues at E16.5, we demonstrated that several NOTCH signaling pathways indeed are affected by DLK1 during tissue development, and this was supported by a lower activation of NOTCH1 protein in Dlk1(+/+) embryos. Likewise, but using a distinct Dlk1-manipulated (si...

  11. Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces

    Science.gov (United States)

    Boys, Alexander J.; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J.; Estroff, Lara A.

    2017-01-01

    Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors. PMID:29333332

  12. ``Frames of Reference'' revisited

    Science.gov (United States)

    Steyn-Ross, Alistair; Ivey, Donald G.

    1992-12-01

    The PSSC teaching film, ``Frames of Reference,'' was made in 1960, and was one of the first audio-visual attempts at showing how your physical ``point of view,'' or frame of reference, necessarily alters both your perceptions and your observations of motion. The gentle humor and original demonstrations made a lasting impact on many audiences, and with its recent re-release as part of the AAPT Cinema Classics videodisc it is timely that we should review both the message and the methods of the film. An annotated script and photographs from the film are presented, followed by extension material on rotating frames which teachers may find appropriate for use in their classrooms: constructions, demonstrations, an example, and theory.

  13. Program reference schedule baseline

    International Nuclear Information System (INIS)

    1986-07-01

    This Program Reference Schedule Baseline (PRSB) provides the baseline Program-level milestones and associated schedules for the Civilian Radioactive Waste Management Program. It integrates all Program-level schedule-related activities. This schedule baseline will be used by the Director, Office of Civilian Radioactive Waste Management (OCRWM), and his staff to monitor compliance with Program objectives. Chapter 1 includes brief discussions concerning the relationship of the PRSB to the Program Reference Cost Baseline (PRCB), the Mission Plan, the Project Decision Schedule, the Total System Life Cycle Cost report, the Program Management Information System report, the Program Milestone Review, annual budget preparation, and system element plans. Chapter 2 includes the identification of all Level 0, or Program-level, milestones, while Chapter 3 presents and discusses the critical path schedules that correspond to those Level 0 milestones

  14. OSH technical reference manual

    Energy Technology Data Exchange (ETDEWEB)

    1993-11-01

    In an evaluation of the Department of Energy (DOE) Occupational Safety and Health programs for government-owned contractor-operated (GOCO) activities, the Department of Labor`s Occupational Safety and Health Administration (OSHA) recommended a technical information exchange program. The intent was to share written safety and health programs, plans, training manuals, and materials within the entire DOE community. The OSH Technical Reference (OTR) helps support the secretary`s response to the OSHA finding by providing a one-stop resource and referral for technical information that relates to safe operations and practice. It also serves as a technical information exchange tool to reference DOE-wide materials pertinent to specific safety topics and, with some modification, as a training aid. The OTR bridges the gap between general safety documents and very specific requirements documents. It is tailored to the DOE community and incorporates DOE field experience.

  15. Electrical engineer's reference book

    CERN Document Server

    Laughton, M A

    1985-01-01

    Electrical Engineer's Reference Book, Fourteenth Edition focuses on electrical engineering. The book first discusses units, mathematics, and physical quantities, including the international unit system, physical properties, and electricity. The text also looks at network and control systems analysis. The book examines materials used in electrical engineering. Topics include conducting materials, superconductors, silicon, insulating materials, electrical steels, and soft irons and relay steels. The text underscores electrical metrology and instrumentation, steam-generating plants, turbines

  16. Reference Sources in Chemistry

    OpenAIRE

    Sthapit, Dilip Man

    1995-01-01

    Information plays an important role in the development of every field. Therefore a brief knowledge regarding information sources is necessary to function in any field. There are many information sources about scientific and technical subjects. In this context there are many reference sources in Chemistry too. Chemistry is one important part of the science which deals with the study of the composition of substances and the chemical changes that they undergo. The purpose of this report is...

  17. Radioactive certified reference materials

    International Nuclear Information System (INIS)

    Watanabe, Kazuo

    2010-01-01

    Outline of radioactive certified reference materials (CRM) for the analysis of nuclear materials and radioactive nuclides were described. The nuclear fuel CRMs are supplied by the three institutes: NBL in the US, CETAMA in France and IRMM in Belgium. For the RI CRMs, the Japan Radioisotope Association is engaged in activities concerning supply. The natural-matrix CRMs for the analysis of trace levels of radio-nuclides are prepared and supplied by NIST in the US and the IAEA. (author)

  18. Reference Japanese man

    International Nuclear Information System (INIS)

    Tanaka, G.-I.; Kawamura, H.; Nakahara, Y.

    1979-01-01

    The weight of organs from autopsy cases of normal Japanese adults, children, and infants is presented for the purpose of approaching a Reference Japanese Man. The skeletal content and the daily intake of alkaline earth elements are given. A lower rate of transfer (K 2 ) to the thyroid gland of ingested radioiodine, as well as a remarkably shorter biological half-life than the data adopted by ICRP, is also proved as a result of this study. (author)

  19. Reference handbook: Level detectors

    International Nuclear Information System (INIS)

    1990-01-01

    The purpose of this handbook is to provide Rocky Flats personnel with the information necessary to understand level measurement and detection. Upon completion of this handbook you should be able to do the following: List three reasons for measuring level. Describe the basic operating principles of the sight glass. Demonstrate proper techniques for reading a sight glass. Describe the basic operating principles of a float level detector. Describe the basic operating principles of a bubbler level indicating system. Explain the differences between a wet and dry reference leg indicating system, and describe how each functions. This handbook is designed for use by experienced Rocky Flats operators to reinforce and improve their current knowledge level, and by entry-level operators to ensure that they possess a minimum level of fundamental knowledge. Level Detectors is applicable to many job classifications and can be used as a reference for classroom work or for self-study. Although this reference handbook is by no means all-encompassing, you will gain enough information about this subject area to assist you in contributing to the safe operation of Rocky Flats Plant

  20. Electroacoustical reference data

    CERN Document Server

    Eargle, John M

    2002-01-01

    The need for a general collection of electroacoustical reference and design data in graphical form has been felt by acousticians and engineers for some time. This type of data can otherwise only be found in a collection of handbooks. Therefore, it is the author's intention that this book serve as a single source for many electroacoustical reference and system design requirements. In form, the volume closely resembles Frank Massa's Acoustic Design Charts, a handy book dating from 1942 that has long been out of print. The basic format of Massa's book has been followed here: For each entry, graphical data are presented on the right page, while text, examples, and refer­ ences appear on the left page. In this manner, the user can solve a given problem without thumbing from one page to the next. All graphs and charts have been scaled for ease in data entry and reading. The book is divided into the following sections: A. General Acoustical Relationships. This section covers the behavior of sound transmis­ sion in...

  1. Crosslinkable Hydrogels Derived from Cartilage, Meniscus, and Tendon Tissue

    NARCIS (Netherlands)

    Visser, Jetze; Levett, Peter A.; te Moller, Nikae C. R.; Besems, Jeremy; Boere, Kristel W. M.; van Rijen, Mattie H. P.; de Grauw, Janny C.; Dhert, Wouter J. A.; van Weeren, P. Rene; Malda, J

    2015-01-01

    Decellularized tissues have proven to be versatile matrices for the engineering of tissues and organs. These matrices usually consist of collagens, matrix-specific proteins, and a set of largely undefined growth factors and signaling molecules. Although several decellularized tissues have found

  2. Integrin Signalling

    OpenAIRE

    Schelfaut, Roselien

    2005-01-01

    Integrins are receptors presented on most cells. By binding ligand they can generate signalling pathways inside the cell. Those pathways are a linkage to proteins in the cytosol. It is known that tumor cells can survive and proliferate in the absence of a solid support while normal cells need to be bound to ligand. To understand why tumour cells act that way, we first have to know how ligand-binding to integrins affect the cell. This research field includes studies on activation of proteins b...

  3. Reference-shaping adaptive control by using gradient descent optimizers.

    Directory of Open Access Journals (Sweden)

    Baris Baykant Alagoz

    Full Text Available This study presents a model reference adaptive control scheme based on reference-shaping approach. The proposed adaptive control structure includes two optimizer processes that perform gradient descent optimization. The first process is the control optimizer that generates appropriate control signal for tracking of the controlled system output to a reference model output. The second process is the adaptation optimizer that performs for estimation of a time-varying adaptation gain, and it contributes to improvement of control signal generation. Numerical update equations derived for adaptation gain and control signal perform gradient descent optimization in order to decrease the model mismatch errors. To reduce noise sensitivity of the system, a dead zone rule is applied to the adaptation process. Simulation examples show the performance of the proposed Reference-Shaping Adaptive Control (RSAC method for several test scenarios. An experimental study demonstrates application of method for rotor control.

