Science.gov

Sample records for early cellular effects

  1. [Effect of early high fat diet on pancreatic β cellularity and insulin sensibility in young rats].

    PubMed

    Xie, Kun-Xia; Xiao, Yan-Feng; Xu, Er-Di; Yin, Chun-Yan; Yi, Xiao-Qing; Chang, Ming

    2010-09-01

    To study the effects of early high fat diet on sugar metaboliam, insulin sensibility and pancreatic β cellularity in young rats. Sixty male weaned young rats were randomly fed with high fat diet (high fat group) and normal diet (control group). The body weight, viscus fattiness and fasting plasma glucose (FPG) were measured after 3, 6 and 9 weeks. Serum insulin level was measured with radioimmunoassay. The ultrastructure of pancreas was observed under an electricmicroscope. The high fat group had significantly higher body weight and visceral fat weight than the control group after 3 weeks. There were no significant differences in the FPG level between the two groups at all time points. The levels of fasting insulin and HOMAIR in the high fat group were significantly higher than those in the control group after 3, 6 and 9 weeks (P<0.01). Dilation of rough endoplasmic reticulum and mild swelling of mitochondria of islet β-cells were observed in the high fat group after 6 weeks. Early high fat diet may induce a reduction in insulin sensitivity and produce insulin resistance in young rats. Endoplasmic reticulum expansion in β-cells may be an early sign of β-cell damage due to obesity.

  2. The effect of human hair keratin hydrogel on early cellular response to sciatic nerve injury in a rat model.

    PubMed

    Pace, Lauren A; Plate, Johannes F; Smith, Thomas L; Van Dyke, Mark E

    2013-08-01

    Peripheral nerve injuries requiring surgery can be repaired by autograft, the clinical "gold standard", allograft, or nerve conduits. Most published clinical studies show the effectiveness of nerve conduits in small size defects in sensory nerves. Many preclinical studies suggest that peripheral nerve regeneration through conduits can be enhanced and repair lengths increased with the use of a biomaterial filler in the conduit lumen. We have previously shown that a luminal hydrogel filler derived from human hair keratin (HHK) can improve electrophysiological and histological outcomes in mouse, rabbit, and non-human primate nerve injury models, but insight into potential mechanisms has been lacking. Based on the premise that a keratin biomaterial (KOS) hydrogel provides an instantaneous structural matrix within the lumen, the current study compares the cellular behavior elicited by KOS hydrogel to Matrigel (MAT) and saline (SAL) conduit fillers in a 1 cm rat sciatic nerve injury model at early stages of regeneration. While there was little difference in initial cellular influx, the KOS group showed earlier migration of dedifferentiated Schwann cells (SC) from the proximal nerve end compared to the other groups. The KOS group also showed faster SC dedifferentiation and myelin debris clearance, and decreased macrophage infiltration during Wallerian degeneration of the distal nerve tissue. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Early Effects of Salinity on Water Transport in Arabidopsis Roots. Molecular and Cellular Features of Aquaporin Expression1

    PubMed Central

    Boursiac, Yann; Chen, Sheng; Luu, Doan-Trung; Sorieul, Mathias; van den Dries, Niels; Maurel, Christophe

    2005-01-01

    Aquaporins facilitate the uptake of soil water and mediate the regulation of root hydraulic conductivity (Lpr) in response to a large variety of environmental stresses. Here, we use Arabidopsis (Arabidopsis thaliana) plants to dissect the effects of salt on both Lpr and aquaporin expression and investigate possible molecular and cellular mechanisms of aquaporin regulation in plant roots under stress. Treatment of plants by 100 mm NaCl was perceived as an osmotic stimulus and induced a rapid (half-time, 45 min) and significant (70%) decrease in Lpr, which was maintained for at least 24 h. Macroarray experiments with gene-specific tags were performed to investigate the expression of all 35 genes of the Arabidopsis aquaporin family. Transcripts from 20 individual aquaporin genes, most of which encoded members of the plasma membrane intrinsic protein (PIP) and tonoplast intrinsic protein (TIP) subfamilies, were detected in nontreated roots. All PIP and TIP aquaporin transcripts with a strong expression signal showed a 60% to 75% decrease in their abundance between 2 and 4 h following exposure to salt. The use of antipeptide antibodies that cross-reacted with isoforms of specific aquaporin subclasses revealed that the abundance of PIP1s decreased by 40% as early as 30 min after salt exposure, whereas PIP2 and TIP1 homologs showed a 20% to 40% decrease in abundance after 6 h of treatment. Expression in transgenic plants of aquaporins fused to the green fluorescent protein revealed that the subcellular localization of TIP2;1 and PIP1 and PIP2 homologs was unchanged after 45 min of exposure to salt, whereas a TIP1;1-green fluorescent protein fusion was relocalized into intracellular spherical structures tentatively identified as intravacuolar invaginations. The appearance of intracellular structures containing PIP1 and PIP2 homologs was occasionally observed after 2 h of salt treatment. In conclusion, this work shows that exposure of roots to salt induces changes in

  4. Cellular mechanisms underlying an effect of "early handling" on pCREB and BDNF in the neonatal rat hippocampus.

    PubMed

    Garoflos, Efstathios; Stamatakis, Antonios; Mantelas, Athanasios; Philippidis, Helen; Stylianopoulou, Fotini

    2005-08-09

    Early experiences have long-term effects on brain function and behavior. However, the precise mechanisms involved still remain elusive. In an effort to address this issue, we employed the model of "early handling", which is known to affect the ability of the adult organism to respond to stressful stimuli, and determined its effects on hippocampal pCREB and BDNF 2, 4, and 8 h later. 8 h following "handling" on postnatal day 1, there was an increase in pCREB and BDNF positive cells in the hippocampus, a brain area which is a specific target of "handling". On the other hand, vehicle injection resulted in decreased pCREB and BDNF in both handled and non-handled animals 2 and 4 h later. The "handling"-induced increase of pCREB and BDNF was cancelled by inhibition of NMDA, AMPA/kainate, GABA-A, 5-HT1A or 5-HT2A/C receptors, as well as L-type voltage-gated Ca(2+) channels. It thus appears that "early handling" activates these neurotransmitter receptors, leading to increased intracellular Ca(2+), phosphorylation of the transcription factor CREB, and increased BDNF expression. BDNF can then exert its morphogenetic effects and thus "imprint" the effects of "handling" on the brain.

  5. Molecular and cellular effects of chemicals disrupting steroidogenesis during early ovarian development of brown trout (Salmo trutta fario).

    PubMed

    a Marca Pereira, M L; Eppler, E; Thorpe, K L; Wheeler, J R; Burkhardt-Holm, P

    2014-02-01

    A range of chemicals found in the aquatic environment have the potential to influence endocrine function and affect sexual development by mimicking or antagonizing the effects of hormones, or by altering the synthesis and metabolism of hormones. The aim of this study was to evaluate whether the effects of chemicals interfering with sex hormone synthesis may affect the regulation of early ovarian development via the modulation of sex steroid and insulin-like growth factor (IGF) systems. To this end, ex vivo ovary cultures of juvenile brown trout (Salmo trutta fario) were exposed for 2 days to either 1,4,6-androstatriene-3,17-dione (ATD, a specific aromatase inhibitor), prochloraz (an imidazole fungicide), or tributyltin (TBT, a persistent organic pollutant). Further, juvenile female brown trout were exposed in vivo for 2 days to prochloraz or TBT. The ex vivo and in vivo ovarian gene expression of the aromatase (CYP19), responsible for estrogen production, and of IGF1 and 2 were compared. Moreover, 17β-estradiol (E2) and testosterone (T) production from ex vivo ovary cultures was assessed. Ex vivo exposure to ATD inhibited ovarian E2 synthesis, while T levels accumulated. However, ATD did not affect ex vivo expression of cyp19, igf1, or igf2. Ex vivo exposure to prochloraz inhibited ovarian E2 production, but did not affect T levels. Further prochloraz up-regulated igf1 expression in both ex vivo and in vivo exposures. TBT exposure did not modify ex vivo synthesis of either E2 or T. However, in vivo exposure to TBT down-regulated igf2 expression. The results indicate that ovarian inhibition of E2 production in juvenile brown trout might not directly affect cyp19 and igf gene expression. Thus, we suggest that the test chemicals may interfere with both sex steroid and IGF systems in an independent manner, and based on published literature, potentially lead to endocrine dysfunction and altered sexual development. Copyright © 2011 Wiley Periodicals, Inc., A Wiley

  6. Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR.

    PubMed

    Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

    2015-08-01

    Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue.

  7. Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR

    PubMed Central

    Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

    2015-01-01

    Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue. PMID:26171232

  8. Cellular mechanism underlying hypothermia-induced ventricular tachycardia/ventricular fibrillation in the setting of early repolarization and the protective effect of quinidine, cilostazol, and milrinone.

    PubMed

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V; Antzelevitch, Charles

    2014-02-01

    Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome and examines the effectiveness of quinidine, cilostazol, and milrinone to prevent hypothermia-induced arrhythmias. Transmembrane action potentials were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3-10 μmol/L) and verapamil (1 μmol/L) was used to pharmacologically model the genetic mutations responsible for ER syndrome. Acetylcholine (3 μmol/L) was used to simulate increased parasympathetic tone, which is known to promote ER. In controls, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J-wave area on the ECG and accentuated epicardial action potential notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial action potential notch, leading to loss of the action potential dome at some sites but not others, thus creating the substrate for development of phase 2 reentry and VT/VF. Addition of the transient outward current antagonist quinidine (5 μmol/L) or the phosphodiesterase III inhibitors cilostazol (10 μmol/L) or milrinone (5 μmol/L) diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase 2 reentry. Quinidine, cilostazol, and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities.

  9. Cellular Mechanism Underlying Hypothermia-Induced VT/VF in the Setting of Early Repolarization and the Protective Effect of Quinidine, Cilostazol and Milrinone

    PubMed Central

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V.; Antzelevitch, Charles

    2014-01-01

    Background Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome (ERS) and examines the effectiveness of quinidine, cilostazol and milrinone to prevent hypothermia-induced arrhythmias. Method and Results Transmembrane action potentials (AP) were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left-ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3–10 µM) and verapamil (1µM) was used to pharmacologically model the genetic mutations responsible for ERS. Acetylcholine (3µM) was used to simulate increased parasympathetic tone, which is known to promote ER. In control, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J wave area on the ECG and accentuated epicardial AP notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial AP notch, leading to loss of the AP dome at some sites but not others, thus creating the substrate for development of phase-2-reentry and VT/VF. Addition of the Ito antagonist quinidine (5 µM) or the phosphodiesterase III inhibitors cilostazol (10 µM) or milrinone (5 µM), diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Conclusions Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase-2-reentry. Quinidine, cilostazol and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities. PMID:24429494

  10. Cellular and ionic mechanisms underlying the effects of cilostazol, milrinone, and isoproterenol to suppress arrhythmogenesis in an experimental model of early repolarization syndrome.

    PubMed

    Patocskai, Bence; Barajas-Martinez, Hector; Hu, Dan; Gurabi, Zsolt; Koncz, István; Antzelevitch, Charles

    2016-06-01

    Early repolarization syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and ventricular fibrillation, leading to sudden cardiac death. The present study tests the hypothesis that the transient outward potassium current (Ito)-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Transmembrane action potentials (APs) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left ventricular (LV) wedge preparations, together with a transmural pseudo-electrocardiogram. The Ito agonist NS5806 (7-15 μM) and L-type calcium current (ICa) blocker verapamil (2-3 μM) were used to induce an early repolarization pattern and PVT. After stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase 2 reentry and PVT. Arrhythmic activity was suppressed in 7 of 8 preparations by cilostazol (10 μM), 6 of 7 by milrinone (2.5 μM), and 7 of 8 by isoproterenol (0.1-1 μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current during the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying the development of phase 2 reentry and ventricular tachycardia/ventricular fibrillation. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  11. Cellular and Ionic Mechanisms Underlying Effects of Cilostazol, Milrinone and Isoproterenol to Suppress Arrhythmogenesis in an Experimental Model of Early Repolarization Syndrome

    PubMed Central

    Patocskai, Bence; Barajas-Martinez, Hector; Hu, Dan; Gurabi, Zsolt; Koncz, István; Antzelevitch, Charles

    2016-01-01

    Background Early Repolarization Syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and fibrillation (VF), leading to sudden cardiac death. Objective The present study tests the hypothesis that the Ito-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Methods Transmembrane action potentials (AP) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left-ventricular (LV) wedge preparations, together with a transmural pseudo-ECG. The Ito-agonist NS5806 (7–15 μM) and ICa-blocker verapamil (2–3 uM) were used to induce an ER pattern and PVT. Results Following stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase-2-reentry (P2R) and PVT. Arrhythmic activity was suppressed in 7/8 preparations by cilostazol (10 μM), 6/7 by milrinone (2.5 μM) and 7/8 by isoproterenol (0.1–1μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. Conclusions Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current in the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying development of P2R and VT/VF. PMID:26820510

  12. Toxicology and cellular effect of manufactured nanomaterials

    DOEpatents

    Chen, Fanqing

    2014-07-22

    The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

  13. Gravitational Effects on Cellular Flame Structure

    NASA Technical Reports Server (NTRS)

    Dunsky, C. M.; Fernandez-Pello, A. C.

    1991-01-01

    An experimental investigation has been conducted of the effect of gravity on the structure of downwardly propagating, cellular premixed propane-oxygen-nitrogen flames anchored on a water-cooled porous-plug burner. The flame is subjected to microgravity conditions in the NASA Lewis 2.2-second drop tower, and flame characteristics are recorded on high-speed film. These are compared to flames at normal gravity conditions with the same equivalence ratio, dilution index, mixture flow rate, and ambient pressure. The results show that the cellular instability band, which is located in the rich mixture region, changes little under the absence of gravity. Lifted normal-gravity flames near the cellular/lifted limits, however, are observed to become cellular when gravity is reduced. Observations of a transient cell growth period following ignition point to heat loss as being an important mechanism in the overall flame stability, dominating the stabilizing effect of buoyancy for these downwardly-propagating burner-anchored flames. The pulsations that are observed in the plume and diffusion flame generated downstream of the premixed flame in the fuel rich cases disappear in microgravity, verifying that these fluctuations are gravity related.

  14. Thymus vulgaris essential oil and thymol against Alternaria alternata (Fr.) Keissler: effects on growth, viability, early infection and cellular mode of action.

    PubMed

    Perina, Fabiano J; Amaral, Douglas C; Fernandes, Rafael S; Labory, Claudia Rg; Teixeira, Glauco A; Alves, Eduardo

    2015-10-01

    In initial assays, Thymus vulgaris essential oil (TEO) has demonstrated activity against several plant-pathogenic fungi and has reduced the fungal diseases to levels comparable with commercial fungicides. Thus, the goal of this work was to identify the mode of action in fungi of TEO and its major compound thymol (TOH) at the cellular level using an ultrastructure approach. TEO from leaves and TOH had minimum inhibitory concentrations (MICs) of 500 and 250 µg mL(-1) respectively against A. alternata; under the same conditions, MIC for a commercial fungicide was 1250 µg mL(-1) . Ultrastructure analysis showed that TOH phenolic substance prevented fungal growth, reduced fungal viability and prevented the penetration in fruits by a cell wall/plasma membrane interference mode of action with organelles targeted for destruction in the cytoplasm. Such mode of action differs from protective and preventive-curative commercial fungicides used as pattern control. These findings suggest that TOH was responsible for the antifungal activity of TEO. Therefore, both the essential oil and its major substance have potential for use in the development of new phenolic structures and analogues to control Alternaria brown spot disease caused by Alternaria alternata. © 2014 Society of Chemical Industry.

  15. Nerolidol effects on mitochondrial and cellular energetics.

    PubMed

    Ferreira, Fernanda M; Palmeira, Carlos M; Oliveira, Maria M; Santos, Dario; Simões, Anabela M; Rocha, Sílvia M; Coimbra, Manuel A; Peixoto, Francisco

    2012-03-01

    In the present work, we evaluated the potential toxic effects of nerolidol, a sesquiterpenoid common in plants essential oils, both on mitochondrial and cellular energetics. Samples of enriched natural extracts of nerolidol (a racemic mixture of cis and trans isomers) were tested on rat liver mitochondria and a decrease in phosphorylative system was observed but not in the mitochondrial respiratory chain activity, which reflects a direct effect on F1-ATPase. Hence, respiratory control ratio was also decreased. Cellular ATP/ADP levels were significantly decreased in a concentration-dependent manner, possibly due to the direct effect of nerolidol on F(0)F(1)-ATPsynthase. Nerolidol stimulates respiratory activity probably due to an unspecific effect, since it does not show any protonophoric effect. Furthermore, we observed that mitochondrial permeability transition was delayed in the presence of nerolidol, possibly due to its antioxidant activity and because this compound decreases mitochondrial transmembrane electric potential. Our results also show that, in human hepatocellular liver carcinoma cell line (HepG2), nerolidol both induces cell death and arrests cell growth, probably related with the observed lower bioenergetic efficiency. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

    EPA Science Inventory

    CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...