  4. Perceptions about tissue donation for medical research among ...

    African Journals Online (AJOL)

    Background: Tissue banking refers to a structured and organized resource collection of tissue. Recent advances in research technology and knowledge in the fields of human genetics/ genomics highlights the need to maintain a steady supply of tissue for researchers. Objective: To assess the perception and willingness of ...

  5. Instrumentation reference book

    CERN Document Server

    Boyes, Walt

    2002-01-01

    Instrumentation is not a clearly defined subject, having a 'fuzzy' boundary with a number of other disciplines. Often categorized as either 'techniques' or 'applications' this book addresses the various applications that may be needed with reference to the practical techniques that are available for the instrumentation or measurement of a specific physical quantity or quality. This makes it of direct interest to anyone working in the process, control and instrumentation fields where these measurements are essential.* Comprehensive and authoritative collection of technical information* Writte

  6. XSLT 10 Pocket Reference

    CERN Document Server

    Lenz, Evan

    2008-01-01

    XSLT is an essential tool for converting XML into other kinds of documents: HTML, PDF file, and many others. It's a critical technology for XML-based platforms such as Microsoft .NET, Sun Microsystems' Sun One, as well as for most web browsers and authoring tools. As useful as XSLT is, however, most people have a difficult time getting used to its peculiar characteristics. The ability to use advanced techniques depends on a clear and exact understanding of how XSLT templates work and interact. The XSLT 1.0 Pocket Reference from O'Reilly wants to make sure you achieve that level of understan

  7. Electronics engineer's reference book

    CERN Document Server

    Mazda, F F

    1989-01-01

    Electronics Engineer's Reference Book, Sixth Edition is a five-part book that begins with a synopsis of mathematical and electrical techniques used in the analysis of electronic systems. Part II covers physical phenomena, such as electricity, light, and radiation, often met with in electronic systems. Part III contains chapters on basic electronic components and materials, the building blocks of any electronic design. Part IV highlights electronic circuit design and instrumentation. The last part shows the application areas of electronics such as radar and computers.

  8. International Geomagnetic Reference Field

    DEFF Research Database (Denmark)

    Finlay, Chris; Maus, S.; Beggan, C. D.

    2010-01-01

    The eleventh generation of the International Geomagnetic Reference Field (IGRF) was adopted in December 2009 by the International Association of Geomagnetism and Aeronomy Working Group V‐MOD. It updates the previous IGRF generation with a definitive main field model for epoch 2005.0, a main field...... model for epoch 2010.0, and a linear predictive secular variation model for 2010.0–2015.0. In this note the equations defining the IGRF model are provided along with the spherical harmonic coefficients for the eleventh generation. Maps of the magnetic declination, inclination and total intensity...

  9. Mechanical engineer's reference book

    CERN Document Server

    Parrish, A

    1973-01-01

    Mechanical Engineer's Reference Book: 11th Edition presents a comprehensive examination of the use of Systéme International d' Unités (SI) metrication. It discusses the effectiveness of such a system when used in the field of engineering. It addresses the basic concepts involved in thermodynamics and heat transfer. Some of the topics covered in the book are the metallurgy of iron and steel; screw threads and fasteners; hole basis and shaft basis fits; an introduction to geometrical tolerancing; mechanical working of steel; high strength alloy steels; advantages of making components as castings

  10. VBScript pocket reference

    CERN Document Server

    Lomax, Paul; Petrusha, Ron

    2008-01-01

    Microsoft's Visual Basic Scripting Edition (VBScript), a subset of Visual Basic for Applications, is a powerful language for Internet application development, where it can serve as a scripting language for server-side, client-side, and system scripting. Whether you're developing code for Active Server Pages, client-side scripts for Internet Explorer, code for Outlook forms, or scripts for Windows Script Host, VBScript Pocket Reference will be your constant companion. Don't let the pocket-friendly format fool you. Based on the bestsellingVBScript in a Nutshell, this small book details every V

  11. Xcode 5 developer reference

    CERN Document Server

    Wentk, Richard

    2014-01-01

    Design, code, and build amazing apps with Xcode 5 Thanks to Apple's awesome Xcode development environment, you can create the next big app for Macs, iPhones, iPads, or iPod touches. Xcode 5 contains gigabytes of great stuff to help you develop for both OS X and iOS devices - things like sample code, utilities, companion applications, documentation, and more. And with Xcode 5 Developer Reference, you now have the ultimate step-by-step guide to it all. Immerse yourself in the heady and lucrative world of Apple app development, see how to tame the latest features and functions, and find loads of

  12. NUnit Pocket Reference

    CERN Document Server

    Hamilton, Bill

    2009-01-01

    The open source NUnit framework is an excellent way to test .NET code as it is written, saving hundreds of QA hours and headaches. Unfortunately, some of those hours saved can be wasted trying to master this popular but under-documented framework. Proof that good things come in small packages, the NUnit Pocket Reference is everything you need to get NUnit up and working for you. It's the only book you'll need on this popular and practical new open source framework.

  13. Coal Data: A reference

    International Nuclear Information System (INIS)

    1991-01-01

    The purpose of Coal Data: A Reference is to provide basic information on the mining and use of coal, an important source of energy in the United States. The report is written for a general audience. The goal is to cover basic material and strike a reasonable compromise between overly generalized statements and detailed analyses. The section ''Coal Terminology and Related Information'' provides additional information about terms mentioned in the text and introduces new terms. Topics covered are US coal deposits, resources and reserves, mining, production, employment and productivity, health and safety, preparation, transportation, supply and stocks, use, coal, the environment, and more. (VC)

  14. Quorum Quenching Revisited—From Signal Decays to Signalling Confusion

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2012-04-01

    Full Text Available In a polymicrobial community, while some bacteria are communicating with neighboring cells (quorum sensing, others are interrupting the communication (quorum quenching, thus creating a constant arms race between intercellular communication. In the past decade, numerous quorum quenching enzymes have been found and initially thought to inactivate the signalling molecules. Though this is widely accepted, the actual roles of these quorum quenching enzymes are now being uncovered. Recent evidence extends the role of quorum quenching to detoxification or metabolism of signalling molecules as food and energy source; this includes “signalling confusion”, a term coined in this paper to refer to the phenomenon of non-destructive modification of signalling molecules. While quorum quenching has been explored as a novel anti-infective therapy targeting, quorum sensing evidence begins to show the development of resistance against quorum quenching.

  15. Roaming Reference: Reinvigorating Reference through Point of Need Service

    Directory of Open Access Journals (Sweden)

    Kealin M. McCabe

    2011-11-01

    Full Text Available Roaming reference service was pursued as a way to address declining reference statistics. The service was staffed by librarians armed with iPads over a period of six months during the 2010-2011 academic year. Transactional statistics were collected in relation to query type (Research, Facilitative or Technology, location and approach (librarian to patron, patron to librarian or via chat widget. Overall, roaming reference resulted in an additional 228 reference questions, 67% (n=153 of which were research related. Two iterations of the service were implemented, roaming reference as a standalone service (Fall 2010 and roaming reference integrated with traditional reference desk duties (Winter 2011. The results demonstrate that although the Weller Library’s reference transactions are declining annually, they are not disappearing. For a roaming reference service to succeed, it must be a standalone service provided in addition to traditional reference services. The integration of the two reference models (roaming reference and reference desk resulted in a 56% decline in the total number of roaming reference questions from the previous term. The simple act of roaming has the potential to reinvigorate reference services as a whole, forcing librarians outside their comfort zones, allowing them to reach patrons at their point of need.

  16. AREVA - 2013 Reference document

    International Nuclear Information System (INIS)

    2014-01-01

    This Reference Document contains information on the AREVA group's objectives, prospects and development strategies, as well as estimates of the markets, market shares and competitive position of the AREVA group. Content: 1 - Person responsible for the Reference Document; 2 - Statutory auditors; 3 - Selected financial information; 4 - Description of major risks confronting the company; 5 - Information about the issuer; 6 - Business overview; 7 - Organizational structure; 8 - Property, plant and equipment; 9 - Situation and activities of the company and its subsidiaries; 10 - Capital resources; 11 - Research and development programs, patents and licenses; 12 - Trend information; 13 - Profit forecasts or estimates; 14 - Management and supervisory bodies; 15 - Compensation and benefits; 16 - Functioning of the management and supervisory bodies; 17 - Human resources information; 18 - Principal shareholders; 19 - Transactions with related parties; 20 - Financial information concerning assets, financial positions and financial performance; 21 - Additional information; 22 - Major contracts; 23 - Third party information, statements by experts and declarations of interest; 24 - Documents on display; 25 - Information on holdings; Appendix 1: report of the supervisory board chairman on the preparation and organization of the board's activities and internal control procedures; Appendix 2: statutory auditors' reports; Appendix 3: environmental report; Appendix 4: non-financial reporting methodology and independent third-party report on social, environmental and societal data; Appendix 5: ordinary and extraordinary general shareholders' meeting; Appendix 6: values charter; Appendix 7: table of concordance of the management report; glossaries

  17. Balinese Frame of Reference

    Directory of Open Access Journals (Sweden)

    I Nyoman Aryawibawa

    2016-04-01

    Full Text Available Abstract: Balinese Frame of Reference. Wassmann and Dasen (1998 did a study on the acquisition of Balinese frames of reference. They pointed out that, in addition to the dominant use of absolute system, the use of relative system was also observed. This article aims at verifying Wassmann and Dasen’ study. Employing monolingual Balinese speakers and using linguistic and non-linguistic tasks, Aryawibawa (2010, 2012, 2015 showed that Balinese subjects used an absolute system dominantly in responding the two tasks, e.g. The man is north/south/east/west of the car. Unlike Wassmann and Dasen’s results, no relative system was used by the subjects in solving the tasks. Instead of the relative system, an intrinsic system was also observed in this study, even though it was unfrequent. The article concludes that the absolute system was dominantly employed by Balinese speakers in describing spatial relations in Balinese. The use of the system seems to affect their cognitive functions.

  18. Antares Reference Telescope System

    International Nuclear Information System (INIS)

    Viswanathan, V.K.; Kaprelian, E.; Swann, T.; Parker, J.; Wolfe, P.; Woodfin, G.; Knight, D.

    1983-01-01

    Antares is a 24-beam, 40-TW carbon-dioxide laser-fusion system currently nearing completion at the Los Alamos National Laboratory. The 24 beams will be focused onto a tiny target (typically 300 to 1000 μm in diameter) located approximately at the center of a 7.3-m-diameter by 9.3-m-long vacuum (10 - 6 torr) chamber. The design goal is to position the targets to within 10 μm of a selected nominal position, which may be anywhere within a fixed spherical region 1 cm in diameter. The Antares Reference Telescope System is intended to help achieve this goal for alignment and viewing of the various targets used in the laser system. The Antares Reference Telescope System consists of two similar electro-optical systems positioned in a near orthogonal manner in the target chamber area of the laser. Each of these consists of four subsystems: (1) a fixed 9X optical imaging subsystem which produces an image of the target at the vidicon; (2) a reticle projection subsystem which superimposes an image of the reticle pattern at the vidicon; (3) an adjustable front-lighting subsystem which illuminates the target; and (4) an adjustable back-lighting subsystem which also can be used to illuminate the target. The various optical, mechanical, and vidicon design considerations and trade-offs are discussed. The final system chosen (which is being built) and its current status are described in detail

  19. CELLULAR CONTROL OF CONNECTIVE TISSUE MATRIX TENSION†

    Science.gov (United States)

    Langevin, Helene M.; Nedergaard, Maiken; Howe, Alan

    2013-01-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function and cancer. PMID:23444198

  20. Cellular control of connective tissue matrix tension.

    Science.gov (United States)

    Langevin, Helene M; Nedergaard, Maiken; Howe, Alan K

    2013-08-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function, and cancer. Copyright © 2013 Wiley Periodicals, Inc.

  1. Sensor employing internal reference electrode

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention concerns a novel internal reference electrode as well as a novel sensing electrode for an improved internal reference oxygen sensor and the sensor employing same.......The present invention concerns a novel internal reference electrode as well as a novel sensing electrode for an improved internal reference oxygen sensor and the sensor employing same....

  2. Endogenizing Prospect Theory's Reference Point

    OpenAIRE

    Ulrich Schmidt; Horst Zank

    2010-01-01

    In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This note provides a foundation of prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

  3. Reference ionization chamber

    International Nuclear Information System (INIS)

    Golnik, N.; Zielczynski, M.

    1999-01-01

    The paper presents the design of ionization chamber devoted for the determination of the absolute value of the absorbed dose in tissue-equivalent material. The special attention was paid to ensure that the volume of the active gas cavity was constant and well known. A specific property of the chamber design is that the voltage insulators are 'invisible' from any point of the active volume. Such configuration ensures a very good time stability of the electrical field and defines the active volume. The active volume of the chamber was determined with accuracy of 0.3%. This resulted in accuracy of 0.8% in determination of the absorbed dose in the layer of material adherent to the gas cavity. The chamber was applied for calibration purposes at radiotherapy facility in Joint Institute for Nuclear Research in Dubna (Russia) and in the calibration laboratory of the Institute of Atomic Energy in Swierk. (author)

  4. Mixed Connective Tissue Disease

    Science.gov (United States)

    Mixed connective tissue disease Overview Mixed connective tissue disease has signs and symptoms of a combination of disorders — primarily lupus, scleroderma and polymyositis. For this reason, mixed connective tissue disease ...

  5. Undifferentiated Connective Tissue Disease

    Science.gov (United States)

    ... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... by Barbara Goldstein, MD (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...

  6. Soft Tissue Sarcoma

    Science.gov (United States)

    ... muscles, tendons, fat, and blood vessels. Soft tissue sarcoma is a cancer of these soft tissues. There ... have certain genetic diseases. Doctors diagnose soft tissue sarcomas with a biopsy. Treatments include surgery to remove ...

  7. Signal transforms in dynamic measurements

    CERN Document Server

    Layer, Edward

    2015-01-01

    This book is devoted to the analysis of measurement signals which requires specific mathematical operations like Convolution, Deconvolution, Laplace, Fourier, Hilbert, Wavelet or Z transform which are all presented in the present book. The different problems refer to the modulation of signals, filtration of disturbance as well as to the orthogonal signals and their use in digital form for the measurement of current, voltage, power and frequency are also widely discussed. All the topics covered in this book are presented in detail and illustrated by means of examples in MathCad and LabVIEW. This book provides a useful source for researchers, scientists and engineers who in their daily work are required to deal with problems of measurement and signal processing and can also be helpful to undergraduate students of electrical engineering.    

  8. AREVA 2009 reference document

    International Nuclear Information System (INIS)

    2009-01-01

    This Reference Document contains information on the AREVA group's objectives, prospects and development strategies. It contains information on the markets, market shares and competitive position of the AREVA group. This information provides an adequate picture of the size of these markets and of the AREVA group's competitive position. Content: 1 - Person responsible for the Reference Document and Attestation by the person responsible for the Reference Document; 2 - Statutory and Deputy Auditors; 3 - Selected financial information; 4 - Risks: Risk management and coverage, Legal risk, Industrial and environmental risk, Operating risk, Risk related to major projects, Liquidity and market risk, Other risk; 5 - Information about the issuer: History and development, Investments; 6 - Business overview: Markets for nuclear power and renewable energies, AREVA customers and suppliers, Overview and strategy of the group, Business divisions, Discontinued operations: AREVA Transmission and Distribution; 7 - Organizational structure; 8 - Property, plant and equipment: Principal sites of the AREVA group, Environmental issues that may affect the issuer's; 9 - Analysis of and comments on the group's financial position and performance: Overview, Financial position, Cash flow, Statement of financial position, Events subsequent to year-end closing for 2009; 10 - Capital Resources; 11 - Research and development programs, patents and licenses; 12 -trend information: Current situation, Financial objectives; 13 - Profit forecasts or estimates; 14 - Administrative, management and supervisory bodies and senior management; 15 - Compensation and benefits; 16 - Functioning of corporate bodies; 17 - Employees; 18 - Principal shareholders; 19 - Transactions with related parties: French state, CEA, EDF group; 20 - Financial information concerning assets, financial positions and financial performance; 21 - Additional information: Share capital, Certificate of incorporation and by-laws; 22 - Major

  9. The Fog signaling pathway: Insights into signaling in morphogenesis

    Science.gov (United States)

    Manning, Alyssa J.; Rogers, Stephen L.