  17. Cellular autofluorescence imaging for early diagnosis of cancers

    NASA Astrophysics Data System (ADS)

    Steenkeste, Karine; Deniset, Ariane; Lecart, Sandrine; Leveque-Fort, Sandrine; Fontaine-Aupart, Marie-Pierre; Ferlicot, Sophie; Eschwege, Pascal

    2005-08-01

    Urinary cytology is employed in diagnostic guidelines of bladder cancer in anatomo-pathological laboratories mostly for its ability to diagnose non detectable cancers using cystoscopy, but also because it is a non-invasive and non-constraining technique for a regular follow-up of the more exposed populations. The impossibility to detect such cancers is mainly due to their localization either in the bladder or in the upper urinary tract and the prostate. However, urinary cytology lacks sensitivity, especially for the detection of low grade low stage tumors due to inherent limitation of morphological criteria to distinguish low grade tumor cells from normal urothelial cells. For this purpose, we developed, in addition to urinary cytology, an original screening of these cytological slides by using spectrally-resolved and time-resolved fluorescence as a contrast factor, without changing any parameters in the cytological slide preparation. This method takes advantage of a femtosecond Ti:sapphire laser, continuously tunable in the spectral range 700-950 nm allowing the observation of most endogenous cellular chromophores by biphotonic excitation. A commercial confocal microscope was also used in the measurements allowing an excitation of the samples between 458 nm and 633 nm. We observed that the fluorescence emission is differentially distributed in normal and pathological urothelial cells. Spectral- and time-resolved measurements attested this difference over about one hundred cases which have been tested to confirm the high accuracy of this non-invasive technique.

  18. Telomere length and early severe social deprivation: linking early adversity and cellular aging

    PubMed Central

    Drury, SS; Theall, K; Gleason, MM; Smyke, AT; De Vivo, I; Wong, JYY; Fox, NA; Zeanah, CH; Nelson, CA

    2012-01-01

    Accelerated telomere length attrition has been associated with psychological stress and early adversity in adults; however, no studies have examined whether telomere length in childhood is associated with early experiences. The Bucharest Early Intervention Project is a unique randomized controlled trial of foster care placement compared with continued care in institutions. As a result of the study design, participants were exposed to a quantified range of time in institutional care, and represented an ideal population in which to examine the association between a specific early adversity, institutional care and telomere length. We examined the association between average relative telomere length, telomere repeat copy number to single gene copy number (T/S) ratio and exposure to institutional care quantified as the percent of time at baseline (mean age 22 months) and at 54 months of age that each child lived in the institution. A significant negative correlation between T/S ratio and percentage of time was observed. Children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified this main effect. The percentage of time in institutional care at baseline significantly predicted telomere length in females, whereas the percentage of institutional care at 54 months was strongly predictive of telomere length in males. This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children, and contributes to the growing literature linking telomere length and early adversity. PMID:21577215

  19. Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

    PubMed Central

    Huang, Li-Tung

    2014-01-01

    Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

  20. Massive cellular disruption occurs during early imbibition of Cuphea seeds containing crystallized triacylglycerols.

    PubMed

    Volk, Gayle M; Crane, Jennifer; Caspersen, Ann M; Hill, Lisa M; Gardner, Candice; Walters, Christina

    2006-11-01

    The transition from anhydrobiotic to hydrated state occurs during early imbibition of seeds and is lethal if lipid reserves in seeds are crystalline. Low temperatures crystallize lipids during seed storage. We examine the nature of cellular damage observed in seeds of Cuphea wrightii and C. lanceolata that differ in triacylglycerol composition and phase behavior. Intracellular structure, observed using transmission electron microscopy, is profoundly and irreversibly perturbed if seeds with crystalline triacylglycerols are imbibed briefly. A brief heat treatment that melts triacylglycerols before imbibition prevents the loss of cell integrity; however, residual effects of cold treatments in C. wrightii cells are reflected by the apparent coalescence of protein and oil bodies. The timing and temperature dependence of cellular changes suggest that damage arises via a physical mechanism, perhaps as a result of shifts in hydrophobic and hydrophilic interactions when triacylglycerols undergo phase changes. Stabilizers of oil body structure such as oleosins that rely on a balance of physical forces may become ineffective when triacylglycerols crystallize. Recent observations linking poor oil body stability and poor seed storage behavior are potentially explained by the phase behavior of the storage lipids. These findings directly impact the feasibility of preserving genetic resources from some tropical and subtropical species.

  1. Modeling the mechanics of cancer: effect of changes in cellular and extra-cellular mechanical properties.

    PubMed

    Katira, Parag; Bonnecaze, Roger T; Zaman, Muhammad H

    2013-01-01

    Malignant transformation, though primarily driven by genetic mutations in cells, is also accompanied by specific changes in cellular and extra-cellular mechanical properties such as stiffness and adhesivity. As the transformed cells grow into tumors, they interact with their surroundings via physical contacts and the application of forces. These forces can lead to changes in the mechanical regulation of cell fate based on the mechanical properties of the cells and their surrounding environment. A comprehensive understanding of cancer progression requires the study of how specific changes in mechanical properties influences collective cell behavior during tumor growth and metastasis. Here we review some key results from computational models describing the effect of changes in cellular and extra-cellular mechanical properties and identify mechanistic pathways for cancer progression that can be targeted for the prediction, treatment, and prevention of cancer.

  2. The roles of cellular and molecular components of a hematoma at early stage of bone healing.

    PubMed

    Shiu, Hoi Ting; Leung, Ping Chung; Ko, Chun Hay

    2018-04-01

    Bone healing is a complex repair process that commences with the formation of a blood clot at the injured bone, termed hematoma. It has evidenced that a lack of a stable hematoma causes delayed bone healing or non-union. The hematoma at the injured bone constitutes the early healing microenvironment. It appears to dictate healing pathways that ends in a regenerative bone. However, the hematoma is often clinically removed from the damaged site. Conversely, blood-derived products have been used in bone tissue engineering for treating critical sized defects, including fibrin gels and platelet-rich plasma. A second generation of platelet concentrate that is based on leukocyte and fibrin content has also been developed and introduced in market. Conflicting effect of these products in bone repair are reported. We propose that the bone healing response becomes dysregulated if the blood response and subsequent formation and properties of a hematoma are altered. This review focuses on the central structural, cellular, and molecular components of a fracture hematoma, with a major emphasis on their roles in regulating bone healing mechanism, and their interactions with mesenchymal stem cells. New angles towards a better understanding of these factors and relevant mechanisms involved at the beginning of bone healing may help to clarify limited or adverse effects of blood-derived products on bone repair. We emphasize that the recreation of an early hematoma niche with critical compositions might emerge as a viable therapeutic strategy for enhanced skeletal tissue engineering. Copyright © 2017 John Wiley & Sons, Ltd.

  3. The cellular immunity and oxidative stress markers in early pregnancy loss.

    PubMed

    Daglar, Korkut; Biberoglu, Ebru; Kirbas, Ayse; Dirican, Aylin Onder; Genc, Metin; Avci, Aslihan; Biberoglu, Kutay

    2016-01-01

    We investigated whether changes in cellular immunity and oxidative stress in pregnancy have any association with spontaneous miscarriage. Circulating adenosine deaminase (ADA) activity as a marker of cellular immunity and malondialdehyde (MDA) and catalase (CAT), glutathione peroxidase (GPx) as markers of T lymphocyte activation and parameters of oxidative stress and antioxidant defense were compared between 40 women with early pregnancy loss and another 40 women with ungoing healthy pregnancy. Women with miscarriage had higher serum ADA and GPx levels when compared with women with normal pregnancy (p = 0.034 and p < 0.001, respectively). Although serum MDA level was slightly higher in women with miscarriage, the difference was not significant (p = 0.083). CAT levels were alike in both groups. We have demonstrated an increased cellular immunity and perhaps a compensated oxidative stress related to increased antioxidant activation in women with early spontaneous pregnancy loss.

  4. The Effect of Gravity Fields on Cellular Gene Expression

    NASA Technical Reports Server (NTRS)

    Hughes-Fulford, Millie

    1999-01-01

    Early theoretical analysis predicted that microgravity effects on the isolated cell would be minuscule at the subcellular level; however, these speculations have not proven true in the real world. Astronauts experience a significant bone and muscle loss in as little as 2 weeks of spaceflight and changes are seen at the cellular level soon after exposure to microgravity. Changes in biological systems may be primarily due to the lack of gravity and the resulting loss of mechanical stress on tissues and cells. Recent ground and flight studies examining the effects of gravity or mechanical stress on cells demonstrate marked changes in gene expression when relatively small changes in mechanical forces or gravity fields were made. Several immediate early genes (IEG) like c-fos and c-myc are induced by mechanical stimulation within minutes. In contrast, several investigators report that the absence of mechanical forces during space flight result in decreased sera response element (SRE) activity and attenuation of expression of IEGs such as c-fos, c-jun and cox-2 mRNAs. Clearly, these early changes in gene expression may have long term consequences on mechanically sensitive cells. In our early studies on STS-56, we reported four major changes in the osteoblast; 1) prostaglandin synthesis in flight, 2) changes in cellular morphology, 3) altered actin cytoskeleton and 4) reduced osteoblast growth after four days exposure to microgravity. Initially, it was believed that changes in fibronectin (FN) RNA, FN protein synthesis or subsequent FN matrix formation might account for the changes in cytoskeleton and/ or reduction of growth. However our recent studies on Biorack (STS-76, STS-81 and STS-84), using ground and in-flight 1-G controls, demonstrated that fibronectin synthesis and matrix formation were normal in microgravity. In addition, in our most recent Biorack paper, our laboratory has documented that relative protein synthesis and mRNA synthesis are not changed after 24

  5. Two distinct cellular proteins interact with the EIa-responsive element of an adenovirus early promoter.

    PubMed Central

    Jansen-Durr, P; Wintzerith, M; Reimund, B; Hauss, C; Kédinger, C

    1990-01-01

    EIa-dependent transactivation of the adenovirus EIIa early (EIIaE) promoter is correlated with the activation of the cellular transcription factor E2F. In this study we identified a cellular protein, C alpha, that is distinct from E2F and that binds two sites in the EIIaE promoter, one of which overlaps with the proximal E2F binding site of the EIIaE promoter. The possible involvement of C alpha in the EIa responsiveness of this promoter is discussed. Images PMID:2139142

  6. Cellular Effects of Perfluorinated Fatty Acids (PFDA).

    DTIC Science & Technology

    This is a proposal to investigate the effects of perfluorinated decanoic acid ( PFDA ) on the cell surface of liver cells and tissue. The major method...summarized as follows: (a) differentiated liver tissue culture cells in vitro do have the membrane fluidity affected by PFDA whereas undifferentiated, non...d) the effect on mobility occurs within 24 hours of exposure without further increase with time of exposure; (e) scanning EM demonstrates no gross structural abnormality of the surface as a result of the non-toxic levels of PFDA .

  7. Cellular Effects of Perfluorinated Fatty Acids.

    DTIC Science & Technology

    1985-01-01

    perfluoro -n-de canoic acid ( PFDA ), fluoresce e -- I j ~recovery after photobleaching (FRAPB), cell culture ~ . 19. ABSTRACT (Continue an reverse if...necessmzejj dctiy by block number) --Tecompoubd perfluor i--ecan’oic’ acid ( PFDA ) was exposed to three tissue culturer cell lines, PTK2 (kidney),/BRL (buffalo...all cell systems. In particular, previous in vivo and in vitro studies on the similarities of the toxic effects of perfluoro -n-decanoic acid ( PFDA ) and

  8. The effects of storage and sterilization on de-cellularized and re-cellularized whole lung.

    PubMed

    Bonenfant, Nicholas R; Sokocevic, Dino; Wagner, Darcy E; Borg, Zachary D; Lathrop, Melissa J; Lam, Ying Wai; Deng, Bin; Desarno, Michael J; Ashikaga, Taka; Loi, Roberto; Weiss, Daniel J

    2013-04-01

    Despite growing interest on the potential use of de-cellularized whole lungs as 3-dimensional scaffolds for ex vivo lung tissue generation, optimal processing including sterilization and storage conditions, are not well defined. Further, it is unclear whether lungs need to be obtained immediately or may be usable even if harvested several days post-mortem, a situation mimicking potential procurement of human lungs from autopsy. We therefore assessed effects of delayed necropsy, prolonged storage (3 and 6 months), and of two commonly utilized sterilization approaches: irradiation or final rinse with peracetic acid, on architecture and extracellular matrix (ECM) protein characteristics of de-cellularized mouse lungs. These different approaches resulted in significant differences in both histologic appearance and in retention of ECM and intracellular proteins as assessed by immunohistochemistry and mass spectrometry. Despite these differences, binding and proliferation of bone marrow-derived mesenchymal stromal cells (MSCs) over a one month period following intratracheal inoculation was similar between experimental conditions. In contrast, significant differences occurred with C10 mouse lung epithelial cells between the different conditions. Therefore, delayed necropsy, duration of scaffold storage, sterilization approach, and cell type used for re-cellularization may significantly impact the usefulness of this biological scaffold-based model of ex vivo lung tissue regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Reviewing the current evidence supporting early B-cells as the cellular origin of Merkel cell carcinoma.

    PubMed

    Sauer, C M; Haugg, A M; Chteinberg, E; Rennspiess, D; Winnepenninckx, V; Speel, E-J; Becker, J C; Kurz, A K; Zur Hausen, A

    2017-08-01

    Merkel cell carcinoma (MCC) is a highly malignant skin cancer characterized by early metastases and poor survival. Although MCC is a rare malignancy, its incidence is rapidly increasing in the U.S. and Europe. The discovery of the Merkel cell polyomavirus (MCPyV) has enormously impacted our understanding of its etiopathogenesis and biology. MCCs are characterized by trilinear differentiation, comprising the expression of neuroendocrine, epithelial and B-lymphoid lineage markers. To date, it is generally accepted that the initial assumption of MCC originating from Merkel cells (MCs) is unlikely. This is owed to their post-mitotic character, absence of MCPyV in MCs and discrepant protein expression pattern in comparison to MCC. Evidence from mouse models suggests that epidermal/dermal stem cells might be of cellular origin in MCC. The recently formulated hypothesis of MCC originating from early B-cells is based on morphology, the consistent expression of early B-cell lineage markers and the finding of clonal immunoglobulin chain rearrangement in MCC cells. In this review we elaborate on the cellular ancestry of MCC, the identification of which could pave the way for novel and more effective therapeutic regimens. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. The Effectiveness of Early Intervention.

    ERIC Educational Resources Information Center

    Guralnick, Michael J., Ed.

    This book reviews research on the effectiveness of early intervention for children with disabilities or who are at risk. Program factors for children at risk and with disabilities, the effects of early intervention on different types of disabilities, and the outcomes of early intervention are explored. Chapters include: "Second-Generation Research…

  11. The evolution of early cellular systems viewed through the lens of biological interactions.

    PubMed

    Poole, Anthony M; Lundin, Daniel; Rytkönen, Kalle T

    2015-01-01

    The minimal cell concept represents a pragmatic approach to the question of how few genes are required to run a cell. This is a helpful way to build a parts-list, and has been more successful than attempts to deduce a minimal gene set for life by inferring the gene repertoire of the last universal common ancestor, as few genes trace back to this hypothetical ancestral state. However, the study of minimal cellular systems is the study of biological outliers where, by practical necessity, coevolutionary interactions are minimized or ignored. In this paper, we consider the biological context from which minimal genomes have been removed. For instance, some of the most reduced genomes are from endosymbionts and are the result of coevolutionary interactions with a host; few such organisms are "free-living." As few, if any, biological systems exist in complete isolation, we expect that, as with modern life, early biological systems were part of an ecosystem, replete with organismal interactions. We favor refocusing discussions of the evolution of cellular systems on processes rather than gene counts. We therefore draw a distinction between a pragmatic minimal cell (an interesting engineering problem), a distributed genome (a system resulting from an evolutionary transition involving more than one cell) and the looser coevolutionary interactions that are ubiquitous in ecosystems. Finally, we consider the distributed genome and coevolutionary interactions between genomic entities in the context of early evolution.