    2014-01-01

    Epithelia form the building blocks of many tissue and organ types. Epithelial cells often form a contiguous 2-dimensional sheet that is held together by strong adhesions. The mechanical properties conferred by these adhesions allow the cells to undergo dramatic three-dimensional morphogenetic movements while maintaining cell–cell contacts during embryogenesis and post-embryonic development. The Drosophila Folded gastrulation pathway triggers epithelial cell shape changes that drive gastrulation and tissue folding and is one of the most extensively studied examples of epithelial morphogenesis. This pathway has yielded key insights into the signaling mechanisms and cellular machinery involved in epithelial remodeling. In this review, we discuss principles of morphogenesis and signaling that have been discovered through genetic and cell biological examination of this pathway. We also consider various regulatory mechanisms and the system's relevance to mammalian development. We propose future directions that will continue to broaden our knowledge of morphogenesis across taxa. PMID:25127992

  10. Areva - 2016 Reference document

    International Nuclear Information System (INIS)

    2017-01-01

    Areva supplies high added-value products and services to support the operation of the global nuclear fleet. The company is present throughout the entire nuclear cycle, from uranium mining to used fuel recycling, including nuclear reactor design and operating services. Areva is recognized by utilities around the world for its expertise, its skills in cutting-edge technologies and its dedication to the highest level of safety. Areva's 36,000 employees are helping build tomorrow's energy model: supplying ever safer, cleaner and more economical energy to the greatest number of people. This Reference Document contains information on Areva's objectives, prospects and development strategies. It contains estimates of the markets, market shares and competitive position of Areva

  11. A reference tristimulus colorimeter

    Science.gov (United States)

    Eppeldauer, George P.

    2002-06-01

    A reference tristimulus colorimeter has been developed at NIST with a transmission-type silicon trap detector (1) and four temperature-controlled filter packages to realize the Commission Internationale de l'Eclairage (CIE) x(λ), y(λ) and z(λ) color matching functions (2). Instead of lamp standards, high accuracy detector standards are used for the colorimeter calibration. A detector-based calibration procedure is being suggested for tristimulus colorimeters wehre the absolute spectral responsivity of the tristimulus channels is determined. Then, color (spectral) correct and peak (amplitude) normalization are applied to minimize uncertainties caused by the imperfect realizations of the CIE functions. As a result of the corrections, the chromaticity coordinates of stable light sources with different spectral power distributions can be measured with uncertainties less than 0.0005 (k=1).

  12. Tank characterization reference guide

    International Nuclear Information System (INIS)

    De Lorenzo, D.S.; DiCenso, A.T.; Hiller, D.B.; Johnson, K.W.; Rutherford, J.H.; Smith, D.J.; Simpson, B.C.

    1994-09-01

    Characterization of the Hanford Site high-level waste storage tanks supports safety issue resolution; operations and maintenance requirements; and retrieval, pretreatment, vitrification, and disposal technology development. Technical, historical, and programmatic information about the waste tanks is often scattered among many sources, if it is documented at all. This Tank Characterization Reference Guide, therefore, serves as a common location for much of the generic tank information that is otherwise contained in many documents. The report is intended to be an introduction to the issues and history surrounding the generation, storage, and management of the liquid process wastes, and a presentation of the sampling, analysis, and modeling activities that support the current waste characterization. This report should provide a basis upon which those unfamiliar with the Hanford Site tank farms can start their research

  13. Areva, reference document 2006

    International Nuclear Information System (INIS)

    2006-01-01

    This reference document contains information on the AREVA group's objectives, prospects and development strategies, particularly in Chapters 4 and 7. It contains information on the markets, market shares and competitive position of the AREVA group. Content: - 1 Person responsible for the reference document and persons responsible for auditing the financial statements; - 2 Information pertaining to the transaction (Not applicable); - 3 General information on the company and its share capital: Information on AREVA, on share capital and voting rights, Investment certificate trading, Dividends, Organization chart of AREVA group companies, Equity interests, Shareholders' agreements; - 4 Information on company operations, new developments and future prospects: Overview and strategy of the AREVA group, The Nuclear Power and Transmission and Distribution markets, The energy businesses of the AREVA group, Front End division, Reactors and Services division, Back End division, Transmission and Distribution division, Major contracts, The principal sites of the AREVA group, AREVA's customers and suppliers, Sustainable Development and Continuous Improvement, Capital spending programs, Research and development programs, intellectual property and trademarks, Risk and insurance; - 5 Assets - Financial position - Financial performance: Analysis of and comments on the group's financial position and performance, 2006 Human Resources Report, Environmental Report, Consolidated financial statements, Notes to the consolidated financial statements, AREVA SA financial statements, Notes to the corporate financial statements; 6 - Corporate Governance: Composition and functioning of corporate bodies, Executive compensation, Profit-sharing plans, AREVA Values Charter, Annual Combined General Meeting of Shareholders of May 3, 2007; 7 - Recent developments and future prospects: Events subsequent to year-end closing for 2006, Outlook; 8 - Glossary; 9 - Table of concordance

  14. Areva reference document 2007

    International Nuclear Information System (INIS)

    2008-01-01

    This reference document contains information on the AREVA group's objectives, prospects and development strategies, particularly in Chapters 4 and 7. It contains also information on the markets, market shares and competitive position of the AREVA group. Content: 1 - Person responsible for the reference document and persons responsible for auditing the financial statements; 2 - Information pertaining to the transaction (not applicable); 3 - General information on the company and its share capital: Information on Areva, Information on share capital and voting rights, Investment certificate trading, Dividends, Organization chart of AREVA group companies, Equity interests, Shareholders' agreements; 4 - Information on company operations, new developments and future prospects: Overview and strategy of the AREVA group, The Nuclear Power and Transmission and Distribution markets, The energy businesses of the AREVA group, Front End division, Reactors and Services division, Back End division, Transmission and Distribution division, Major contracts 140 Principal sites of the AREVA group, AREVA's customers and suppliers, Sustainable Development and Continuous Improvement, Capital spending programs, Research and Development programs, Intellectual Property and Trademarks, Risk and insurance; 5 - Assets financial position financial performance: Analysis of and comments on the group's financial position and performance, Human Resources report, Environmental report, Consolidated financial statements 2007, Notes to the consolidated financial statements, Annual financial statements 2007, Notes to the corporate financial statements; 6 - Corporate governance: Composition and functioning of corporate bodies, Executive compensation, Profit-sharing plans, AREVA Values Charter, Annual Ordinary General Meeting of Shareholders of April 17, 2008; 7 - Recent developments and future prospects: Events subsequent to year-end closing for 2007, Outlook; Glossary; table of concordance

  15. Genetics Home Reference: psoriatic arthritis

    Science.gov (United States)

    ... disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body ordinarily stops the inflammatory response to prevent damage to its own cells and tissues. Mechanical stress on the joints, such as occurs ...

  16. Deep soft tissue leiomyoma of the thigh

    Energy Technology Data Exchange (ETDEWEB)

    Watson, G.M.T.; Saifuddin, A. [Department of Radiology, The Royal National Orthopaedic Hospital Trust, Brockley Hill (United Kingdom); Sandison, A. [Department of Pathology, The Royal National Orthopaedic Hospital Trust, Stanmore, Middlesex (United Kingdom)

    1999-07-01

    A case of ossified leiomyoma of the deep soft tissues of the left thigh is presented. The radiographic appearance suggested a low-grade chondrosarcoma. MRI of the lesion showed signal characteristics similar to muscle on both T1- and T2-weighted spin echo sequences with linear areas of high signal intensity on T1-weighted images consistent with medullary fat in metaplastic bone. Histopathological examination of the resected specimen revealed a benign ossified soft tissue leiomyoma. (orig.) With 3 figs., 13 refs.

  17. MRI findings of inflammatory myofibroblastic tumor of the soft tissue

    International Nuclear Information System (INIS)

    Deng Demao; Meng Quanfei; Chen Yinming; Zhou Chunxiang; Gao Zhenhua; Yang Zheng; Wang Liantang

    2008-01-01

    Objective: To describe MR findings in inflammatory myofibroblastic tumor (IMT) of the soft tissue. Methods: MR manifestations of 11 cases of IMT of the soft tissue were retrospectively analyzed, and the MR findings were correlated with surgical and histological results. Results: The pathological classification of the tumors was type I in 1 case, type II in 4 cases, mainly type II admixed with type I in 3 cases, and mainly type II admixed with type III in 3 eases. In 4 cases with primary tumor, the tumors were spheroid in shape, with well-defined margin and pseudocapsule. In 2 eases with primary axillary tumor and 5 cases with recurrent tumor, the tumors were irregular in shape, with ill-defined margin and invasion of adjacent structures. The tumors were mainly isointensive in T 1 -weighted images. Tumors of different pathological classifications had different signal intensities in T 2 -weighted images: 1 case of type I tumor was bright; 4 cases of type II tumor and 3 cases of type II tumor admixed with type I tumor were slightly bright; 3 cases of type II tumor admixed with type III were isointense or slightly hypointense in signal. All of the 11 cases in the study exhibited 'pitaya cross-section sign' in T 2 -weighted sequence, which referred to discrete punctuate foci of relatively hypointensity in the background of hyperintensity, slightly hypointensity or isointensity. All of the 11 cases exhibited inhomogeneously significant enhancement after gadolinium administration. In the follow-up of the 6 eases of primary tumor, 4 cases had recurrence, 1 case had no recurrence, and 1 case was lost in the follow-up process. In the follow-up of the 5 cases of recurrent tumor, 4 cases showed recurrence again, and 3 cases were lost in the follow-up process. Conclusions: The IMT of the soft tissue has characteristic MR features. The signal intensity of the tumor on T2-weighted sequence could reflect the pathological type of the tumor' to some extent. 'pitaya cross

  18. Simulation of ultrasound interaction with tissue

    International Nuclear Information System (INIS)

    Edee, M.K.A.; Ogulu, A.

    1995-08-01

    We model the effect of an ultrasound beam on a water phantom by considering water as an incompressible Newtonian viscous fluid. The two-dimensional flow velocities (u,v) induced in the water phantom, mimic displacement in living tissues for a phantom of unit width. The displacements depend on the ultrasound signal which is emitted and the model also predicts the nature of the signal received. 13 refs, 3 figs

  19. Corrected Four-Sphere Head Model for EEG Signals.

    Science.gov (United States)

    Næss, Solveig; Chintaluri, Chaitanya; Ness, Torbjørn V; Dale, Anders M; Einevoll, Gaute T; Wójcik, Daniel K

    2017-01-01

    The EEG signal is generated by electrical brain cell activity, often described in terms of current dipoles. By applying EEG forward models we can compute the contribution from such dipoles to the electrical potential recorded by EEG electrodes. Forward models are key both for generating understanding and intuition about the neural origin of EEG signals as well as inverse modeling, i.e., the estimation of the underlying dipole sources from recorded EEG signals. Different models of varying complexity and biological detail are used in the field. One such analytical model is the four-sphere model which assumes a four-layered spherical head where the layers represent brain tissue, cerebrospinal fluid (CSF), skull, and scalp, respectively. While conceptually clear, the mathematical expression for the electric potentials in the four-sphere model is cumbersome, and we observed that the formulas presented in the literature contain errors. Here, we derive and present the correct analytical formulas with a detailed derivation. A useful application of the analytical four-sphere model is that it can serve as ground truth to test the accuracy of numerical schemes such as the Finite Element Method (FEM). We performed FEM simulations of the four-sphere head model and showed that they were consistent with the corrected analytical formulas. For future reference we provide scripts for computing EEG potentials with the four-sphere model, both by means of the correct analytical formulas and numerical FEM simulations.

  20. Corrected Four-Sphere Head Model for EEG Signals

    Directory of Open Access Journals (Sweden)

    Solveig Næss

    2017-10-01

    Full Text Available The EEG signal is generated by electrical brain cell activity, often described in terms of current dipoles. By applying EEG forward models we can compute the contribution from such dipoles to the electrical potential recorded by EEG electrodes. Forward models are key both for generating understanding and intuition about the neural origin of EEG signals as well as inverse modeling, i.e., the estimation of the underlying dipole sources from recorded EEG signals. Different models of varying complexity and biological detail are used in the field. One such analytical model is the four-sphere model which assumes a four-layered spherical head where the layers represent brain tissue, cerebrospinal fluid (CSF, skull, and scalp, respectively. While conceptually clear, the mathematical expression for the electric potentials in the four-sphere model is cumbersome, and we observed that the formulas presented in the literature contain errors. Here, we derive and present the correct analytical formulas with a detailed derivation. A useful application of the analytical four-sphere model is that it can serve as ground truth to test the accuracy of numerical schemes such as the Finite Element Method (FEM. We performed FEM simulations of the four-sphere head model and showed that they were consistent with the corrected analytical formulas. For future reference we provide scripts for computing EEG potentials with the four-sphere model, both by means of the correct analytical formulas and numerical FEM simulations.

  1. Digital signal processing for NDT

    International Nuclear Information System (INIS)

    Georgel, B.

    1994-01-01

    NDT begins to adapt and use the most recent developments of digital signal and image processing. We briefly sum up the main characteristics of NDT situations (particularly noise and inverse problem formulation) and comment on techniques already used or just emerging (SAFT, split spectrum, adaptive learning network, noise reference filtering, stochastic models, neural networks). This survey is focused on ultrasonics, eddy currents and X-ray radiography. The final objective of end users (availability of automatic diagnosis systems) cannot be achieved only by signal processing algorithms. A close cooperation with other techniques such as artificial intelligence has therefore to be implemented. (author). 20 refs

  2. Signal processing for cognitive radios

    CERN Document Server

    Jayaweera, Sudharman K

    2014-01-01

    This book covers power electronics, in depth, by presenting the basic principles and application details, and it can be used both as a textbook and reference book.  Introduces the specific type of CR that has gained the most research attention in recent years: the CR for Dynamic Spectrum Access (DSA). Provides signal processing solutions to each task by relating the tasks to materials covered in Part II. Specialized chapters then discuss specific signal processing algorithms required for DSA and DSS cognitive radios  

  3. Canonical Wnt signaling in diabetic retinopathy.

    Science.gov (United States)

    Chen, Qian; Ma, Jian-Xing

    2017-10-01

    Diabetic retinopathy (DR) is a common eye complication of diabetes, and the pathogenic mechanism of DR is still under investigation. The canonical Wnt signaling pathway is an evolutionarily conserved pathway that plays fundamental roles in embryogenesis and adult tissue homeostasis. Wnt signaling regulates expression of multiple genes that control retinal development and eye organogenesis, and dysregulated Wnt signaling plays pathophysiological roles in many ocular diseases, including DR. This review highlights recent progress in studies of Wnt signaling in DR. We discuss Wnt signaling regulation in the retina and dysregulation of Wnt signaling associated with ocular diseases with an emphasis on DR. We also discuss the therapeutic potential of modulating Wnt signaling in DR. Continued studies in this field will advance our current understanding on DR and contribute to the development of new treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Reference: 408 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available o T et al. 2006 Aug. Plant J. 47(4):619-28. Plants can sense the direction of gravity and change the growth ...orientation of their organs. To elucidate the molecular mechanisms of gravity perception and the signal tran...SGR5 promoter revealed that SGR5 is mainly expressed in the endodermis, the gravity-sensing tissue in inflor...f SGR5 using the SCR promoter in the sgr5-1 mutant restores shoot gravitropism indicates that it could function in the gravity...st all amyloplasts in the endodermal cells of the sgr5-1 mutant sedimented in the direction of gravity. Take

  5. AREVA - 2012 Reference document

    International Nuclear Information System (INIS)

    2013-03-01

    After a presentation of the person responsible for this Reference Document, of statutory auditors, and of a summary of financial information, this report address the different risk factors: risk management and coverage, legal risk, industrial and environmental risk, operational risk, risk related to major projects, liquidity and market risk, and other risks (related to political and economic conditions, to Group's structure, and to human resources). The next parts propose information about the issuer, a business overview (markets for nuclear power and renewable energies, customers and suppliers, group's strategy, operations), a brief presentation of the organizational structure, a presentation of properties, plants and equipment (principal sites, environmental issues which may affect these items), analysis and comments on the group's financial position and performance, a presentation of capital resources, a presentation of research and development activities (programs, patents and licenses), a brief description of financial objectives and profit forecasts or estimates, a presentation of administration, management and supervision bodies, a description of the operation of corporate bodies, an overview of personnel, of principal shareholders, and of transactions with related parties, a more detailed presentation of financial information concerning assets, financial positions and financial performance. Addition information regarding share capital is given, as well as an indication of major contracts, third party information, available documents, and information on holdings

  6. Reference thorium fuel cycle

    International Nuclear Information System (INIS)

    Driggers, F.E.

    1978-08-01

    In the reference fuel cycle for the TFCT program, fissile U will be denatured by mixing with 238 U; the plants will be located in secure areas, with Pu being recycled within these secure areas; Th will be recycled with recovered U and Pu; the head end will handle a variety of core and blanket fuel assembly designs for LWRs and HWRs; the fuel may be a homogeneous mixture either of U and Th oxide pellets or sol-gel microspheres; the cladding will be Zircaloy; and MgO may be added to the fuel to improve Th dissolution. Th is being considered as the fertile component of fuel in order to increase proliferation resistance. Spent U recovered from Th-based fuels must be re-enriched before recycle to prevent very rapid buildup of 238 U. Stainless steel will be considered as a backup to Zircaloy cladding in case Zr is incompatible with commercial aqueous dissolution. Storage of recovered irradiated Th will be considered as a backup to its use in the recycle of recovered Pu and U. Estimates are made of the time for introducing the Th fuel cycle into the LWR power industry. Since U fuel exposures in LWRs are likely to increase from 30,000 to 50,000 MWD/MT, the Th reprocessing plant should also be designed for Th fuel with 50,000 MWD/MT exposure

  7. Sensor Characteristics Reference Guide

    Energy Technology Data Exchange (ETDEWEB)

    Cree, Johnathan V.; Dansu, A.; Fuhr, P.; Lanzisera, Steven M.; McIntyre, T.; Muehleisen, Ralph T.; Starke, M.; Banerjee, Pranab; Kuruganti, T.; Castello, C.