  12. Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

    PubMed

    Saraf, Rabya; Huang, Thomas; Mahmood, Feroze; Owais, Khurram; Bardia, Amit; Khabbaz, Kamal R; Liu, David; Senthilnathan, Venkatachalam; Lassaletta, Antonio D; Sellke, Frank; Matyal, Robina

    2016-01-01

    Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome. Yorkshire swine (n = 8 per group) were fed a normal diet (ND) or a high-cholesterol (HCD) for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD). There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively) in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002) and Bcl-xL (p = 0.05 and p = 0.01) in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p = 0.01), pSmad1/5 (p = 0.03) and MMP-9 (p = 0.005) were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively). Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and-dp/dt (p = 0.05 and p = 0.007 respectively) in the HCD group. Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.

  13. Coordination of cellular differentiation, polarity, mitosis and meiosis - New findings from early vertebrate oogenesis.

    PubMed

    Elkouby, Yaniv M; Mullins, Mary C

    2017-10-15

    A mechanistic dissection of early oocyte differentiation in vertebrates is key to advancing our knowledge of germline development, reproductive biology, the regulation of meiosis, and all of their associated disorders. Recent advances in the field include breakthroughs in the identification of germline stem cells in Medaka, in the cellular architecture of the germline cyst in mice, in a mechanistic dissection of chromosomal pairing and bouquet formation in meiosis in mice, in tracing oocyte symmetry breaking to the chromosomal bouquet of meiosis in zebrafish, and in the biology of the Balbiani body, a universal oocyte granule. Many of the major events in early oogenesis are universally conserved, and some are co-opted for species-specific needs. The chromosomal events of meiosis are of tremendous consequence to gamete formation and have been extensively studied. New light is now being shed on other aspects of early oocyte differentiation, which were traditionally considered outside the scope of meiosis, and their coordination with meiotic events. The emerging theme is of meiosis as a common groundwork for coordinating multifaceted processes of oocyte differentiation. In an accompanying manuscript we describe methods that allowed for investigations in the zebrafish ovary to contribute to these breakthroughs. Here, we review these advances mostly from the zebrafish and mouse. We discuss oogenesis concepts across established model organisms, and construct an inclusive paradigm for early oocyte differentiation in vertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Early warning of illegal development for protected areas by integrating cellular automata with neural networks.

    PubMed

    Li, Xia; Lao, Chunhua; Liu, Yilun; Liu, Xiaoping; Chen, Yimin; Li, Shaoying; Ai, Bing; He, Zijian

    2013-11-30

    Ecological security has become a major issue under fast urbanization in China. As the first two cities in this country, Shenzhen and Dongguan issued the ordinance of Eco-designated Line of Control (ELC) to "wire" ecologically important areas for strict protection in 2005 and 2009 respectively. Early warning systems (EWS) are a useful tool for assisting the implementation ELC. In this study, a multi-model approach is proposed for the early warning of illegal development by integrating cellular automata (CA) and artificial neural networks (ANN). The objective is to prevent the ecological risks or catastrophe caused by such development at an early stage. The integrated model is calibrated by using the empirical information from both remote sensing and handheld GPS (global positioning systems). The MAR indicator which is the ratio of missing alarms to all the warnings is proposed for better assessment of the model performance. It is found that the fast urban development has caused significant threats to natural-area protection in the study area. The integration of CA, ANN and GPS provides a powerful tool for describing and predicting illegal development which is in highly non-linear and fragmented forms. The comparison shows that this multi-model approach has much better performances than the single-model approach for the early warning. Compared with the single models of CA and ANN, this integrated multi-model can improve the value of MAR by 65.48% and 5.17% respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Are cellular phone blocking applications effective for novice teen drivers?

    PubMed

    Creaser, Janet I; Edwards, Christopher J; Morris, Nichole L; Donath, Max

    2015-09-01

    Distracted driving is a significant concern for novice teen drivers. Although cellular phone bans are applied in many jurisdictions to restrict cellular phone use, teen drivers often report making calls and texts while driving. The Minnesota Teen Driver Study incorporated cellular phone blocking functions via a software application for 182 novice teen drivers in two treatment conditions. The first condition included 92 teens who ran a driver support application on a smartphone that also blocked phone usage. The second condition included 90 teens who ran the same application with phone blocking but which also reported back to parents about monitored risky behaviors (e.g., speeding). A third control group consisting of 92 novice teen drivers had the application and phone-based software installed on the phones to record cellular phone (but not block it) use while driving. The two treatment groups made significantly fewer calls and texts per mile driven compared to the control group. The control group data also demonstrated a higher propensity to text while driving rather than making calls. Software that blocks cellular phone use (except 911) while driving can be effective at mitigating calling and texting for novice teen drivers. However, subjective data indicates that some teens were motivated to find ways around the software, as well as to use another teen's phone while driving when they were unable to use theirs. Cellular phone bans for calling and texting are the first step to changing behaviors associated with texting and driving, particularly among novice teen drivers. Blocking software has the additional potential to reduce impulsive calling and texting while driving among novice teen drivers who might logically know the risks, but for whom it is difficult to ignore calling or texting while driving. Copyright © 2015 Elsevier Ltd and National Safety Council. All rights reserved.

  16. Magnetic Resonance Imaging to Detect Early Molecular and Cellular Changes in Alzheimer's Disease.

    PubMed

    Knight, Michael J; McCann, Bryony; Kauppinen, Risto A; Coulthard, Elizabeth J

    2016-01-01

    Recent pharmaceutical trials have demonstrated that slowing or reversing pathology in Alzheimer's disease is likely to be possible only in the earliest stages of disease, perhaps even before significant symptoms develop. Pathology in Alzheimer's disease accumulates for well over a decade before symptoms are detected giving a large potential window of opportunity for intervention. It is therefore important that imaging techniques detect subtle changes in brain tissue before significant macroscopic brain atrophy. Current diagnostic techniques often do not permit early diagnosis or are too expensive for routine clinical use. Magnetic Resonance Imaging (MRI) is the most versatile, affordable, and powerful imaging modality currently available, being able to deliver detailed analyses of anatomy, tissue volumes, and tissue state. In this mini-review, we consider how MRI might detect patients at risk of future dementia in the early stages of pathological change when symptoms are mild. We consider the contributions made by the various modalities of MRI (structural, diffusion, perfusion, relaxometry) in identifying not just atrophy (a late-stage AD symptom) but more subtle changes reflective of early dementia pathology. The sensitivity of MRI not just to gross anatomy but to the underlying "health" at the cellular (and even molecular) scales, makes it very well suited to this task.

  17. Early detection of disease program: Evaluation of the cellular immune response

    NASA Technical Reports Server (NTRS)

    Criswell, B. S.; Knight, V.; Martin, R. R.; Kasel, J. A.

    1974-01-01

    The early cellular responses of specific components of the leukocyte and epithelial cell populations to foreign challenges of both an infectious and noninfectious character were evaluated. Procedures for screening potential flight crews were developed, documented, and tested on a control population. Methods for preparing suitable populations of lymphocytes, polymorphonuclear leukocytes, macrophages, and epithelial cells were first established and evaluated. Epithelial cells from viral infected individuals were screened with a number of anti-viral antisera. This procedure showed the earliest indication of disease as well as providing a specific diagnosis to the physicians. Both macrophages and polymorphonuclear leukocytes were studied from normal individuals, smokers, and patients with viral infections. Newer techniques enabling better definition of lymphocyte subpopulations were then developed, namely the E and EAC rosette procedures for recognition of T (thymus-derived) and B (bone-marrow-derived) lymphocyte subpopulations. Lymphocyte and lymphocyte subpopulation response to multiple mitogens have been evaluated.

  18. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

    DOE PAGES

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz; ...

    2017-03-22

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  19. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

    SciTech Connect

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  20. Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level.

    PubMed

    Humphreys, Kathryn L; Esteves, Kyle; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A; Drury, Stacy S

    2016-12-30

    Studies examining the association between early adversity and longitudinal changes in telomere length within the same individual are rare, yet are likely to provide novel insight into the subsequent lasting effects of negative early experiences. We sought to examine the association between institutional care history and telomere shortening longitudinally across middle childhood and into adolescence. Buccal DNA was collected 2-4 times, between the ages of 6 and 15 years, in 79 children enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal study exploring the impact of early institutional rearing on child health and development. Children with a history of early institutional care (n=50) demonstrated significantly greater telomere shortening across middle childhood and adolescence compared to never institutionalized children (n=29). Among children with a history of institutional care, randomization to high quality foster care was not associated with differential telomere attrition across development. Cross-sectional analysis of children randomized to the care as usual group indicated shorter telomere length was associated with greater percent of the child's life spent in institutional care up to age 8. These results suggest that early adverse care from severe psychosocial deprivation may be embedded at the molecular genetic level through accelerated telomere shortening. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level

    PubMed Central

    Humphreys, Kathryn L.; Esteves, Kyle; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A.; Drury, Stacy S.

    2016-01-01

    Studies examining the association between early adversity and longitudinal changes in telomere length within the same individual are rare, yet are likely to provide novel insight into the subsequent lasting effects of negative early experiences. We sought to examine the association between institutional care history and telomere shortening longitudinally across middle childhood and into adolescence. Buccal DNA was collected 2 to 4 times, between the ages of 6 and 15 years, in 79 children enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal study exploring the impact of early institutional rearing on child health and development. Children with a history of early institutional care (n=50) demonstrated significantly greater telomere shortening across middle childhood and adolescence compared to never institutionalized children (n=29). Among children with a history of institutional care, randomization to high quality foster care was not associated with differential telomere attrition across development. Cross-sectional analysis of children randomized to the care as usual group indicated shorter telomere length was associated with greater percent of the child’s life spent in institutional care up to age 8. These results suggest that early adverse care from severe psychosocial deprivation may be embedded at the molecular genetic level through accelerated telomere shortening. PMID:27677058

  2. Quantification of nanoscale density fluctuations by electron microscopy: probing cellular alterations in early carcinogenesis

    NASA Astrophysics Data System (ADS)

    Pradhan, Prabhakar; Damania, Dhwanil; Joshi, Hrushikesh M.; Turzhitsky, Vladimir; Subramanian, Hariharan; Roy, Hemant K.; Taflove, Allen; Dravid, Vinayak P.; Backman, Vadim

    2011-04-01

    Most cancers are curable if they are diagnosed and treated at an early stage. Recent studies suggest that nanoarchitectural changes occur within cells during early carcinogenesis and that such changes precede microscopically evident tissue alterations. It follows that the ability to comprehensively interrogate cell nanoarchitecture (e.g., macromolecular complexes, DNA, RNA, proteins and lipid membranes) could be critical to the diagnosis of early carcinogenesis. We present a study of the nanoscale mass-density fluctuations of biological tissues by quantifying their degree of disorder at the nanoscale. Transmission electron microscopy images of human tissues are used to construct corresponding effective disordered optical lattices. The properties of nanoscale disorder are then studied by statistical analysis of the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices at the nanoscale. Our results show an increase in the disorder of human colonic epithelial cells in subjects harboring early stages of colon neoplasia. Furthermore, our findings strongly suggest that increased nanoscale disorder correlates with the degree of tumorigenicity. Therefore, the IPR technique provides a practicable tool for the detection of nanoarchitectural alterations in the earliest stages of carcinogenesis. Potential applications of the technique for early cancer screening and detection are also discussed. Originally submitted for the special focus issue on physical oncology.

  3. Jahn-Teller effect in molecular electronics: quantum cellular automata

    NASA Astrophysics Data System (ADS)

    Tsukerblat, B.; Palii, A.; Clemente-Juan, J. M.; Coronado, E.

    2017-05-01

    The article summarizes the main results of application of the theory of the Jahn-Teller (JT) and pseudo JT effects to the description of molecular quantum dot cellular automata (QCA), a new paradigm of quantum computing. The following issues are discussed: 1) QCA as a new paradigm of quantum computing, principles and advantages; 2) molecular implementation of QCA; 3) role of the JT effect in charge trapping, encoding of binary information in the quantum cell and non-linear cell-cell response; 4) spin-switching in molecular QCA based on mixed-valence cell; 5) intervalence optical absorption in tetrameric molecular mixed-valence cell through the symmetry assisted approach to the multimode/multilevel JT and pseudo JT problems.

  4. Early Alterations of Brain Cellular Energy Homeostasis in Huntington Disease Models*

    PubMed Central

    Mochel, Fanny; Durant, Brandon; Meng, Xingli; O'Callaghan, James; Yu, Hua; Brouillet, Emmanuel; Wheeler, Vanessa C.; Humbert, Sandrine; Schiffmann, Raphael; Durr, Alexandra

    2012-01-01

    Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in HdhQ111/+ mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool. PMID:22123819

  5. Regulation of the cellular and physiological effects of glutamine.

    PubMed

    Chwals, Walter J

    2004-10-01

    Glutamine is the most abundant amino acid in humans and possesses many functions in the body. It is the major transporter of amino-nitrogen between cells and an important fuel source for rapidly dividing cells such as cells of the immune and gastrointestinal systems. It is important in the synthesis of nucleic acids, glutathione, citrulline, arginine, gamma aminobutyric acid, and glucose. It is important for growth, gastrointestinal integrity, acid-base homeostasis, and optimal immune function. The regulation of glutamine levels in cells via glutaminase and glutamine synthetase is discussed. The cellular and physiologic effects of glutamine upon the central nervous system, gastrointestinal function, during metabolic support, and following tissue injury and critical illness is also discussed.

  6. Cellular and physiological effects of medium-chain triglycerides.

    PubMed

    Wanten, Geert J; Naber, Anton H

    2004-10-01

    From a nutritional standpoint, saturated triglycerides with a medium (6 to 12) carbon chain length (MCT) have traditionally been regarded as biologically inert substances, merely serving as a source of fuel calories that is relatively easily accessible for metabolic breakdown compared with long chain triglycerides (LCT). This quality of MCT has been shown to offer both benefits and risks depending on the clinical situation, with potential positive effects on protein metabolism in some studies on one side, and an increased risk for ketogenesis and metabolic acidosis on the other. At another level, studies regarding lipid effects of MCT on the immune system, as with LCT, so far have yielded equivocal results, although there is a recent experimental evidence to suggest that MCT possess immune modulating properties and should in fact be regarded as bioactive mediators. Most of this information comes from studies where effects of MCT have been compared with those of LCT in lipid emulsions, as part of parenteral (intravenous) nutrition formulations. Unfortunately, the relevance of these observations for clinical practice remains largely unclear because adequately powered trials that clearly point out the position of MCT in relation to structurally different lipids have not been performed. In the present paper we review the experimental and clinical evidence for cellular and physiological effects of nutritional MCT. In addition, studies describing possible mechanisms behind the observed effects of MCT will be discussed.

  7. Cellular and molecular effects of yeast probiotics on cancer.

    PubMed

    Saber, Amir; Alipour, Beitollah; Faghfoori, Zeinab; Yari Khosroushahi, Ahmad

    2017-02-01

    The cancer is one of the main causes of human deaths worldwide. The exact mechanisms of initiation and progression of malignancies are not clear yet, but there is a common agreement about the role of colonic microbiota in the etiology of different cancers. Probiotics have been examined for their anti-cancer effects, and different mechanisms have been suggested about their antitumor functions. Nonpathogenic yeasts, as members of probiotics family, can be effective on gut microbiota dysbiosis. Generally safe yeasts have shown so many beneficial effects on human health. Probiotic yeasts influence physiology, metabolism, and immune homeostasis in the colon and contribute to cancer treatment due to possessing anti-inflammatory, anti-proliferative and anti-cancer properties. This study reviews some of the health-beneficial effects of probiotic yeasts and their biological substances like folic acid and β-glucan on cancer and focuses on the possible cellular and molecular mechanisms of probiotic yeasts such as influencing pathogenic bacteria, inactivation of carcinogenic compounds, especially those derived from food, improvement of intestinal barrier function, modulation of immune responses, antitoxic function, apoptosis, and anti-proliferative effects.