    2013-04-01

    The Buildings Technologies Office (BTO), within the U.S. Department of Energy (DOE), Office of Energy Efficiency and Renewable Energy (EERE), is initiating a new program in Sensor and Controls. The vision of this program is: • Buildings operating automatically and continuously at peak energy efficiency over their lifetimes and interoperating effectively with the electric power grid. • Buildings that are self-configuring, self-commissioning, self-learning, self-diagnosing, self-healing, and self-transacting to enable continuous peak performance. • Lower overall building operating costs and higher asset valuation. The overarching goal is to capture 30% energy savings by enhanced management of energy consuming assets and systems through development of cost-effective sensors and controls. One step in achieving this vision is the publication of this Sensor Characteristics Reference Guide. The purpose of the guide is to inform building owners and operators of the current status, capabilities, and limitations of sensor technologies. It is hoped that this guide will aid in the design and procurement process and result in successful implementation of building sensor and control systems. DOE will also use this guide to identify research priorities, develop future specifications for potential market adoption, and provide market clarity through unbiased information

  8. Uranium tailings reference materials

    International Nuclear Information System (INIS)

    Smith, C.W.; Steger, H.F.; Bowman, W.S.

    1984-01-01

    Samples of uranium tailings from Bancroft and Elliot Lake, Ontario, and from Beaverlodge and Rabbit Lake, Saskatchewan, have been prepared as compositional reference materials at the request of the National Uranium Tailings Research Program. The four samples, UTS-1 to UTS-4, were ground to minus 104 μm, each mixed in one lot and bottled in 200-g units for UTS-1 to UTS-3 and in 100-g units for UTS-4. The materials were tested for homogeneity with respect to uranium by neutron activation analysis and to iron by an acid-decomposition atomic absorption procedure. In a free choice analytical program, 18 laboratories contributed results for one or more of total iron, titanium, aluminum, calcium, barium, uranium, thorium, total sulphur, and sulphate for all four samples, and for nickel and arsenic in UTS-4 only. Based on a statistical analysis of the data, recommended values were assigned to all elements/constituents, except for sulphate in UTS-3 and nickel in UTS-4. The radioactivity of thorium-230, radium-226, lead-210, and polonium-210 in UTS-1 to UTS-4 and of thorium-232, radium-228, and thorium-228 in UTS-1 and UTS-2 was determined in a radioanalytical program composed of eight laboratories. Recommended values for the radioactivities and associated parameters were calculated by a statistical treatment of the results

  9. Tissue bionics: examples in biomimetic tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Green, David W [Bone and Joint Research Group, Developmental Origins of Health and Disease, General Hospital, University of Southampton, SO16 6YD (United Kingdom)], E-mail: Hindoostuart@googlemail.com

    2008-09-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

  10. Tissue bionics: examples in biomimetic tissue engineering

    International Nuclear Information System (INIS)

    Green, David W

    2008-01-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic

  11. TAM receptor signaling in development.

    Science.gov (United States)

    Burstyn-Cohen, Tal

    2017-01-01

    TYRO3, AXL and MERTK comprise the TAM family of receptor protein tyrosine kinases. Activated by their ligands, protein S (PROS1) and growth-arrest-specific 6 (GAS6), they mediate numerous cellular functions throughout development and adulthood. Expressed by a myriad of cell types and tissues, they have been implicated in homeostatic regulation of the immune, nervous, vascular, bone and reproductive systems. The loss-of-function of TAM signaling in adult tissues culminates in the destruction of tissue homeostasis and diseased states, while TAM gain-of-function in various tumors promotes cancer phenotypes. Combinatorial ligand-receptor interactions may elicit different molecular and cellular responses. Many of the TAM regulatory functions are essentially developmental, taking place both during embryogenesis and postnatally. This review highlights current knowledge on the role of TAM receptors and their ligands during these developmental processes in the immune, nervous, vascular and reproductive systems.

  12. ENRAF gauge reference level calculations

    Energy Technology Data Exchange (ETDEWEB)

    Huber, J.H., Fluor Daniel Hanford

    1997-02-06

    This document describes the method for calculating reference levels for Enraf Series 854 Level Detectors as installed in the tank farms. The reference level calculation for each installed level gauge is contained herein.

  13. Global Reference Tables Services Architecture

    Data.gov (United States)

    Social Security Administration — This database stores the reference and transactional data used to provide a data-driven service access method to certain Global Reference Table (GRT) service tables.

  14. Genetics Home Reference: PURA syndrome

    Science.gov (United States)

    ... TJ, Vreeburg M, Rouhl RPW, Stevens SJC, Stegmann APA, Schieving J, Pfundt R, van Dijk K, Smeets ... article on PubMed Central More from Genetics Home Reference Bulletins Genetics Home Reference Celebrates Its 15th Anniversary ...

  15. Adipose tissue as an endocrine organ.

    Science.gov (United States)

    McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

    2014-02-01

    Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Areva - 2014 Reference document

    International Nuclear Information System (INIS)

    2015-01-01

    Areva supplies high added-value products and services to support the operation of the global nuclear fleet. The company is present throughout the entire nuclear cycle, from uranium mining to used fuel recycling, including nuclear reactor design and operating services. Areva is recognized by utilities around the world for its expertise, its skills in cutting-edge technologies and its dedication to the highest level of safety. Areva's 44,000 employees are helping build tomorrow's energy model: supplying ever safer, cleaner and more economical energy to the greatest number of people. This Reference Document contains information on Areva's objectives, prospects and development strategies. It contains estimates of the markets, market shares and competitive position of Areva. Contents: 1 - Person responsible; 2 - Statutory auditors; 3 - Selected financial information; 4 - Risk factors; 5 - Information about the issuer; 6 - Business overview; 7 - Organizational structure; 8 - Property, plant and equipment; 9 - Analysis of and comments on the group's financial position and performance; 10 - Capital resources; 11 - Research and development programs, patents and licenses; 12 - Trend information; 13 - Profit forecasts; 14 - Administrative, management and supervisory bodies and senior management; 15 - Compensation and benefits; 16 - Functioning of administrative, management and supervisory bodies and senior management; 17 - Employees; 18 - Principal shareholders; 19 - Transactions with related parties; 20 - Financial information concerning assets, financial positions and financial performance; 21 - Additional information; 22 - Major contracts; 23 - Third party information, statements by experts and declarations of interest; 24 - Documents on display; 25 - information on holdings; appendix: Report of the Chairman of the Board of Directors on governance, internal control procedures and risk management, Statutory Auditors' report, Corporate social

  17. Biased and g protein-independent signaling of chemokine receptors

    DEFF Research Database (Denmark)

    Steen, Anne; Larsen, Olav; Thiele, Stefanie

    2014-01-01

    ), different receptors (with the same ligand), or different tissues or cells (for the same ligand-receptor pair). Most often biased signaling is differentiated into G protein-dependent and β-arrestin-dependent signaling. Yet, it may also cover signaling differences within these groups. Moreover, it may...

  18. Imaging in cellular and tissue engineering

    CERN Document Server

    Yu, Hanry

    2013-01-01

    Details on specific imaging modalities for different cellular and tissue engineering applications are scattered throughout articles and chapters in the literature. Gathering this information into a single reference, Imaging in Cellular and Tissue Engineering presents both the fundamentals and state of the art in imaging methods, approaches, and applications in regenerative medicine. The book underscores the broadening scope of imaging applications in cellular and tissue engineering. It covers a wide range of optical and biological applications, including the repair or replacement of whole tiss

  19. Cellular semiotics and signal transduction

    DEFF Research Database (Denmark)

    Bruni, Luis Emilio

    2007-01-01

    Semiosis, the processes of production, communication and interpretation of signs - coding and de-coding - takes place within and between organisms. The term "endosemiosis" refers to the processes of interpretation and sign transmission inside an organism (as opposed to "exosemiosis", which refers...... to the processes of sign interpretation and transmission between organisms of the same or different species). In Biosemiotics it is customary to recognise the cell as the most elementary integration unit for semiosis. Therefore intra and intercellular communication constitute the departure point for the study...... considering semiotic logic in order to construct our understanding of living phenomena. Given the central integrating role of signal transduction in physiological and ecological studies, this chapter outlines its semiotic implications. The multi-modality and modularity of signal molecules and relative...

  20. Metabolites in vertebrate Hedgehog signaling.

    Science.gov (United States)

    Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

    2014-04-11

    The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Kerlinger's Criterial Referents Theory Revisited.