  8. Early vertebrate origin and diversification of small transmembrane regulators of cellular ion transport.

    PubMed

    Pirkmajer, Sergej; Kirchner, Henriette; Lundell, Leonidas S; Zelenin, Pavel V; Zierath, Juleen R; Makarova, Kira S; Wolf, Yuri I; Chibalin, Alexander V

    2017-07-15

    Small transmembrane proteins such as FXYDs, which interact with Na + ,K + -ATPase, and the micropeptides that interact with sarco/endoplasmic reticulum Ca 2+ -ATPase play fundamental roles in regulation of ion transport in vertebrates. Uncertain evolutionary origins and phylogenetic relationships among these regulators of ion transport have led to inconsistencies in their classification across vertebrate species, thus hampering comparative studies of their functions. We discovered the first FXYD homologue in sea lamprey, a basal jawless vertebrate, which suggests small transmembrane regulators of ion transport emerged early in the vertebrate lineage. We also identified 13 gene subfamilies of FXYDs and propose a revised, phylogeny-based FXYD classification that is consistent across vertebrate species. These findings provide an improved framework for investigating physiological and pathophysiological functions of small transmembrane regulators of ion transport. Small transmembrane proteins are important for regulation of cellular ion transport. The most prominent among these are members of the FXYD family (FXYD1-12), which regulate Na + ,K + -ATPase, and phospholamban, sarcolipin, myoregulin and DWORF, which regulate the sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA). FXYDs and regulators of SERCA are present in fishes, as well as terrestrial vertebrates; however, their evolutionary origins and phylogenetic relationships are obscure, thus hampering comparative physiological studies. Here we discovered that sea lamprey (Petromyzon marinus), a representative of extant jawless vertebrates (Cyclostomata), expresses an FXYD homologue, which strongly suggests that FXYDs predate the emergence of fishes and other jawed vertebrates (Gnathostomata). Using a combination of sequence-based phylogenetic analysis and conservation of local chromosome context, we determined that FXYDs markedly diversified in the lineages leading to cartilaginous fishes (Chondrichthyes) and bony

  9. Direct and indirect cellular effects of aspartame on the brain.

    PubMed

    Humphries, P; Pretorius, E; Naudé, H

    2008-04-01

    The use of the artificial sweetener, aspartame, has long been contemplated and studied by various researchers, and people are concerned about its negative effects. Aspartame is composed of phenylalanine (50%), aspartic acid (40%) and methanol (10%). Phenylalanine plays an important role in neurotransmitter regulation, whereas aspartic acid is also thought to play a role as an excitatory neurotransmitter in the central nervous system. Glutamate, asparagines and glutamine are formed from their precursor, aspartic acid. Methanol, which forms 10% of the broken down product, is converted in the body to formate, which can either be excreted or can give rise to formaldehyde, diketopiperazine (a carcinogen) and a number of other highly toxic derivatives. Previously, it has been reported that consumption of aspartame could cause neurological and behavioural disturbances in sensitive individuals. Headaches, insomnia and seizures are also some of the neurological effects that have been encountered, and these may be accredited to changes in regional brain concentrations of catecholamines, which include norepinephrine, epinephrine and dopamine. The aim of this study was to discuss the direct and indirect cellular effects of aspartame on the brain, and we propose that excessive aspartame ingestion might be involved in the pathogenesis of certain mental disorders (DSM-IV-TR 2000) and also in compromised learning and emotional functioning.

  10. Human Papillomavirus Types 16 and 18 Early-expressed Proteins Differentially Modulate the Cellular Redox State and DNA Damage

    PubMed Central

    Cruz-Gregorio, Alfredo; Manzo-Merino, Joaquín; Gonzaléz-García, María Cecilia; Pedraza-Chaverri, José; Medina-Campos, Omar Noel; Valverde, Mahara; Rojas, Emilio; Rodríguez-Sastre, María Alexandra; García-Cuellar, Claudia María; Lizano, Marcela

    2018-01-01

    Oxidative stress has been proposed as a risk factor for cervical cancer development. However, few studies have evaluated the redox state associated with human papillomavirus (HPV) infection. The aim of this work was to determine the role of the early expressed viral proteins E1, E2, E6 and E7 from HPV types 16 and 18 in the modulation of the redox state in an integral form. Therefore, generation of reactive oxygen species (ROS), concentration of reduced glutathione (GSH), levels and activity of the antioxidant enzymes catalase and superoxide dismutase (SOD) and deoxyribonucleic acid (DNA) damage, were analysed in epithelial cells ectopically expressing the viral proteins. Our research shows that E6 oncoproteins decreased GSH and catalase protein levels, as well as its enzymatic activity, which was associated with an increase in ROS production and DNA damage. In contrast, E7 oncoproteins increased GSH, as well as catalase protein levels and its activity, which correlated with a decrease in ROS without affecting DNA integrity. The co-expression of both E6 and E7 oncoproteins neutralized the effects that were independently observed for each of the viral proteins. Additionally, the combined expression of E1 and E2 proteins increased ROS levels with the subsequent increase in the marker for DNA damage phospho-histone 2AX (γH2AX). A decrease in GSH, as well as SOD2 levels and activity were also detected in the presence of E1 and E2, even though catalase activity increased. This study demonstrates that HPV early expressed proteins differentially modulate cellular redox state and DNA damage. PMID:29483822

  11. Effect of high electromagnetic fields on cellular growth

    NASA Astrophysics Data System (ADS)

    Albalawi, Abdullah; Mustafa, Mohammed; Masood, Samina

    It is already known that high-intensity electromagnetic field affect the human lung growth and forces the T-cells to decrease by 20-30 percent. The electromagnetic field had a severe impact on human T-cells in contrast to lung cells. Due to the high-intensity electromagnetic field, the growth of T-cells becomes low and release of Ca+2 increases up to 3.5 times more than the lung cells. The high-intensity electromagnetic radiations do not directly produce cancer cells but had a severe impact on the growth of T-cells. It can also be said that electromagnetic field acts a role in the cancer initiation. It creates disordered in the structure of membranes and gesture transduction. The higher exposure to electromagnetic field increases PKC-alpha and this larger release from membranes cannot be controlled. It was concluded that greater exposure to the electromagnetic field is dangerous and had a severe impact on T-cells growth and lung cells growth and due to this greater possibility of leukemia occurrence. We show a similar effect of electromagnetic fields single celled bacteria to compare the bacterial cellular growth with the human cells using the bacteria strains which are commonly found in human body.

  12. Cell activation and cellular-cellular interactions during hemodialysis: effect of dialyzer membrane.

    PubMed

    Sirolli, V; Ballone, E; Di Stante, S; Amoroso, L; Bonomini, M

    2002-06-01

    During hemodialysis (HD), circulating blood cells can be activated and also engage in dynamic interplay. These phenomena may be important factors behind dialysis membrane bio(in)compatibility. In the present prospective cross-over study, we have used flow cytometry to evaluate the influence of different dialysis membranes on the activation of circulating blood cells (leukocytes, platelets) and their dynamic interactions (formation of circulating platelet-leukocyte and platelet-erythrocyte aggregates) during in vivo HD. Each patient (n = 10) was treated with dialyzers containing membranes of cellulose diacetate, polysulfone and ethylenevinylalcohol (EVAL) in a randomized order. Upregulation of adhesion receptor expression (CD15s, CD11b/CD18) occurred mainly with the cellulosic membrane, though an increase in CD11b/CD18 circulating on neutrophils was also found with both synthetic membranes. Circulating activated platelets (P-selectin/CD63-positive platelets) increased during HD sessions with cellulose diacetate and polysulfone. An increased formation of platelet-neutrophil aggregates was found at 15 and 30 min during dialysis with cellulose diacetate and polysulfone but not with EVAL. Platelet-erythrocyte aggregates also increased with cellulose diacetate and at 15 min with polysulfone as well. Generally in concomitance with the increase in platelet-neutrophil coaggregates, there was an increased hydrogen peroxide production by neutrophils. The results of this study indicate that cellular mechanisms can be activated during HD largely depending on the membrane material, EVAL causing less reactivity than the other two membranes. It appears that each dialysis membrane has multiple and different characteristics that may contribute to interactions with blood components. Our results also indicate that derivatizing cellulose (cellulose diacetate) may be a useful way to improve the biocompatibility of the cellulose polymer and that there may be great variability in the

  13. Cellular antioxidant effects of atorvastatin in vitro and in vivo.

    PubMed

    Wassmann, Sven; Laufs, Ulrich; Müller, Kirsten; Konkol, Christian; Ahlbory, Katja; Bäumer, Anselm T; Linz, Wolfgang; Böhm, Michael; Nickenig, Georg

    2002-02-01

    3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may exert direct effects on vascular cells and beneficially influence endothelial dysfunction. Because reactive oxygen species (ROS) may lead to vascular damage and dysfunction, we investigated the effect of atorvastatin on ROS production and the underlying mechanisms in vitro and in vivo. Cultured rat aortic vascular smooth muscle cells were incubated with 10 micromol/L atorvastatin. Angiotensin II-induced and epidermal growth factor-induced ROS production were significantly reduced by atorvastatin (dichlorofluorescein fluorescence laser microscopy). Atorvastatin downregulated mRNA expression of the NAD(P)H oxidase subunit nox1, whereas p22phox mRNA expression was not significantly altered (reverse transcription-polymerase chain reaction, Northern analysis). Membrane translocation of rac1 GTPase, which is required for the activation of NAD(P)H oxidase, was inhibited by atorvastatin (Western blot). mRNA expression of superoxide dismutase isoforms and glutathione peroxidase was not modified by atorvastatin, whereas catalase expression was upregulated at mRNA and protein levels, resulting in an increased enzymatic activity. Effects of atorvastatin on ROS production and nox1, rac1, and catalase expression were inhibited by L-mevalonate but not by 25-hydroxycholesterol. In addition, spontaneously hypertensive rats were treated with atorvastatin for 30 days. ROS production in aortic segments was significantly reduced in statin-treated rats (lucigenin chemiluminescence). Treatment with atorvastatin reduced vascular mRNA expression of p22phox and nox1 and increased aortic catalase expression. mRNA expression of superoxide dismutases, glutathione peroxidase, and NAD(P)H oxidase subunits gp91phox, p40phox, p47phox, and p67phox remained unchanged. Translocation of rac1 from the cytosol to the cell membrane was also reduced in vivo. Thus, atorvastatin exerts cellular antioxidant effects in cultured rat

  14. TopBP1 deficiency causes an early embryonic lethality and induces cellular senescence in primary cells.

    PubMed

    Jeon, Yoon; Ko, Eun; Lee, Kyung Yong; Ko, Min Ji; Park, Seo Young; Kang, Jeeheon; Jeon, Chang Hwan; Lee, Ho; Hwang, Deog Su

    2011-02-18

    TopBP1 plays important roles in chromosome replication, DNA damage response, and other cellular regulatory functions in vertebrates. Although the roles of TopBP1 have been studied mostly in cancer cell lines, its physiological function remains unclear in mice and untransformed cells. We generated conditional knock-out mice in which exons 5 and 6 of the TopBP1 gene are flanked by loxP sequences. Although TopBP1-deficient embryos developed to the blastocyst stage, no homozygous mutant embryos were recovered at E8.5 or beyond, and completely resorbed embryos were frequent at E7.5, indicating that mutant embryos tend to die at the peri-implantation stage. This finding indicated that TopBP1 is essential for cell proliferation during early embryogenesis. Ablation of TopBP1 in TopBP1(flox/flox) mouse embryonic fibroblasts and 3T3 cells using Cre recombinase-expressing retrovirus arrests cell cycle progression at the G(1), S, and G(2)/M phases. The TopBP1-ablated mouse cells exhibit phosphorylation of H2AX and Chk2, indicating that the cells contain DNA breaks. The TopBP1-ablated mouse cells enter cellular senescence. Although RNA interference-mediated knockdown of TopBP1 induced cellular senescence in human primary cells, it induced apoptosis in cancer cells. Therefore, TopBP1 deficiency in untransformed mouse and human primary cells induces cellular senescence rather than apoptosis. These results indicate that TopBP1 is essential for cell proliferation and maintenance of chromosomal integrity.

  15. Cellular internalization, transcellular transport, and cellular effects of silver nanoparticles in polarized Caco-2 cells following apical or basolateral exposure

    SciTech Connect

    Imai, Shunji; Morishita, Yuki; Hata, Tomoyuki

    When considering the safety of ingested nanomaterials, it is important to quantitate their transfer across intestinal cells; however, little information exists about the effects of nanomaterial size or exposure side (apical versus basolateral epithelial surface) on nanomaterial transfer. Here, we examined cellular internalization and transcellular transport, and the effects of nanomaterials on Caco-2 monolayers after apical or basolateral exposure to Ag or Au nanoparticles with various sizes. After apical treatment, both internalization and transfer to the basolateral side of the monolayers were greater for smaller Ag nanoparticles than for larger Ag nanoparticles. In contrast, after basolateral treatment, larger Ag nanoparticlesmore » were more internalized than smaller Ag nanoparticles, but the transfer to the apical side was greater for smaller Ag nanoparticles. Au nanoparticles showed different rules of internalization and transcellular transport compared with Ag nanoparticles. Furthermore, the paracellular permeability of the Caco-2 monolayers was temporarily increased by Ag nanoparticles (5 μg/mL; diameters, ≤10 nm) following basolateral but not apical exposure. We conclude that the internalization, transfer, and effects of nanomaterials in epithelial cell monolayers depend on the size and composition of nanomaterials, and the exposure side. - Highlights: • Ag and Au nanoparticles can transfer across Caco-2 monolayers. • Cellular uptake of nanoparticles change between apical and basolateral exposure. • Basolateral Ag nanoparticle exposure increases the permeability of Caco-2 monolayers.« less

  16. Cellular homeoproteins, SATB1 and CDP, bind to the unique region between the human cytomegalovirus UL127 and major immediate-early genes

    SciTech Connect

    Lee Jialing; Klase, Zachary; Gao Xiaoqi

    An AT-rich region of the human cytomegalovirus (CMV) genome between the UL127 open reading frame and the major immediate-early (MIE) enhancer is referred to as the unique region (UR). It has been shown that the UR represses activation of transcription from the UL127 promoter and functions as a boundary between the divergent UL127 and MIE genes during human CMV infection [Angulo, A., Kerry, D., Huang, H., Borst, E.M., Razinsky, A., Wu, J., Hobom, U., Messerle, M., Ghazal, P., 2000. Identification of a boundary domain adjacent to the potent human cytomegalovirus enhancer that represses transcription of the divergent UL127 promoter. J.more » Virol. 74 (6), 2826-2839; Lundquist, C.A., Meier, J.L., Stinski, M.F., 1999. A strong negative transcriptional regulatory region between the human cytomegalovirus UL127 gene and the major immediate-early enhancer. J. Virol. 73 (11), 9039-9052]. A putative forkhead box-like (FOX-like) site, AAATCAATATT, was identified in the UR and found to play a key role in repression of the UL127 promoter in recombinant virus-infected cells [Lashmit, P.E., Lundquist, C.A., Meier, J.L., Stinski, M.F., 2004. Cellular repressor inhibits human cytomegalovirus transcription from the UL127 promoter. J. Virol. 78 (10), 5113-5123]. However, the cellular factors which associate with the UR and FOX-like region remain to be determined. We reported previously that pancreatic-duodenal homeobox factor-1 (PDX1) bound to a 45-bp element located within the UR [Chao, S.H., Harada, J.N., Hyndman, F., Gao, X., Nelson, C.G., Chanda, S.K., Caldwell, J.S., 2004. PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of Human Cytomegalovirus Immediate Early Promoter. J. Biol. Chem. 279 (16), 16111-16120]. Here we demonstrate that two additional cellular homeoproteins, special AT-rich sequence binding protein 1 (SATB1) and CCAAT displacement protein (CDP), bind to the human CMV UR in vitro and in vivo. Furthermore, CDP is identified as a FOX-like binding

  17. Early Passage Dependence of Mesenchymal Stem Cell Mechanics Influences Cellular Invasion and Migration.

    PubMed

    Spagnol, Stephen T; Lin, Wei-Chun; Booth, Elizabeth A; Ladoux, Benoit; Lazarus, Hillard M; Dahl, Kris Noel

    2016-07-01

    The cellular structures and mechanical properties of human mesenchymal stem cells (hMSCs) vary significantly during culture and with differentiation. Previously, studies to measure mechanics have provided divergent results using different quantitative parameters and mechanical models of deformation. Here, we examine hMSCs prepared for clinical use and subject them to mechanical testing conducive to the relevant deformability associated with clinical injection procedures. Micropipette aspiration of hMSCs shows deformation as a viscoelastic fluid, with little variation from cell to cell within a population. After two passages, hMSCs deform as viscoelastic solids. Further, for clinical applicability during stem cell migration in vivo, we investigated the ability of hMSCs to invade into micropillar arrays of increasing confinement from 12 to 8 μm spacing between adjacent micropillars. We find that hMSC samples with reduced deformability and cells that are more solid-like with passage are more easily able to enter the micropillar arrays. Increased cell fluidity is an advantage for injection procedures and optimization of cell selection based on mechanical properties may enhance efficacy of injected hMSC populations. However, the ability to invade and migrate within tight interstitial spaces appears to be increased with a more solidified cytoskeleton, likely from increased force generation and contractility. Thus, there may be a balance between optimal injection survival and in situ tissue invasion.

  18. The early cellular signatures of protective immunity induced by live viral vaccination.

    PubMed

    Kohler, Siegfried; Bethke, Nicole; Böthe, Matthias; Sommerick, Sophie; Frentsch, Marco; Romagnani, Chiara; Niedrig, Matthias; Thiel, Andreas

    2012-09-01

    Here, we have used primary vaccination of healthy donors with attenuated live yellow fever virus 17D (YFV-17D) as a model to study the generation of protective immunity. In short intervals after vaccination, we analyzed the induction of YFV-17D specific T- and B-cell immunity, bystander activation, dendritic cell subsets, changes in serum cytokine levels, and YFV-17D-specific antibodies. We show activation of innate immunity and a concomitant decline of numbers of peripheral blood T and B cells. An early peak of antigen-specific T cells at day 2, followed by mobilization of innate immune cells, preceded the development of maximal adaptive immunity against YFV-17D at day 14 after vaccination. Interestingly, potent adaptive immunity as measured by high titers of neutralizing YFV-17D-specific antibodies, correlated with early activation and recruitment of YFV-17D-specific CD4(+) T cells and higher levels of sIL-6R. Thus our data might provide new insights into the interplay of innate and adaptive immunity for the induction of protective immunity. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

    PubMed Central

    Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

    2013-01-01

    Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

  20. Overexpression of the base excision repair NTHL1 glycosylase causes genomic instability and early cellular hallmarks of cancer

    PubMed Central

    Limpose, Kristin L; Trego, Kelly S; Li, Zhentian; Leung, Sara W; Sarker, Altaf H; Shah, Jason A; Ramalingam, Suresh S; Werner, Erica M; Dynan, William S; Cooper, Priscilla K; Corbett, Anita H; Doetsch, Paul W

    2018-01-01

    Abstract Base excision repair (BER), which is initiated by DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. The NTHL1 glycosylase, which excises DNA base damage caused by reactive oxygen species, is thought to be a tumor suppressor. However, in addition to NTHL1 loss-of-function mutations, our analysis of cancer genomic datasets reveals that NTHL1 frequently undergoes amplification or upregulation in some cancers. Whether NTHL1 overexpression could contribute to cancer phenotypes has not yet been explored. To address the functional consequences of NTHL1 overexpression, we employed transient overexpression. Both NTHL1 and a catalytically-dead NTHL1 (CATmut) induce DNA damage and genomic instability in non-transformed human bronchial epithelial cells (HBEC) when overexpressed. Strikingly, overexpression of either NTHL1 or CATmut causes replication stress signaling and a decrease in homologous recombination (HR). HBEC cells that overexpress NTHL1 or CATmut acquire the ability to grow in soft agar and exhibit loss of contact inhibition, suggesting that a mechanism independent of NTHL1 catalytic activity contributes to acquisition of cancer-related cellular phenotypes. We provide evidence that NTHL1 interacts with the multifunctional DNA repair protein XPG suggesting that interference with HR is a possible mechanism that contributes to acquisition of early cellular hallmarks of cancer. PMID:29522130

  1. A fresh look at the fossil evidence for early Archaean cellular life

    PubMed Central

    Brasier, Martin; McLoughlin, Nicola; Green, Owen; Wacey, David

    2006-01-01

    The rock record provides us with unique evidence for testing models as to when and where cellular life first appeared on Earth. Its study, however, requires caution. The biogenicity of stromatolites and ‘microfossils’ older than 3.0 Gyr should not be accepted without critical analysis of morphospace and context, using multiple modern techniques, plus rejection of alternative non-biological (null) hypotheses. The previous view that the co-occurrence of biology-like morphology and carbonaceous chemistry in ancient, microfossil-like objects is a presumptive indicator of biogenicity is not enough. As with the famous Martian microfossils, we need to ask not ‘what do these structures remind us of?’, but ‘what are these structures?’ Earth's oldest putative ‘microfossil’ assemblages within 3.4–3.5 Gyr carbonaceous cherts, such as the Apex Chert, are likewise self-organizing structures that do not pass tests for biogenicity. There is a preservational paradox in the fossil record prior to ca 2.7 Gyr: suitable rocks (e.g. isotopically light carbonaceous cherts) are widely present, but signals of life are enigmatic and hard to decipher. One new approach includes detailed mapping of well-preserved sandstone grains in the ca 3.4 Gyr Strelley Pool Chert. These can contain endolithic microtubes showing syngenicity, grain selectivity and several levels of geochemical processing. Preliminary studies invite comparison with a class of ambient inclusion trails of putative microbial origin and with the activities of modern anaerobic proteobacteria and volcanic glass euendoliths. PMID:16754605

  2. The effect of zinc on cellular immunity in chronic uremia.

    PubMed

    Antoniou, L D; Shalhoub, R J; Schechter, G P

    1981-09-01

    Delayed hypersensitivity to mumps was examined in 25 apparently well-nourished men receiving regular hemodialysis, each of whom had a history of mumps. A positive reaction was observed in eight of nine patients already under therapy with zinc added to the dialysis bath. In contrast, 11 of 16 untreated patients were anergic. Four of the anergic patients were subsequently treated with zinc resulting in restoration of sensitivity in three patients. There were no significant differences in lymphocyte, monocyte, or T-cell counts between the two groups of patients. Consequently, zinc probably acts by improving the function of one or more of these cell types. Protracted zinc deficiency may be a major cause of impaired cellular immunity in chronic renal failure.

  3. Cellular and Molecular effects of Vitamin D on Carcinogenesis

    PubMed Central

    Welsh, JoEllen

    2011-01-01

    Epidemiologic data suggest that the incidence and severity of many types of cancer inversely correlates with indices of vitamin D status. The vitamin D receptor (VDR) is highly expressed in epithelial cells at risk for carcinogenesis including those resident in skin, breast, prostate and colon, providing a direct molecular link by which vitamin D status impacts on carcinogenesis. Consistent with this concept, activation of VDR by its ligand 1,25-dihydroxyvitamin D (1,25D) triggers comprehensive genomic changes in epithelial cells that contribute to maintenance of the differentiated phenotype, resistance to cellular stresses and protection of the genome. Many epithelial cells also express the vitamin D metabolizing enzyme CYP27B1 which enables autocrine generation of 1,25D from the circulating vitamin D metabolite 25-hydroxyvitamin D (25D), critically linking overall vitamin D status with cellular anti-tumor actions. Furthermore, pre-clinical studies in animal models has demonstrated that dietary supplementation with vitamin D or chronic treatment with VDR agonists decreases tumor development in skin, colon, prostate and breast. Conversely, deletion of the VDR gene in mice alters the balance between proliferation and apoptosis, increases oxidative DNA damage, and enhances susceptibility to carcinogenesis in these tissues. Because VDR expression is retained in many human tumors, vitamin D status may be an important modulator of cancer progression in persons living with cancer. Collectively, these observations have reinforced the need to further define the molecular actions of the VDR and the human requirement for vitamin D in relation to cancer development and progression. PMID:22085499

  4. Early changes in staurosporine-induced differentiated RGC-5 cells indicate cellular injury response to nonlethal blue light exposure.

    PubMed

    Zhang, Pei; Huang, Chen; Wang, Wei; Wang, Minshu

    2015-06-01

    damage of staurosporine-differentiated RGC-5 cells. These increases in oxidative stress and mitochondrial content were the early steps of the cellular response to the exposure of relatively low doses (10 J cm(-2)) of blue light.

  5. Cord blood Streptococcus pneumoniae‐specific cellular immune responses predict early pneumococcal carriage in high‐risk infants in Papua New Guinea

    PubMed Central

    Francis, J. P.; Richmond, P. C.; Strickland, D.; Prescott, S. L.; Pomat, W. S.; Michael, A.; Nadal‐Sims, M. A.; Edwards‐Devitt, C. J.; Holt, P. G.; Lehmann, D.

    2016-01-01

    Summary In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high‐risk areas have pre‐existing pneumococcal‐specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA‐induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA‐specific interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, interleukin (IL)‐5, IL‐6, IL‐10 and IL‐13 responses, and lower dPly‐IL‐6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA‐IL‐5 and PspA‐IL‐13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly‐IL‐6 responses with a higher frequency of cord antigen‐presenting cells. In the PNG cohort, higher PspA‐specific IL‐5 and IL‐6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA‐IL‐10 CBMC responses. Pneumococcus‐specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease. PMID:27859014

  6. How-to-Do-It: Demonstrating the Effects of Stress on Cellular Membranes.

    ERIC Educational Resources Information Center

    Vodopich, Darrell S.; Moore, Randy

    1989-01-01

    Describes two simple procedures allowing students to experiment with living membranes and to relate their results to fundamental membrane structure. Provides instructions for determining the effects of temperature and organic solvent stress on cellular membranes, and spectrophotometric analysis. (RT)

  7. Effects of magnitude, depth, and time on cellular seismology forecasts

    NASA Astrophysics Data System (ADS)

    Fisher, Steven Wolf

    This study finds that, in most cases analyzed to date, past seismicity tends to delineate zones where future earthquakes are likely to occur. Network seismicity catalogs for the New Madrid Seismic Zone (NMSZ), Australia (AUS), California (CA), and Alaska (AK) are analyzed using modified versions of the Cellular Seismology (CS) method of Kafka (2002, 2007). The percentage of later occurring earthquakes located near earlier occurring earthquakes typically exceeds the expected percentage for randomly distributed later occurring earthquakes, and the specific percentage is influenced by several variables, including magnitude, depth, time, and tectonic setting. At 33% map area coverage, hit percents are typically 85-95% in the NMSZ, 50-60% in AUS, 75-85% in CA, and 75-85% in AK. Statistical significance testing is performed on trials analyzing the same variables so that the overall regions can be compared, although some tests are inconclusive due to the small number of earthquake sample sizes. These results offer useful insights into understanding the capabilities and limits of CS studies, which can provide guidance for improving the seismicity-based components of seismic hazard assessments.

  8. The effect of surface functionality on cellular trafficking of dendrimers.

    PubMed

    Perumal, Omathanu P; Inapagolla, Rajyalakshmi; Kannan, Sujatha; Kannan, Rangaramanujam M

    2008-01-01

    Dendrimers are an emerging group of nanostructured, polymeric biomaterials that have potential as non-viral vehicles for delivering drugs and genetic material to intracellular targets. They have a high charge density with tunable surface functional groups, which can alter the local environment and influence cellular interactions. This can have a significant impact on the intracellular trafficking of dendrimer-based nanodevices. With the help of flow cytometry, fluorescence microscopy, and by using specific inhibitors, the influence of surface functionality on their uptake in A549 lung epithelial cells, and subsequent intracellular distribution was investigated. In this paper, we have shown that even though all the dendrimers are taken up by fluid-phase endocytosis, significant differences in uptake mechanisms exist. Anionic dendrimers appear to be mainly taken up by caveolae mediated endocytosis in A549 lung epithelial cells, while cationic and neutral dendrimers appear to be taken in by a non-clathrin, non-caveolae mediated mechanism that may be by electrostatic interactions or other non-specific fluid-phase endocytosis. These findings open up new possibilities of targeting therapeutic agents to specific cell organelles based on surface charge.

  9. Early cellular responses against tributyltin chloride exposure in primary cultures derived from various brain regions.

    PubMed

    Mitra, Sumonto; Siddiqui, Waseem A; Khandelwal, Shashi

    2014-05-01

    Tributyltin (TBT) is a potent biocide and commonly used in various industrial sectors. Humans are mainly exposed through the food chain. We have previously demonstrated tin accumulation in brain following TBT-chloride (TBTC) exposure. In this study, effect of TBTC on dissociated cells from different brain regions was evaluated. Cytotoxicity assay (MTT), mode of cell death (Annexin V/PI assay), oxidative stress parameters (ROS and lipid peroxidation), reducing power of the cell (GSH), mitochondrial membrane potential (MMP) and intracellular Ca(2+) were evaluated to ascertain the effect of TBTC. Expression of glial fibrillary acidic protein (GFAP) was measured to understand the effect on astroglial cells. TBTC as low as 30 nM was found to reduce GSH levels, whereas higher doses of 300 and 3000 nM induced ROS generation and marked loss in cell viability mainly through apoptosis. Striatum showed higher susceptibility than other regions, which may have further implications on various neurological aspects. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Effect of Boron Doping on Cellular Discontinuous Precipitation for Age-Hardenable Cu–Ti Alloys

    PubMed Central

    Semboshi, Satoshi; Ikeda, Jun; Iwase, Akihiro; Takasugi, Takayuki; Suzuki, Shigeru

    2015-01-01

    The effects of boron doping on the microstructural evolution and mechanical and electrical properties of age-hardenable Cu–4Ti (at.%) alloys are investigated. In the quenched Cu–4Ti–0.03B (at.%) alloy, elemental B (boron) is preferentially segregated at the grain boundaries of the supersaturated solid-solution phase. The aging behavior of the B-doped alloy is mostly similar to that of conventional age-hardenable Cu–Ti alloys. In the early stage of aging at 450 °C, metastable β′-Cu4Ti with fine needle-shaped precipitates continuously form in the matrix phase. Cellular discontinuous precipitates composed of the stable β-Cu4Ti and solid-solution laminates are then formed and grown at the grain boundaries. However, the volume fraction of the discontinuous precipitates is lower in the Cu–4Ti–0.03B alloy than the Cu–4Ti alloy, particularly in the over-aging period of 72–120 h. The suppression of the formation of discontinuous precipitates eventually results in improvement of the hardness and tensile strength. It should be noted that minor B doping of Cu–Ti alloys also effectively enhances the elongation to fracture, which should be attributed to segregation of B at the grain boundaries.

  11. Early metabolic/cellular-level resuscitation following terminal brain stem herniation: implications for organ transplantation.

    PubMed

    Arbour, Richard B

    2013-01-01

    Patients with terminal brain stem herniation experience global physiological consequences and represent a challenging population in critical care practice as a result of multiple factors. The first factor is severe depression of consciousness, with resulting compromise in airway stability and lung ventilation. Second, with increasing severity of brain trauma, progressive brain edema, mass effect, herniation syndromes, and subsequent distortion/displacement of the brain stem follow. Third, with progression of intracranial pathophysiology to terminal brain stem herniation, multisystem consequences occur, including dysfunction of the hypothalamic-pituitary axis, depletion of stress hormones, and decreased thyroid hormone bioavailability as well as biphasic cardiovascular state. Cardiovascular dysfunction in phase 1 is a hyperdynamic and hypertensive state characterized by elevated systemic vascular resistance and cardiac contractility. Cardiovascular dysfunction in phase 2 is a hypotensive state characterized by decreased systemic vascular resistance and tissue perfusion. Rapid changes along the continuum of hyperperfusion versus hypoperfusion increase risk of end-organ damage, specifically pulmonary dysfunction from hemodynamic stress and high-flow states as well as ischemic changes consequent to low-flow states. A pronounced inflammatory state occurs, affecting pulmonary function and gas exchange and contributing to hemodynamic instability as a result of additional vasodilatation. Coagulopathy also occurs as a result of consumption of clotting factors as well as dilution of clotting factors and platelets consequent to aggressive crystalloid administration. Each consequence of terminal brain stem injury complicates clinical management within this patient demographic. In general, these multisystem consequences are managed with mechanism-based interventions within the context of caring for the donor's organs (liver, kidneys, heart, etc.) after death by neurological

  12. Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma.

    PubMed

    Dhabhar, Firdaus S; Saul, Alison N; Daugherty, Christine; Holmes, Tyson H; Bouley, Donna M; Oberyszyn, Tatiana M

    2010-01-01

    In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposure would enhance protective immunity and increase resistance to SCC. Control and short-term stress groups were treated identically except that the short-term stress group was restrained (2.5h) before each of nine UV-exposure sessions (minimum erythemal dose, 3-times/week) during weeks 4-6 of the 10-week UV exposure protocol. Tumors were measured weekly, and tissue collected at weeks 7, 20, and 32. Chemokine and cytokine gene expression was quantified by real-time PCR, and CD4+ and CD8+ T cells by flow cytometry and immunohistochemistry. Compared to controls, the short-term stress group showed greater cutaneous T-cell attracting chemokine (CTACK)/CCL27, RANTES, IL-12, and IFN-gamma gene expression at weeks 7, 20, and 32, higher skin infiltrating T cell numbers (weeks 7 and 20), lower tumor incidence (weeks 11-20) and fewer tumors (weeks 11-26). These results suggest that activation of short-term stress physiology increased chemokine expression and T cell trafficking and/or function during/following UV exposure, and enhanced Type 1 cytokine-driven cell-mediated immunity that is crucial for resistance to SCC. Therefore, the physiological fight-or-flight stress response and its adjuvant-like immuno-enhancing effects, may provide a novel and important mechanism for enhancing immune system mediated tumor-detection/elimination that merits further investigation.

  13. Cellular and Physiological Effects of Anthrax Exotoxin and Its Relevance to Disease

    PubMed Central

    Lowe, David E.; Glomski, Ian J.