    Science.gov (United States)

    Zak, Itai; Birenbaum, Menucha

    1980-01-01

    Kerlinger's criterial referents theory of attitudes was tested cross-culturally by administering an education attitude referents summated-rating scale to 713 individuals in Israel. The response pattern to criterial and noncriterial referents was examined. Results indicated empirical cross-cultural validity of theory, but questioned measuring…

  2. Fundamentals of Managing Reference Collections

    Science.gov (United States)

    Singer, Carol A.

    2012-01-01

    Whether a library's reference collection is large or small, it needs constant attention. Singer's book offers information and insight on best practices for reference collection management, no matter the size, and shows why managing without a plan is a recipe for clutter and confusion. In this very practical guide, reference librarians will learn:…

  3. Knowledge Management and Reference Services

    Science.gov (United States)

    Gandhi, Smiti

    2004-01-01

    Many corporations are embracing knowledge management (KM) to capture the intellectual capital of their employees. This article focuses on KM applications for reference work in libraries. It defines key concepts of KM, establishes a need for KM for reference services, and reviews various KM initiatives for reference services.

  4. Polyploidization in liver tissue.

    Science.gov (United States)

    Gentric, Géraldine; Desdouets, Chantal

    2014-02-01

    Polyploidy (alias whole genome amplification) refers to organisms containing more than two basic sets of chromosomes. Polyploidy was first observed in plants more than a century ago, and it is known that such processes occur in many eukaryotes under a variety of circumstances. In mammals, the development of polyploid cells can contribute to tissue differentiation and, therefore, possibly a gain of function; alternately, it can be associated with development of disease, such as cancer. Polyploidy can occur because of cell fusion or abnormal cell division (endoreplication, mitotic slippage, or cytokinesis failure). Polyploidy is a common characteristic of the mammalian liver. Polyploidization occurs mainly during liver development, but also in adults with increasing age or because of cellular stress (eg, surgical resection, toxic exposure, or viral infections). This review will explore the mechanisms that lead to the development of polyploid cells, our current state of understanding of how polyploidization is regulated during liver growth, and its consequence on liver function. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  5. The neural correlates of reference to the past

    Directory of Open Access Journals (Sweden)

    Laura S. Bos

    2014-04-01

    Analysis (see Figure 1 showed greater BOLD signal change for both types of past over non-past time-reference bilaterally frontal—the SMA and frontal superior medial gyrus. We ascribe this to increased difficulty in selecting past time-reference inflection, hence, discourse linking. We found significantly increased LIFG activation for simple past over simple present, but not for periphrastic past over future (see Figure 1C. LIFG might be taxed for past tense inflection, but not past time-reference specifically. Although periphrastic past and future differ in time-reference, both verb clusters have a present tense auxiliary. Our results align with a fundamental difference between past and non-past time-reference, and are in accordance with past time-reference processing difficulties of aphasic individuals.

  6. Microfabricated Reference Electrodes and their Biosensing Applications

    Directory of Open Access Journals (Sweden)

    M. Jamal Deen

    2010-03-01

    Full Text Available Over the past two decades, there has been an increasing trend towards miniaturization of both biological and chemical sensors and their integration with miniaturized sample pre-processing and analysis systems. These miniaturized lab-on-chip devices have several functional advantages including low cost, their ability to analyze smaller samples, faster analysis time, suitability for automation, and increased reliability and repeatability. Electrical based sensing methods that transduce biological or chemical signals into the electrical domain are a dominant part of the lab-on-chip devices. A vital part of any electrochemical sensing system is the reference electrode, which is a probe that is capable of measuring the potential on the solution side of an electrochemical interface. Research on miniaturization of this crucial component and analysis of the parameters that affect its performance, stability and lifetime, is sparse. In this paper, we present the basic electrochemistry and thermodynamics of these reference electrodes and illustrate the uses of reference electrodes in electrochemical and biological measurements. Different electrochemical systems that are used as reference electrodes will be presented, and an overview of some contemporary advances in electrode miniaturization and their performance will be provided.

  7. Aloe Vera for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Shekh Rahman

    2017-02-01

    Full Text Available Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers.

  8. Aloe Vera for Tissue Engineering Applications.

    Science.gov (United States)

    Rahman, Shekh; Carter, Princeton; Bhattarai, Narayan

    2017-02-14

    Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers.

  9. Tissue polarimetry: concepts, challenges, applications, and outlook.

    Science.gov (United States)

    Ghosh, Nirmalya; Vitkin, I Alex

    2011-11-01

    Polarimetry has a long and successful history in various forms of clear media. Driven by their biomedical potential, the use of the polarimetric approaches for biological tissue assessment has also recently received considerable attention. Specifically, polarization can be used as an effective tool to discriminate against multiply scattered light (acting as a gating mechanism) in order to enhance contrast and to improve tissue imaging resolution. Moreover, the intrinsic tissue polarimetry characteristics contain a wealth of morphological and functional information of potential biomedical importance. However, in a complex random medium-like tissue, numerous complexities due to multiple scattering and simultaneous occurrences of many scattering and polarization events present formidable challenges both in terms of accurate measurements and in terms of analysis of the tissue polarimetry signal. In order to realize the potential of the polarimetric approaches for tissue imaging and characterization/diagnosis, a number of researchers are thus pursuing innovative solutions to these challenges. In this review paper, we summarize these and other issues pertinent to the polarized light methodologies in tissues. Specifically, we discuss polarized light basics, Stokes-Muller formalism, methods of polarization measurements, polarized light modeling in turbid media, applications to tissue imaging, inverse analysis for polarimetric results quantification, applications to quantitative tissue assessment, etc.

  10. Radar signal processing and its applications

    CERN Document Server

    Hummel, Robert; Stoica, Petre; Zelnio, Edmund

    2003-01-01

    Radar Signal Processing and Its Applications brings together in one place important contributions and up-to-date research results in this fast-moving area. In twelve selected chapters, it describes the latest advances in architectures, design methods, and applications of radar signal processing. The contributors to this work were selected from the leading researchers and practitioners in the field. This work, originally published as Volume 14, Numbers 1-3 of the journal, Multidimensional Systems and Signal Processing, will be valuable to anyone working or researching in the field of radar signal processing. It serves as an excellent reference, providing insight into some of the most challenging issues being examined today.

  11. Astrocytes in endocannabinoid signalling.

    Science.gov (United States)

    Navarrete, Marta; Díez, Adolfo; Araque, Alfonso

    2014-10-19

    Astrocytes are emerging as integral functional components of synapses, responding to synaptically released neurotransmitters and regulating synaptic transmission and plasticity. Thus, they functionally interact with neurons establishing tripartite synapses: a functional concept that refers to the existence of communication between astrocytes and neurons and its crucial role in synaptic function. Here, we discuss recent evidence showing that astrocytes are involved in the endocannabinoid (ECB) system, responding to exogenous cannabinoids as well as ECBs through activation of type 1 cannabinoid receptors, which increase intracellular calcium and stimulate the release of glutamate that modulates synaptic transmission and plasticity. We also discuss the consequences of ECB signalling in tripartite synapses on the astrocyte-mediated regulation of synaptic function, which reveal novel properties of synaptic regulation by ECBs, such as the spatially controlled dual effect on synaptic strength and the lateral potentiation of synaptic efficacy. Finally, we discuss the potential implications of ECB signalling for astrocytes in brain pathology and animal behaviour. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  12. Fast digitizing and digital signal processing of detector signals

    International Nuclear Information System (INIS)

    Hannaske, Roland

    2008-01-01

    A fast-digitizer data acquisition system recently installed at the neutron time-of-flight experiment nELBE, which is located at the superconducting electron accelerator ELBE of Forschungszentrum Dresden-Rossendorf, is tested with two different detector types. Preamplifier signals from a high-purity germanium detector are digitized, stored and finally processed. For a precise determination of the energy of the detected radiation, the moving-window deconvolution algorithm is used to compensate the ballistic deficit and different shaping algorithms are applied. The energy resolution is determined in an experiment with γ-rays from a 22 Na source and is compared to the energy resolution achieved with analogously processed signals. On the other hand, signals from the photomultipliers of barium fluoride and plastic scintillation detectors are digitized. These signals have risetimes of a few nanoseconds only. The moment of interaction of the radiation with the detector is determined by methods of digital signal processing. Therefore, different timing algorithms are implemented and tested with data from an experiment at nELBE. The time resolutions achieved with these algorithms are compared to each other as well as to reference values coming from analog signal processing. In addition to these experiments, some properties of the digitizing hardware are measured and a program for the analysis of stored, digitized data is developed. The analysis of the signals shows that the energy resolution achieved with the 10-bit digitizer system used here is not competitive to a 14-bit peak-sensing ADC, although the ballistic deficit can be fully corrected. However, digital methods give better result in sub-ns timing than analog signal processing. (orig.)