    2012-01-01

    Bacillus anthracis, the causative agent of anthrax, secretes a tri-partite exotoxin that exerts pleiotropic effects on the host. The purification of the exotoxin components, protective antigen, lethal factor, and edema factor allowed the rapid characterization of their physiologic effects on the host. As molecular biology matured, interest focused on the molecular mechanisms and cellular alterations induced by intoxication. Only recently have researchers begun to connect molecular and cellular knowledge back to the broader physiological effects of the exotoxin. This review focuses on the progress that has been made bridging molecular knowledge back to the exotoxin’s physiological effects on the host. PMID:22919667

  14. Molecular and Cellular Mechanisms of Muscle Aging and Sarcopenia and Effects of Electrical Stimulation in Seniors.

    PubMed

    Barber, Laura; Scicchitano, Bianca Maria; Musaro, Antonio

    2015-08-24

    The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. It is generally accepted that cumulative failure to repair damage related to an overall decrease in anabolic processes is a primary cause of functional impairment in muscle. The functional performance of skeletal muscle tissues declines during post- natal life and it is compromised in different diseases, due to an alteration in muscle fiber composition and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue. Characteristics of skeletal muscle aging and diseases include a conspicuous reduction in myofiber plasticity (due to the progressive loss of muscle mass and in particular of the most powerful fast fibers), alteration in muscle-specific transcriptional mechanisms, and muscle atrophy. An early decrease in protein synthetic rates is followed by a later increase in protein degradation, to affect biochemical, physiological, and morphological parameters of muscle fibers during the aging process. Alterations in regenerative pathways also compromise the functionality of muscle tissues. In this review we will give an overview of the work on molecular and cellular mechanisms of aging and sarcopenia and the effects of electrical stimulation in seniors..

  15. In vitro effects of platinum compounds on renal cellular respiration in mice.

    PubMed

    Almarzooqi, Saeeda-S; Alfazari, Ali-S; Abdul-Kader, Hidaya-M; Saraswathiamma, Dhanya; Albawardi, Alia-S; Souid, Abdul-Kader

    2015-01-01

    Cisplatin, carboplatin and oxaliplatin are structurally-related compounds, which are commonly used in cancer therapy. Cisplatin (Platinol(®)) has Boxed Warning stating: "Cumulative renal toxicity associated with PLATINOL is severe", while carboplatin and oxaliplatin are less nephrotoxic. These drugs form platinum adducts with cellular DNA. Their bindings to cellular thiols (e.g., glutathione and metallothionein) are known to contribute to drug resistance while thiol depletion augments platinum toxicity. Using phosphorescence oxygen analyzer, this study investigated the effects of platinum drugs on renal cellular respiration (mitochondrial O2 consumption) in the presence and absence of the thiol blocking agent N-ethylmaleimide (used here as a model for thiol depletion). Renal cellular ATP was also determined. Kidney fragments from C57BL/6 mice were incubated at 37 °C in Krebs-Henseleit buffer (gassed with 95% O2:5% CO2) with and without 100 μM platinum drug in the presence and absence of 100 μM N-ethylmaleimide for ≤ 6 h. Platinum drugs alone had no effects on cellular respiration (P ≥ 0.143) or ATP (P ≥ 0.161). N-ethylmaleimide lowered cellular respiration (P ≤ 0.114) and ATP (P = 0.008). The combination of platinum drug and N-ethylmaleimide significantly lowered both cellular respiration (P ≤ 0.006) and ATP (P ≤ 0.003). Incubations with N-ethylmaleimide alone were associated with moderate-to-severe tubular necrosis. Incubations with cisplatin+N-ethylmaleimide vs. cisplatin alone produced similar severities of tubular necrosis. Tubular derangements were more prominent in carboplatin+N-ethylmaleimide vs. carboplatin alone and in oxaliplatin+N-ethylmaleimide vs. oxaliplatin alone. These results demonstrate the adverse events of thiol depletion on platinum-induced nephrotoxicities. The results suggest cellular bioenergetics is a useful surrogate biomarker for assessing drug-induced nephrotoxicities.

  16. Early cellular evolution.

    NASA Technical Reports Server (NTRS)

    Margulis, L.

    1972-01-01

    Study of the evolutionary developments that occurred subsequent to the origin of ancestral cells. Microbial physiology and ecology are potential sharp tools for shaping concepts of microbial evolution. Some popular unjustified assumptions are discussed. It is considered that certain principles derived mainly from the advances of molecular biology can be used to order the natural groups (genera) of extant prokaryotes and their patterns phylogenetically.

  17. HTLV-1 Tax Effects on Cellular Mitotic Regulation

    DTIC Science & Technology

    2007-04-12

    39 2 MutagenesisTax mutagenesis and selection for tax mutants...43 Isolation of tax mutants that do not cause growth arrest in S. cerevisiae. .......... 43 Tax mutants selected in W303a are functional in...114). One currently-approved therapeutic agent , Indinavir, is an effective inhibitor of both proteases. New protease inhibitors are currently being

  18. The effects of carbon nanotubes on lung and dermal cellular behaviors

    PubMed Central

    Luanpitpong, Sudjit; Wang, Liying; Rojanasakul, Yon

    2016-01-01

    Carbon nanotubes (CNTs) hold great promise to create new and better products, but their adverse health effect is a major concern. Human exposure to CNTs is primarily through inhalation and dermal contact, especially during the manufacturing and handling processes. Numerous animal studies have demonstrated the potential pulmonary and dermal hazards associated with CNT exposure, while in vitro studies have assessed the effects of CNT exposure on various cellular behaviors and have been used to perform mechanistic studies. In this review, we provide an overview of the pathological effects of CNTs and examine the acute and chronic effects of CNT exposure on lung and dermal cellular behaviors, beyond the generally discussed cytotoxicity. We then examine the linkage of cellular behaviors and disease pathogenesis, and discuss the pertinent mechanisms. PMID:24981653

  19. Antiarrhythmic effect of IKr activation in a cellular model of LQT3.

    PubMed

    Diness, Jonas Goldin; Hansen, Rie Schultz; Nissen, Jakob Dahl; Jespersen, Thomas; Grunnet, Morten

    2009-01-01

    Long QT syndrome type 3 (LQT3) is an inherited cardiac disorder caused by gain-of-function mutations in the cardiac voltage-gated sodium channel, Na(v)1.5. LQT3 is associated with the polymorphic ventricular tachycardia torsades de pointes (TdP), which can lead to syncope and sudden cardiac death. The sea anemone toxin ATX-II has been shown to inhibit the inactivation of Na(v)1.5, thereby closely mimicking the underlying cause of LQT3 in patients. The hypothesis for this study was that activation of the I(Kr) current could counteract the proarrhythmic effects of ATX-II. Two different activators of I(Kr), NS3623 and mallotoxin (MTX), were used in patch clamp studies of ventricular cardiac myocytes acutely isolated from guinea pig to test the effects of selective I(Kr) activation alone and in the presence of ATX-II. Action potentials were elicited at 1 Hz by current injection and the cells were kept at 32 degrees C to 35 degrees C. NS3623 significantly shortened action potential duration at 90% repolarization (APD(90)) compared with controls in a dose-dependent manner. Furthermore, it reduced triangulation, which is potentially antiarrhythmic. Application of ATX-II (10 nM) was proarrhythmic, causing a profound increase of APD(90) as well as early afterdepolarizations and increased beat-to-beat variability. Two independent I(Kr) activators attenuated the proarrhythmic effects of ATX-II. NS3623 did not affect the late sodium current (I(NaL)) in the presence of ATX-II. Thus, the antiarrhythmic effect of NS3623 is likely to be caused by selective I(Kr) activation. The present data show the antiarrhythmic potential of selective I(Kr) activation in a cellular model of the LQT3 syndrome.

  20. Rays Sting: The Acute Cellular Effects of Ionizing Radiation Exposure

    PubMed Central

    Franco, A; Ciccarelli, M; Sorriento, D; Napolitano, L; Fiordelisi, A; Trimarco, B; Durante, M; Iaccarino, G

    2016-01-01

    High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism. PMID:27326395

  1. Effect of surface tension anisotropy on cellular morphologies

    NASA Technical Reports Server (NTRS)

    Mcfadden, G. B.; Coriell, S. R.; Sekerka, R. F.

    1988-01-01

    A three-dimensional weakly nonlinear analysis for conditions near the onset of instability at the crystal-melt interface was carried out to second order, taking into account the effects of latent heat generation and surface-tension anisotropy of the crystal-melt interface; particular consideration was given to the growth of a cubic crystal in the 001-, 011-, and 111-line directions. Numerical calculations by McFadden et al. (1987), performed for an aluminum-chromium alloy with the assumption of a linear temperature field and an isotropic surface tension, showed that only hexagonal nodes (and not hexagonal cells) occurred near the onset of instability. The results of the present analysis indicate that the nonlinear temperature field (which occurs when thermal conductivities of the crystal and the melt are different and/or the latent heat effects are not negligible) can modify this result and, for certain alloys and processing conditions, can cause the occurrence of hexagonal cells near the onset of instability.

  2. Gravitational Effects on Closed-Cellular-Foam Microstructure

    NASA Technical Reports Server (NTRS)

    Noever, David A.; Cronise, Raymond J.; Wessling, Francis C.; McMannus, Samuel P.; Mathews, John; Patel, Darayas

    1996-01-01

    Polyurethane foam has been produced in low gravity for the first time. The cause and distribution of different void or pore sizes are elucidated from direct comparison of unit-gravity and low-gravity samples. Low gravity is found to increase the pore roundness by 17% and reduce the void size by 50%. The standard deviation for pores becomes narrower (a more homogeneous foam is produced) in low gravity. Both a Gaussian and a Weibull model fail to describe the statistical distribution of void areas, and hence the governing dynamics do not combine small voids in either a uniform or a dependent fashion to make larger voids. Instead, the void areas follow an exponential law, which effectively randomizes the production of void sizes in a nondependent fashion consistent more with single nucleation than with multiple or combining events.

  3. On the effect of memory in a quantum prisoner's dilemma cellular automaton

    NASA Astrophysics Data System (ADS)

    Alonso-Sanz, Ramón; Revuelta, Fabio

    2018-03-01

    The disrupting effect of quantum memory on the dynamics of a spatial quantum formulation of the iterated prisoner's dilemma game with variable entangling is studied. The game is played within a cellular automata framework, i.e., with local and synchronous interactions. The main findings of this work refer to the shrinking effect of memory on the disruption induced by noise.

  4. Effective Teachers of Early Adolescents.

    ERIC Educational Resources Information Center

    Steer, Donald R.

    Over the past 15 years a number of studies and official statements have considered characteristics and competencies of effective middle/junior high school teachers. Thirty-eight items found to be present in several studies were used to form a questionnaire, sent to 500 members of the National Middle School Association, about the importance of…

  5. Effects of reactive oxygen species on cellular wall disassembly of banana fruit during ripening.

    PubMed

    Cheng, Guiping; Duan, Xuewu; Shi, John; Lu, Wangjin; Luo, Yunbo; Jiang, Weibo; Jiang, Yueming

    2008-07-15

    Fruit softening is generally attributed to cell wall disassembly. Experiments were conducted to investigate effects of various reactive oxygen species (ROS) on in vitro cellular wall disassembly of harvested banana fruit. The alcohol-extracted insoluble residue (AEIR) was obtained from the pulp tissues of banana fruit at various ripening stages and then used to examine the disassembly of cellular wall polysaccharides in the presence of superoxide anion (O2(-)), hydrogen peroxide (H2O2) or hydroxyl radical (OH) and their scavengers. The presence of OH accelerated significantly disassembly of cellular wall polysaccharides in terms of the increase in contents of total sugars released and uronic acid, and the decrease in molecular mass of soluble polysaccharides, using gel permeation chromatography. However, the treatment with H2O2 or O2(-) showed no significant effect on the disassembly of cellular wall polysaccharides. Furthermore, the degradation of the de-esterified AEIR was more susceptible to OH attack than the esterified AEIR. In addition, the effect of OH could be inhibited in the presence of OH scavenger. This study suggests that disassembly of cellular wall polysaccharides could be initiated by OH as the solublisation of the polysaccharides increased, which, in turn, accelerated fruit softening. Copyright © 2008 Elsevier Ltd. All rights reserved.

  6. Cellular Effects of Everolimus and Sirolimus on Podocytes

    PubMed Central

    Müller-Krebs, Sandra; Weber, Lena; Tsobaneli, Julia; Kihm, Lars P.; Reiser, Jochen; Zeier, Martin; Schwenger, Vedat

    2013-01-01

    Everolimus (EVL) and Sirolimus (SRL) are potent immunosuppressant agents belonging to the group of mammalian target of rapamycin (mTOR) inhibitors used to prevent transplant rejection. However, some patients develop proteinuria following a switch from a calcineurin inhibitor regimen to mTOR inhibitors. Whether different mTOR inhibitors show similar effects on podocytes is still unknown. To analyze this, human podocytes were incubated with different doses of EVL and SRL. After incubation with EVL or SRL, podocytes revealed a reduced expression of total mTOR. Phosphorylation of p70S6K and Akt was diminished, whereas pAkt expression was more reduced in the SRL group. In both groups actin cytoskeletal reorganization was increased. Synaptopodin and podocin expression was reduced as well as nephrin protein, particularly in the SRL group. NFκB activation and IL-6 levels were lower in EVL and SRL, and even lower in SRL. Apoptosis was more increased in SRL than in the EVL group. Our data suggests that mTOR inhibitors affect podocyte integrity with respect to podocyte proteins, cytoskeleton, inflammation, and apoptosis. Our study is the first to analyze both mTOR inhibitors, EVL and SRL, in parallel in podocytes. Partially, the impact of EVL and SRL on podocytes differs. Nevertheless, it still remains unclear whether these differences are of relevance regarding to proteinuria in transplant patients. PMID:24260371

  7. The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction

    PubMed Central

    Hoshyar, Nazanin; Gray, Samantha; Han, Hongbin; Bao, Gang

    2016-01-01

    Nanoparticle-based technologies offer exciting new approaches to disease diagnostics and therapeutics. To take advantage of unique properties of nanoscale materials and structures, the size, shape and/or surface chemistry of nanoparticles need to be optimized, allowing their functionalities to be tailored for different biomedical applications. Here we review the effects of nanoparticle size on cellular interaction and in vivo pharmacokinetics, including cellular uptake, biodistribution and circulation half-life of nanoparticles. Important features of nanoparticle probes for molecular imaging and modeling of nanoparticle size effects are also discussed. PMID:27003448

  8. Early Corneal Cellular and Nerve Fiber Pathology in Young Patients With Type 1 Diabetes Mellitus Identified Using Corneal Confocal Microscopy.

    PubMed

    Szalai, Eszter; Deák, Eszter; Módis, László; Németh, Gábor; Berta, András; Nagy, Annamária; Felszeghy, Eniko; Káposzta, Rita; Malik, Rayaz A; Csutak, Adrienne

    2016-03-01

    The aim of this study was to quantify epithelial, stromal, and endothelial cell density, and subbasal nerve morphology in young patients with type 1 diabetes mellitus with and without diabetic retinopathy. A total of 28 young patients (mean age, 22.86 ± 9.05 years) with type 1 diabetes, with (n = 18) and without (n = 10) retinopathy, and 17 age-matched healthy control subjects (mean age, 26.53 ± 2.43 years) underwent corneal confocal microscopy (CCM). We found significantly lower epithelial (P < 0.0001) and endothelial (P = 0.001) cell densities and higher keratocyte cell density (P = 0.024) in patients with type 1 diabetes compared to controls. Significantly lower corneal nerve fiber density (P = 0.004), nerve branch density (P = 0.004), total nerve branch density (P = 0.04), and nerve fiber length (P = 0.001), and greater nerve fiber width (P = 0.04) were observed in patients with type 1 diabetes compared to control subjects. Significantly lower epithelial (P < 0.001) and endothelial (P = 0.02) cell densities, nerve branch density (P = 0.02), and nerve fiber length (P = 0.04), and significantly higher keratocyte cell density (P = 0.02) were found in patients with type 1 diabetes without retinopathy compared to control subjects. Corneal confocal microscopy identifies corneal cellular and small nerve fiber pathology in young patients with type 1 diabetes without retinopathy, which increases in severity in those with retinopathy. Corneal confocal microscopy appears to have considerable use as an imaging biomarker for early subclinical pathology in young patients with type 1 diabetes mellitus.