  13. Nuclear magnetic resonance of perfused tissue

    International Nuclear Information System (INIS)

    Harpen, M.D.; Allison, R.C.

    1986-01-01

    The effect of perfusion on the NMR signal observed in NMR imaging is studied in a phantom and in two isolated perfused canine lungs. It is observed that perfusion in tissue has little effect on longitudinal relaxation times. Transverse relaxation rates are observed to correlate linearly with rates of perfusion, in accordance with a model presented. (author)

  14. Age dependence of spleen- and muscle-corrected hepatic signal enhancement on hepatobiliary phase gadoxetate MRI

    Energy Technology Data Exchange (ETDEWEB)

    Matoori, Simon [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Hirslanden Clinic St. Anna, Clinical Research Group, Lucerne (Switzerland); Froehlich, Johannes M. [Hirslanden Clinic St. Anna, Clinical Research Group, Lucerne (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Zurich (Switzerland); Cantonal Hospital Winterthur, Department of Radiology, Winterthur (Switzerland); Breitenstein, Stefan [Cantonal Hospital Winterthur, Department of Surgery, Clinic for Visceral and Thoracic Surgery, Winterthur (Switzerland); Doert, Aleksis [Cantonal Hospital Winterthur, Department of Radiology, Winterthur (Switzerland); Pozdniakova, Viktoria [Stavanger University Hospital, Department of Radiology, Stavanger (Norway); Koh, Dow-Mu [Royal Marsden Hospital, Department of Radiology, Surrey, England (United Kingdom); Gutzeit, Andreas [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Hirslanden Clinic St. Anna, Clinical Research Group, Lucerne (Switzerland); Cantonal Hospital Winterthur, Department of Radiology, Winterthur (Switzerland)

    2016-06-15

    To identify correlations of signal enhancements (SE) and SE normalized to reference tissues of the spleen, kidney, liver, musculus erector spinae (MES) and ductus hepatocholedochus (DHC) on hepatobiliary phase gadoxetate-enhanced MRI with patient age in non-cirrhotic patients. A heterogeneous cohort of 131 patients with different clinical backgrounds underwent a standardized 3.0-T gadoxetate-enhanced liver MRI between November 2008 and June 2013. After exclusion of cirrhotic patients, a cohort of 75 patients with no diagnosed diffuse liver disease was selected. The ratio of signal intensity 20 min post- to pre-contrast administration (SE) in the spleen, kidney, liver, MES and DHC, and the SE of the kidney, liver and DHC normalized to the reference tissues spleen or MES were compared to patient age. Patient age was inversely correlated with the liver SE normalized to the spleen and MES SE (both p < 0.001) and proportionally with the SE of the spleen (p = 0.043), the MES (p = 0.030) and the kidney (p = 0.022). No significant correlations were observed for the DHC (p = 0.347) and liver SE (p = 0.606). The age dependence of hepatic SE normalized to the enhancement in the spleen and MES calls for a cautious interpretation of these quantification methods. (orig.)

  15. Age dependence of spleen- and muscle-corrected hepatic signal enhancement on hepatobiliary phase gadoxetate MRI

    International Nuclear Information System (INIS)

    Matoori, Simon; Froehlich, Johannes M.; Breitenstein, Stefan; Doert, Aleksis; Pozdniakova, Viktoria; Koh, Dow-Mu; Gutzeit, Andreas

    2016-01-01

    To identify correlations of signal enhancements (SE) and SE normalized to reference tissues of the spleen, kidney, liver, musculus erector spinae (MES) and ductus hepatocholedochus (DHC) on hepatobiliary phase gadoxetate-enhanced MRI with patient age in non-cirrhotic patients. A heterogeneous cohort of 131 patients with different clinical backgrounds underwent a standardized 3.0-T gadoxetate-enhanced liver MRI between November 2008 and June 2013. After exclusion of cirrhotic patients, a cohort of 75 patients with no diagnosed diffuse liver disease was selected. The ratio of signal intensity 20 min post- to pre-contrast administration (SE) in the spleen, kidney, liver, MES and DHC, and the SE of the kidney, liver and DHC normalized to the reference tissues spleen or MES were compared to patient age. Patient age was inversely correlated with the liver SE normalized to the spleen and MES SE (both p < 0.001) and proportionally with the SE of the spleen (p = 0.043), the MES (p = 0.030) and the kidney (p = 0.022). No significant correlations were observed for the DHC (p = 0.347) and liver SE (p = 0.606). The age dependence of hepatic SE normalized to the enhancement in the spleen and MES calls for a cautious interpretation of these quantification methods. (orig.)

  16. Lipid signaling in adipose tissue: Connecting inflammation & metabolism

    Czech Academy of Sciences Publication Activity Database

    Masoodi, M.; Kuda, Ondřej; Rossmeisl, Martin; Flachs, Pavel; Kopecký, Jan

    2015-01-01

    Roč. 1851, č. 4 (2015), s. 503-518 ISSN 1388-1981 R&D Projects: GA ČR(CZ) GA13-00871S; GA MŠk(CZ) 7E12073; GA MŠk(CZ) LH14040 Institutional support: RVO:67985823 Keywords : adipocyte * futile substrate cycle * macrophage Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.779, year: 2015

  17. Fluorescence in situ hybridization on formalin-fixed and paraffin-embedded tissue

    DEFF Research Database (Denmark)

    Laub Petersen, Bodil; Zeuthen, Mette Christa; Pedersen, Sanni

    2004-01-01

    , such as quantitation of signals as in triploidy, it is possible to isolate nuclei from paraffin-embedded tissue. However, using formalin-fixed paraffin-embedded tissue, either in thin sections or as isolated nuclei, one encounters a range of technical problems, paralleling those met in immunohistochemistry. Variations...... nuclei and tissue sections from formalin-fixed, paraffin-embedded tissue....

  18. Esophageal tissue engineering: A new approach for esophageal replacement

    Institute of Scientific and Technical Information of China (English)

    Giorgia Totonelli; Panagiotis Maghsoudlou; Jonathan M Fishman; Giuseppe Orlando; Tahera Ansari; Paul Sibbons; Martin A Birchall

    2012-01-01

    A number of congenital and acquired disorders require esophageal tissue replacement.Various surgical techniques,such as gastric and colonic interposition,are standards of treatment,but frequently complicated by stenosis and other problems.Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function.We review the literature of esophageal tissue engineering,discuss its implications,compare the methodologies that have been employed and suggest possible directions for the future.Medline,Embase,the Cochrane Library,National Research Register and ClinicalTrials.gov databases were searched with the following search terms:stem cell and esophagus,esophageal replacement,esophageal tissue engineering,esophageal substitution.Reference lists of papers identified were also examined and experts in this field contacted for further information.All full-text articles in English of all potentially relevant abstracts were reviewed.Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation.When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality.Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration,whilst omental wrapping to induce vascularization of the construct has an uncertain benefit.Decellularized matrices have been recently suggested as the optimal choice for scaffolds,but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution.Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a

  19. Extracellular vesicles provide a means for tissue crosstalk during exercise

    DEFF Research Database (Denmark)

    Whitham, Martin; Parker, Benjamin L; Friedrichsen, Martin

    2018-01-01

    Exercise stimulates the release of molecules into the circulation, supporting the concept that inter-tissue signaling proteins are important mediators of adaptations to exercise. Recognizing that many circulating proteins are packaged in extracellular vesicles (EVs), we employed quantitative prot...

  20. Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration

    DEFF Research Database (Denmark)

    Ohki, Makiko; Ohki, Yuichi; Ishihara, Makoto

    2010-01-01

    tissue regeneration is not well understood. Bone marrow (BM)-derived myeloid cells facilitate angiogenesis during tissue regeneration. Here, we report that a serpin-resistant form of tPA by activating the extracellular proteases matrix metalloproteinase-9 and plasmin expands the myeloid cell pool......-A. Remarkably, transplantation of BM-derived tPA-mobilized CD11b(+) cells and VEGFR-1(+) cells, but not carrier-mobilized cells or CD11b(-) cells, accelerates neovascularization and ischemic tissue regeneration. Inhibition of VEGF signaling suppresses tPA-induced neovascularization in a model of hind limb...... and mobilizes CD45(+)CD11b(+) proangiogenic, myeloid cells, a process dependent on vascular endothelial growth factor-A (VEGF-A) and Kit ligand signaling. tPA improves the incorporation of CD11b(+) cells into ischemic tissues and increases expression of neoangiogenesis-related genes, including VEGF...