  9. Effect of Withaferin A on A549 cellular proliferation and apoptosis in non-small cell lung cancer.

    PubMed

    Cai, Yong; Sheng, Zhao-Ying; Chen, Yun; Bai, Chong

    2014-01-01

    To explore the effect of Withaferin A on A549 cellular proliferation and apoptosis in non-small cell lung cancer (NSCLC). NSCNC cell line A549 was selected to explore the effect of Withaferin A on A549 cellular proliferation, apoptosis and the PI3K/Akt signal pathway capable of regulating tumor biological behavior by assessment of cellular proliferation, cellular apoptotic rates and cellular cycling as well as by immuno-blotting. Withaferin A could inhibit A549 cellular proliferation and the control rate was dosage-dependent (P<0.05), which also increased time-dependently with the same dosage of Withaferin A (P<0.05). The apoptotic indexes in A549 cells treated with 0, 2.5, 5.0, 10.0 and 20.0 μmol·L-1 Withaferin A for 48 h were significantly different (P<0.05). In addition, the apoptotic rates of each group in both early and advanced stages were higher than those in 0 μmol·L-1 (P<0.05), which were evidently higher after 48 h than those after 24 h (P<0.05). A549 cells treated by Withaferin A for 48 h were markedly lower in Bcl-2 level and obviously higher in Bax and cleaved caspase-3 levels than those treated by 0 μmol·L-1 Withaferin A (P<0.05), and there were significant differences among 5, 10 and 20 μmol·L-1 Withaferin A (P<0.05). The ratios of A549 cells treated by Withaferin A for 48 h in G0/G1 stage were higher than those in 0 μmol·L-1 , while those in S and G2/M stages were obviously lower than those in G2/M stage, and there were significant differences in 5.0, 10.0 and 20.0 μmol·L-1 Withaferin A (P<0.05). Additionally, p-Akt/Akt values were in reverse association with dosage, and the differences were significant (P<0.05). Withaferin A can inhibit the proliferation and apoptosis of A549 cells by suppressing activation of the PI3K/Akt pathways.

  10. Effects of mild running on substantia nigra during early neurodegeneration.

    PubMed

    Almeida, Michael F; Silva, Carolliny M; Chaves, Rodrigo S; Lima, Nathan C R; Almeida, Renato S; Melo, Karla P; Demasi, Marilene; Fernandes, Tiago; Oliveira, Edilamar M; Netto, Luis E S; Cardoso, Sandra M; Ferrari, Merari F R

    2018-06-01

    Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level. It was demonstrated that moderate treadmill running, practiced during early neurodegeneration, prevented the increase of alpha-synuclein and maintained the levels of TH unaltered in substantia nigra of aged rats. Physical exercise also stimulated autophagy and prevented impairment of mitophagy, but decreased proteasome activity in rotenone-exposed aged rats. Physical activity also prevented H 2 O 2 increase during early neurodegeneration, although the involved mechanism remains to be elucidated. TrkB levels and its anterograde trafficking seem not to be influenced by moderate treadmill running. In conclusion, moderate physical training could prevent early neurodegeneration in substantia nigra through the improvement of autophagy and mitophagy.

  11. Effect of living cellular sheets on the angiogenic potential of human microvascular endothelial cells.

    PubMed

    Villar, Cristina C; Zhao, Xiang R; Livi, Carolina B; Cochran, David L

    2015-05-01

    A fundamental issue limiting the efficacy of surgical approaches designed to correct periodontal mucogingival defects is that new tissues rely on limited sources of blood supply from the adjacent recipient bed. Accordingly, therapies based on tissue engineering that leverage local self-healing potential may represent promising alternatives for the treatment of mucogingival defects by inducing local vascularization. The aim of this study is to evaluate the effect of commercially available living cellular sheets (LCS) on the angiogenic potential of neonatal dermal human microvascular endothelial cells (HMVEC-dNeo). The effect of LCS on HMVEC-dNeo proliferation, migration, capillary tube formation, gene expression, and production of angiogenic factors was evaluated over time. LCS positively influenced HMVEC-dNeo proliferation and migration. Moreover, HMVEC-dNeo incubated with LCS showed transcriptional profiles different from those of untreated cells. Whereas increased expression of angiogenic genes predominated early on in response to LCS, late-phase responses were characterized by up- and downregulation of angiostatic and angiogenic genes. However, this trend was not confirmed at the protein level, as LCS induced increased production of most of the angiogenic factors tested (i.e., epidermal growth factor [EGF], heparin-binding EGF-like growth factor, interleukin 6, angiopoietin, platelet-derived growth factor-BB, placental growth factor, and vascular endothelial growth factor) throughout the investigational period. Finally, although LCS induced HMVEC-dNeo proliferation, migration, and expression of angiogenic factors, additional factors and environmental pressures are likely to be required to promote the development of complex, mesh-like vascular structures. LCS favor initial mechanisms that govern angiogenesis but failed to enhance or accelerate HMVEC-dNeo morphologic transition to complex vascular structures.

  12. Effect of electromagnetic field emitted by cellular phones on fetal heart rate patterns.

    PubMed

    Celik, Onder; Hascalik, Seyma

    2004-01-15

    The study was planned to determine the effects of electromagnetic fields produced by cellular phones on baseline fetal heart rate, acceleration and deceleration. Forty pregnant women undergoing non-stress test were admitted to the study. Non-stress test was obtained while the subjects were holding the CP on stand by mode and on dialing mode, each for 5 min. Similar recordings were taken while there were no phones around for 10 min. Electromagnetic fields produced by cellular phones do not cause any demonstrable affect in fetal heart rate, acceleration and deceleration.

  13. Investigations of the inhibitory effects of tocopherol (vitamin E) on free radical deterioration of cellular membranes

    NASA Technical Reports Server (NTRS)

    Richardson, D.

    1975-01-01

    The inhibitory effects are investigated of d,1-alpha-tocopherol and d,1-alpha-tocopheryl acetate on the free radical deterioration of cellular membranes. The level of toxicity of d,1-alpha-tocopherol and d,1-alpha-tocopheryl acetate in mice is determined.

  14. Effects of electromagnetic radiation from a cellular phone on human sperm motility: an in vitro study.

    PubMed

    Erogul, Osman; Oztas, Emin; Yildirim, Ibrahim; Kir, Tayfun; Aydur, Emin; Komesli, Gokhan; Irkilata, Hasan Cem; Irmak, Mehmet Kemal; Peker, Ahmet Fuat

    2006-10-01

    There has been growing public concern on the effects of electromagnetic radiation (EMR) emitted by cellular phones on human health. Many studies have recently been published on this topic. However, possible consequences of the cellular phone usage on human sperm parameters have not been investigated adequately. A total number of 27 males were enrolled in the study. The semen sample obtained from each participant was divided equally into two parts. One of the specimens was exposed to EMR emitted by an activated 900 MHz cellular phone, whereas the other was not. The concentration and motility of the specimens were compared to analyze the effects of EMR. Assessment of sperm movement in all specimens was performed using four criteria: (A) rapid progressive, (B) slow progressive, (C) nonprogressive, (D) no motility. Statistically significant changes were observed in the rapid progressive, slow progressive and no-motility categories of sperm movement. EMR exposure caused a subtle decrease in the rapid progressive and slow progressive sperm movement. It also caused an increase in the no-motility category of sperm movement. There was no statistically significant difference in the sperm concentration between two groups. These data suggest that EMR emitted by cellular phone influences human sperm motility. In addition to these acute adverse effects of EMR on sperm motility, long-term EMR exposure may lead to behavioral or structural changes of the male germ cell. These effects may be observed later in life, and they are to be investigated more seriously.

  15. IN VITRO CARDIAC CELLULAR AND MOLECULAR EFFECTS OF AIR POLLUTION PARTICLE CONSTITUENTS

    EPA Science Inventory

    In Vitro Cardiac Cellular and Molecular Effects of Air Pollution Particle Constituents
    Travis L. Knuckles1, Richard Jaskot2, Judy Richards2, and Kevin L. Dreher2. 1North Carolina State University, College of Veterinary Medicine, Raleigh, NC 27606, 2USEPA, Research Triangle Pa...

  16. Effectiveness of Conceptual Change Text-Oriented Instruction on Students' Understanding of Cellular Respiration Concepts

    ERIC Educational Resources Information Center

    Cakirt, Ozlem S.; Geban, Omer; Yuruk, Nejla

    2002-01-01

    This study investigated the effect of conceptual change text-oriented instruction over traditional instruction on students' understanding of cellular respiration concepts and their attitudes toward biology as a school subject. The sample of this study consisted of 84 eleventh-grade students from four classes of a high school. Two of the classes…

  17. MATERNAL FOLATE DEFICIENCY AMPLIFIES THE CELLULAR AND TERATOLOGIC EFFECTS OF TOMUDEX

    EPA Science Inventory

    Lau, C., J.E. Andrews, B.E. Grey*, R.G. Hanson*, J.R. Thibodeaux* and J.M. Rogers. Reproductive Toxicology Division, NHEERL, US EPA, ORD, Research Triangle Park, North Carolina. Maternal folate deficiency amplifies the cellular and teratologic effects of Tomudex.
    Maternal fo...

  18. Effectiveness of Conceptual Change Text Oriented Instruction on Students' Understanding of Cellular Respiration Concepts.

    ERIC Educational Resources Information Center

    Cakir, Ozlem S.; Yuruk, Nejla; Geban, Omer

    The purpose of the study is to compare the effectiveness of conceptual change text oriented instruction and traditional instruction on students' understanding of cellular respiration concepts and their attitudes toward biology as a school subject. The sample of this study consisted of 84 eleventh-grade students from the 4 classes of a high school.…

  19. Effect of heated naringenin on immunomodulatory properties and cellular antioxidant activity.

    PubMed

    Maatouk, Mouna; Elgueder, Dorra; Mustapha, Nadia; Chaaban, Hind; Bzéouich, Imen Mokdad; Loannou, Irina; Kilani, Soumaya; Ghoul, Mohamed; Ghedira, Kamel; Chekir-Ghedira, Leila

    2016-11-01

    Naringenin is one of the most popular flavonoids derived from citrus. It has been reported to be an effective anti-inflammatory compound. Citrus fruit may be used raw, cooked, stewed, or boiled. The present study was conducted to investigate the effect of thermal processes on naringenin in its immunomodulatory and cellular antioxidant activities. The effects of flavonoids on B and T cell proliferation were assessed on splenocytes stimulated or not with mitogens. However, their effects on cytotoxic T lymphocyte (CTL) and natural killer (NK) activities were assessed in splenocytes co-incubated with target cells. The amount of nitric oxide production and the lysosomal enzyme activity were evaluated in vitro on mouse peritoneal macrophages. Cellular antioxidant activity in splenocytes and macrophages was determined by measuring the fluorescence of the dichlorofluorescin (DCF). Our findings revealed that naringenin induces B cell proliferation and enhances NK activity. The highest concentration of native naringenin exhibits a significant proliferation of T cells, induces CTL activity, and inhibits cellular oxidation in macrophages. Conversely, it was observed that when heat-processed, naringenin improves the cellular antioxidant activity in splenocytes, increases the cytotoxic activity of NK cells, and suppresses the cytotoxicity of T cells. However, heat treatment maintains the anti-inflammatory potency of naringenin.

  20. Cellular uptake and metabolism of curcuminoids in monocytes/macrophages: regulatory effects on lipid accumulation

    USDA-ARS?s Scientific Manuscript database

    We previously showed that curcumin (CUR) may increase lipid accumulation in cultured THP-1 monocytes/macrophages, but tetrahydrocurcumin (THC), an in vivo metabolite of CUR, had no such effect. In the present study, we have hypothesized that different cellular uptake and/or metabolism of CUR and THC...

  1. High resolution time-course mapping of early transcriptomic, molecular and cellular phenotypes in Huntington's disease CAG knock-in mice across multiple genetic backgrounds.

    PubMed

    Ament, Seth A; Pearl, Jocelynn R; Grindeland, Andrea; St Claire, Jason; Earls, John C; Kovalenko, Marina; Gillis, Tammy; Mysore, Jayalakshmi; Gusella, James F; Lee, Jong-Min; Kwak, Seung; Howland, David; Lee, Min Young; Baxter, David; Scherler, Kelsey; Wang, Kai; Geman, Donald; Carroll, Jeffrey B; MacDonald, Marcy E; Carlson, George; Wheeler, Vanessa C; Price, Nathan D; Hood, Leroy E

    2017-03-01

    Huntington's disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in understanding the disease progression that leads from the HD mutation to massive cell death in the striatum is the ability to characterize the subtle and early functional consequences of the CAG expansion longitudinally. We used dense time course sampling between 4 and 20 postnatal weeks to characterize early transcriptomic, molecular and cellular phenotypes in the striatum of six distinct knock-in mouse models of the HD mutation. We studied the effects of the HttQ111 allele on the C57BL/6J, CD-1, FVB/NCr1, and 129S2/SvPasCrl genetic backgrounds, and of two additional alleles, HttQ92 and HttQ50, on the C57BL/6J background. We describe the emergence of a transcriptomic signature in HttQ111/+  mice involving hundreds of differentially expressed genes and changes in diverse molecular pathways. We also show that this time course spanned the onset of mutant huntingtin nuclear localization phenotypes and somatic CAG-length instability in the striatum. Genetic background strongly influenced the magnitude and age at onset of these effects. This work provides a foundation for understanding the earliest transcriptional and molecular changes contributing to HD pathogenesis. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Effect of crumb cellular structure characterized by image analysis on cake softness.

    PubMed

    Dewaest, Marine; Villemejane, Cindy; Berland, Sophie; Neron, Stéphane; Clement, Jérôme; Verel, Aliette; Michon, Camille

    2018-06-01

    Sponge cake is a cereal product characterized by an aerated crumb and appreciated for its softness. When formulating such product, it is interesting to be able to characterize the crumb structure using image analysis and to bring knowledge about the effects of the crumb cellular structure on its mechanical properties which contribute to softness. An image analysis method based on mathematical morphology was adapted from the one developed for bread crumb. In order to evaluate its ability to discriminate cellular structures, series of cakes were prepared using two rather similar emulsifiers but also using flours with different aging times before use. The mechanical properties of the crumbs of these different cakes were also characterized. It allowed a cell structure classification taking into account cell size and homogeneity, but also cell wall thickness and the number of holes in the walls. Interestingly, the cellular structure differences had a larger impact on the aerated crumb Young modulus than the wall firmness. Increasing the aging time of flour before use leads to the production of firmer crumbs due to coarser and inhomogeneous cellular structures. Changing the composition of the emulsifier may change the cellular structure and, depending on the type of the structural changes, have an impact on the firmness of the crumb. Cellular structure rather than cell wall firmness was found to impact cake crumb firmness. The new fast and automated tool for cake crumb structure analysis allows detecting quickly any change in cell size or homogeneity but also cell wall thickness and number of holes in the walls (openness degree). To obtain a softer crumb, it seems that options are to decrease the cell size and the cell wall thickness and/or to increase the openness degree. It is then possible to easily evaluate the effects of ingredients (flour composition, emulsifier …) or change in the process on the crumb structure and thus its softness. Moreover, this image

  3. The Effects of Early Language Enrichment

    ERIC Educational Resources Information Center

    Fowler, William; Ogston, Karen; Roberts, Gloria; Swenson, Amy

    2006-01-01

    Over two decades, six studies evaluated the effects of a home-based early language program on the development of 101 infants. Parents engaged in enrichment activities with their infants over a one-year period that began when the infants were between three and 13 months of age. Participants from families with varied levels of education were…

  4. Anti-oxidative cellular protection effect of fasting-induced autophagy as a mechanism for hormesis.

    PubMed

    Moore, Michael N; Shaw, Jennifer P; Ferrar Adams, Dawn R; Viarengo, Aldo

    2015-06-01

    The aim of this investigation was to test the hypothesis that fasting-induced augmented lysosomal autophagic turnover of cellular proteins and organelles will reduce potentially harmful lipofuscin (age-pigment) formation in cells by more effectively removing oxidatively damaged proteins. An animal model (marine snail--common periwinkle, Littorina littorea) was used to experimentally test this hypothesis. Snails were deprived of algal food for 7 days to induce an augmented autophagic response in their hepatopancreatic digestive cells (hepatocyte analogues). This treatment resulted in a 25% reduction in the cellular content of lipofuscin in the digestive cells of the fasting animals in comparison with snails fed ad libitum on green alga (Ulva lactuca). Similar findings have previously been observed in the digestive cells of marine mussels subjected to copper-induced oxidative stress. Additional measurements showed that fasting significantly increased cellular health based on lysosomal membrane stability, and reduced lipid peroxidation and lysosomal/cellular triglyceride. These findings support the hypothesis that fasting-induced augmented autophagic turnover of cellular proteins has an anti-oxidative cytoprotective effect by more effectively removing damaged proteins, resulting in a reduction in the formation of potentially harmful proteinaceous aggregates such as lipofuscin. The inference from this study is that autophagy is important in mediating hormesis. An increase was demonstrated in physiological complexity with fasting, using graph theory in a directed cell physiology network (digraph) model to integrate the various biomarkers. This was commensurate with increased health status, and supportive of the hormesis hypothesis. The potential role of enhanced autophagic lysosomal removal of damaged proteins in the evolutionary acquisition of stress tolerance in intertidal molluscs is discussed and parallels are drawn with the growing evidence for the involvement of

  5. [Evaluation of Cellular Effects Caused by Lunar Regolith Simulant Including Fine Particles].

    PubMed

    Horie, Masanori; Miki, Takeo; Honma, Yoshiyuki; Aoki, Shigeru; Morimoto, Yasuo

    2015-06-01

    The National Aeronautics and Space Administration has announced a plan to establish a manned colony on the surface of the moon, and our country, Japan, has declared its participation. The surface of the moon is covered with soil called lunar regolith, which includes fine particles. It is possible that humans will inhale lunar regolith if it is brought into the spaceship. Therefore, an evaluation of the pulmonary effects caused by lunar regolith is important for exploration of the moon. In the present study, we examine the cellular effects of lunar regolith simulant, whose components are similar to those of lunar regolith. We focused on the chemical component and particle size in particular. The regolith simulant was fractionated to < 10 μm, < 25 μm and 10-25 μm by gravitational sedimentation in suspensions. We also examined the cellular effects of fine regolith simulant whose primary particle size is 5.10 μm. These regolith simulants were applied to human lung carcinoma A549 cells at concentrations of 0.1 and 1.0 mg/ml. Cytotoxicity, oxidative stress and immune response were examined after 24 h exposure. Cell membrane damage, mitochondrial dysfunction and induction of Interleukin-8 (IL-8) were observed at the concentration of 1.0 mg/ml. The cellular effects of the regolith simulant at the concentration of 0.1 mg/ml were small, as compared with crystalline silica as a positive control. Secretion of IL-1β and tumor necrosis factor-α (TNF-α) was observed at the concentration of 1.0 mg/ml, but induction of gene expression was not observed at 24 h after exposure. Induction of cellular oxidative stress was small. Although the cellular effects tended to be stronger in the < 10 μm particles, there was no remarkable difference. These results suggest that the chemical components and particle size have little relationship to the cellular effects of lunar regolith simulant such as cell membrane damage, induction of oxidative stress and proinflammatory effect.

  6. Aspherical Supernovae: Effects on Early Light Curves

    NASA Astrophysics Data System (ADS)

    Afsariardchi, Niloufar; Matzner, Christopher D.

    2018-04-01

    Early light from core-collapse supernovae, now detectable in high-cadence surveys, holds clues to a star and its environment just before it explodes. However, effects that alter the early light have not been fully explored. We highlight the possibility of nonradial flows at the time of shock breakout. These develop in sufficiently nonspherical explosions if the progenitor is not too diffuse. When they do develop, nonradial flows limit ejecta speeds and cause ejecta–ejecta collisions. We explore these phenomena and their observational implications using global, axisymmetric, nonrelativistic FLASH simulations of simplified polytropic progenitors, which we scale to representative stars. We develop a method to track photon production within the ejecta, enabling us to estimate band-dependent light curves from adiabatic simulations. Immediate breakout emission becomes hidden as an oblique flow develops. Nonspherical effects lead the shock-heated ejecta to release a more constant luminosity at a higher, evolving color temperature at early times, effectively mixing breakout light with the early light curve. Collisions between nonradial ejecta thermalize a small fraction of the explosion energy; we will address emission from these collisions in a subsequent paper.

  7. [Effects of sub-micro emulsion composition on cellular disposition of incorporated lipophilic drug].

    PubMed

    Sun, Xiao-Yi; Xiang, Zhi-Qiang; Wu, Shuo; Lv, Yuan-Yuan; Liang, Wen-Quan

    2013-09-01

    To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug. Sub-micro emulsions containing 10 % oil, 1.2 % lecithin and 2.25 % glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated. Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09 ± 1.98)ng/μg protein which had significant difference with control group [(38.54 ± 0.34)ng/μg protein]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73 ± 0.84)ng/μg protein, which was about 3 times of that in anionic emulsions [(15.71 ± 0.74)ng/μg protein], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug. Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination.

  8. Effects of sodium fluoride on blood cellular and humoral immunity in mice.

    PubMed

    Guo, Hongrui; Kuang, Ping; Luo, Qin; Cui, Hengmin; Deng, Huidan; Liu, Huan; Lu, Yujiao; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Li, Yinglun; Wang, Xun; Zhao, Ling

    2017-10-17

    Exposure to high fluorine can cause toxicity in human and animals. Currently, there are no systematic studies on effects of high fluorine on blood cellular immunity and humoral immunity in mice. We evaluated the alterations of blood cellular immunity and humoral immunity in mice by using flow cytometry and ELISA. In the cellular immunity, we found that sodium fluoride (NaF) in excess of 12 mg/Kg resulted in a significant decrease in the percentages of CD3 + , CD3 + CD4 + , CD3 + CD8 + T lymphocytes in the peripheral blood. Meanwhile, serum T helper type 1 (Th1) cytokines including interleukin (IL)-2, interferon (IFN)-γ, tumor necrosis factor (TNF), and Th2 cytokines including IL-4, IL-6, IL-10, and Th17 cytokine (IL-17A) contents were decreased. In the humoral immunity, NaF reduced the peripheral blood percentages of CD19 + B lymphocytes and serum immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM). The above results show that NaF can reduce blood cellular and humoral immune function in mice, providing an excellent animal model for clinical studies on immunotoxicity-related fluorosis.

  9. Inhibitory effects of OK-432 (Picibanil) on cellular proliferation and adhesive capacity of breast carcinoma cells.

    PubMed

    Horii, Yoshio; Iino, Yuichi; Maemura, Michio; Horiguchi, Jun; Morishita, Yasuo

    2005-02-01

    We investigated the potent inhibitory effects of OK-432 (Picibanil) on both cellular adhesion and cell proliferation of estrogen-dependent (MCF-7) or estrogen-independent (MDA-MB-231) breast carcinoma cells. Cellular proliferation of both MCF-7 and MDA-MB-231 cells was markedly inhibited in a dose-dependent manner, when the carcinoma cells were exposed to OK-432. Cell attachment assay demonstrated that incubation with OK-432 for 24 h reduced integrin-mediated cellular adhesion of both cell types. However, fluorescence activated cell sorter (FACS) analysis revealed that incubation with OK-432 for 24 h did not decrease the cell surface expressions of any integrins. These results suggest that the binding avidity of integrins is reduced by OK-432 without alteration of the integrin expression. We conclude that OK-432 inhibits integrin-mediated cellular adhesion as well as cell proliferation of breast carcinoma cells regardless of estrogen-dependence, and that these actions of OK-432 contribute to prevention or inhibition of breast carcinoma invasion and metastasis.

  10. Cellular Antioxidant Effect of Four Bromophenols from the Red Algae, Vertebrata lanosa

    PubMed Central

    Olsen, Elisabeth K.; Hansen, Espen; Isaksson, Johan; Andersen, Jeanette H.

    2013-01-01

    Three known bromophenols, 2,3-dibromo-4,5-dihydroxybenzylaldehyde (1), 2,2′,3-tribromo-3′,4,4′,5-tetrahydroxy-6′-hydroxymethyldiphenylmethane (2) and bis(2,3-dibromo-4,5-dihydroxylbenzyl) ether (3), and one new one, 5,5″-oxybis(methylene)bis(3-bromo-4-(2′,3′-dibromo-4′,5′-dihydroxylbenzyl)benzene-1,2-diol) (4), were isolated from an extract of the red alga, Vertebrata lanosa. The antioxidant activity of these four bromophenols was examined using one biochemical and two cellular assays: Oxygen Radical Absorbance Capacity (ORAC), Cellular Antioxidant Activity (CAA) and Cellular Lipid Peroxidation Antioxidant Activity (CLPAA) assays. Compound 2 distinguished itself by showing potent activity, having a better antioxidant effect than luteolin in both the CAA and CLPAA assays and of quercetin in the CLPAA assay. Although several bromophenols are known to be potent antioxidants in biochemical assays, this is the first time their cellular antioxidant activity has been demonstrated. PMID:23921722

  11. A priming dose of protons alters the early cardiac cellular and molecular response to 56Fe irradiation

    NASA Astrophysics Data System (ADS)

    Ramadan, Samy S.; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R.; Hauer-Jensen, Martin; Nelson, Gregory A.; Boerma, Marjan

    2016-02-01

    Purpose: Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a ;priming; dose of protons on the cardiac cellular and molecular response to a ;challenge; dose of 56Fe in a mouse model. Methods: Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of 56Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of 56Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Results: Exposure to 56Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before 56Fe prevented all of the responses to 56Fe. Conclusions: This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions.

  12. A priming dose of protons alters the early cardiac cellular and molecular response to (56)Fe irradiation.

    PubMed

    Ramadan, Samy S; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R; Hauer-Jensen, Martin; Nelson, Gregory A; Boerma, Marjan

    2016-02-01

    Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a "priming" dose of protons on the cardiac cellular and molecular response to a "challenge" dose of (56)Fe in a mouse model. Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of (56)Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of (56)Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Exposure to (56)Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before (56)Fe prevented all of the responses to (56)Fe. This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

  13. A priming dose of protons alters the early cardiac cellular and molecular response to 56Fe irradiation

    PubMed Central

    Ramadan, Samy S.; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R.; Hauer-Jensen, Martin; Nelson, Gregory A.; Boerma, Marjan

    2015-01-01

    Purpose Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a “priming” dose of protons on the cardiac cellular and molecular response to a “challenge” dose of 56Fe in a mouse model. Methods Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of 56Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of 56Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Results Exposure to 56Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before 56Fe prevented all of the responses to 56Fe. Conclusions This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions. PMID:26948008

  14. New approach to modulate retinal cellular toxic effects of high glucose using marine epa and dha.

    PubMed

    Dutot, Mélody; de la Tourrette, Violaine; Fagon, Roxane; Rat, Patrice

    2011-06-16

    Protective effects of omega-3 fatty acids against cellular damages of high glucose were studied on retinal pigmented epithelial (RPE) cells. Retinal epithelial cells were incubated with omega-3 marine oils rich in EPA and DHA and then with high glucose (25 mM) for 48 hours. Cellular responses were compared to normal glucose (5 mM): intracellular redox status, reactive oxygen species (ROS), mitochondrial succinate deshydrogenase activity, inflammatory cytokines release and caveolin-1 expression were evaluated using microplate cytometry, ELISA and flow cytometry techniques. Fatty acids incorporation in retinal cell membranes was analysed using chromatography. Preincubation of the cells with fish oil decreased ROS overproduction, mitochondrial alterations and TNFα release. These protective effects could be attributed to an increase in caveolin-1 expression induced by marine oil. Marine formulations rich in omega-3 fatty acids represent a promising therapeutic approach for diabetic retinopathy.

  15. Generation of anti-porcine CD69 monoclonal antibodies and their usefulness to evaluate early activation of cellular immunity by flow cytometric analysis.

    PubMed

    Hayashi, Yumiko; Okutani, Mie; Ogawa, Shohei; Tsukahara, Takamitsu; Inoue, Ryo

    2018-05-01

    T cell-mediated cellular immunity and humoral immunity are equally important for the prevention of diseases. To assess activation of human and mouse cellular immunity, early activation markers of lymphocytes are often used in flow cytometry targeting expression of CD69 molecules. Response of humoral immunity against infection or vaccination has been well investigated in pigs, but that of cellular immunity has been largely neglected due to lack of direct evaluation tools. Thus, in pig research a proper assay of antibody reacted with porcine CD69 is still unavailable. In the present study, two anti-porcine CD69 mAb-producing mouse hybridomas, 01-14-22-51 (IgG2b-κ) and 01-22-44-102 (IgG2a-κ), both showing fine reactivity with phorbol 12-myristate 13-acetate (PMA) and ionomycin-stimulated porcine peripheral blood lymphocytes in flow cytometry, were established. When porcine peripheral blood lymphocytes were activated with PMA and ionomycin and analyzed by flow cytometry, it was found that both mAbs generated in this study stained about 70% of lymphocytes. In contrast, after an identical procedure, only 5% and 13.5% of lymphocytes were stained with anti-interferon-γ mAb and anti-tumor necrosis factor-α mAb, respectively. These results indicate that evaluation of cellular immunity activation turns more sensitive after using our newly generated mAbs. © 2018 Japanese Society of Animal Science.

  16. [In vitro study over statins effects on cellular growth curves and its reversibility with mevalonate].

    PubMed

    Millan Núñez-Cortés, Jesús; Alvarez Rodriguez, Ysmael; Alvarez Novés, Granada; Recarte Garcia-Andrade, Carlos; Alvarez-Sala Walther, Luis

    2014-01-01

    HMG-CoA-Reductase inhibitors, also known as statins, are currently the most powerful cholesterol-lowering drugs available on the market. Clinical trials and experimental evidence suggest that statins have heavy anti-atherosclerotic effects. These are in part consequence of lipid lowering but also result from pleiotropic actions of the drugs. These so-called pleiotropic properties affect various aspects of cell function, inflammation, coagulation, and vasomotor activity. These effects are mediated either indirectly through LDL-c reduction or via a direct effect on cellular functions. Although many of the pleiotropic properties of statins may be a class effect, some may be unique to certain agents and account for differences in their pharmacological activity. So, although statins typically have similar effects on LDL-c levels, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects. In this paper we analize the in vitro effects of different statins over different cell lines from cells implicated in atherosclerotic process: endothelial cells, fibroblasts, and vascular muscular cells. In relation with our results we can proof that the effects of different dosis of different statins provides singular effects over growth curves of different cellular lines, a despite of a class-dependent effects. So, pleiotropic effects and its reversibility with mevalonate are different according with the molecule and the dosis. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

  17. Effect of arginine methylation on the RNA recognition and cellular uptake of Tat-derived peptides.

    PubMed

    Li, Jhe-Hao; Chiu, Wen-Chieh; Yao, Yun-Chiao; Cheng, Richard P

    2015-05-01

    Arginine (Arg) methylation is a common post-translational modification that regulates gene expression and viral infection. The HIV-1 Tat protein is an essential regulatory protein for HIV proliferation, and is methylated in the cell. The basic region (residues 47-57) of the Tat protein contains six Arg residues, and is responsible for two biological functions: RNA recognition and cellular uptake. In this study, we explore the effect of three different methylation states at each Arg residue in Tat-derived peptides on the two biological functions. The Tat-derived peptides were synthesized by solid phase peptide synthesis. TAR RNA binding of the peptides was assessed by electrophoresis mobility shift assays. The cellular uptake of the peptides into Jurkat cells was determined by flow cytometry. Our results showed that RNA recognition was affected by both methylation state and position. In particular, asymmetric dimethylation at position 53 decreased TAR RNA binding affinity significantly, but unexpectedly less so upon asymmetric dimethylation at position 52. The RNA binding affinity even slightly increased upon methylation at some of the flanking Arg residues. Upon Arg methylation, the cellular uptake of Tat-derived peptides mostly decreased. Interestingly, cellular uptake of Tat-derived peptides with a single asymmetrically dimethylated Arg residue was similar to the native all Arg peptide (at 120 μM). Based on our results, TAR RNA binding apparently required both guanidinium terminal NH groups on Arg53, whereas cellular uptake apparently required guanidinium terminal NH₂ groups instead. These results should provide insight into how nature uses arginine methylation to regulate different biological functions, and should be useful for the development of functional molecules with methylated arginines. Copyright © 2015. Published by Elsevier Ltd.

  18. Enhanced Medial Collateral Ligament Healing using Mesenchymal Stem Cells: Dosage Effects on Cellular Response and Cytokine Profile

    PubMed Central

    Saether, Erin E.; Chamberlain, Connie S.; Leiferman, Ellen M.; Kondratko-Mittnacht, Jaclyn R.; Li, Wan Ju; Brickson, Stacey L.; Vanderby, Ray

    2013-01-01

    Mesenchymal stem cells (MSCs) have potential therapeutic applications for musculoskeletal injuries due to their ability to differentiate into several tissue cell types and modulate immune and inflammatory responses. These immune-modulatory properties were examined in vivo during early stage rat medial collateral ligament healing. Two different cell doses (low dose 1×106 or high dose 4×106 MSCs) were administered at the time of injury and compared with normal ligament healing at days 5 and 14 post-injury. At both times, the high dose MSC group demonstrated a significant decrease in M2 macrophages compared to controls. At day 14, fewer M1 macrophages were detected in the low dose group compared to the high dose group. These results, along with significant changes in procollagen I, proliferating cells, and endothelialization suggest that MSCs can alter the cellular response during healing in a dose-dependent manner. The higher dose ligaments also had increased expression of several pro-inflammatory cytokines at day 5 (IL-1β, IFNγ, IL-2) and increased expression of IL-12 at day 14. Mechanical testing at day 14 revealed increased failure strength and stiffness in low dose ligaments compared to controls. Based on these improved mechanical properties, MSCs enhanced functional healing when applied at a lower dose. Different doses of MSCs uniquely affected the cellular response and cytokine expression in healing ligaments. Interestingly, the lower dose of cells proved to be most effective in improving functional properties. PMID:24174129

  19. Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity.

    PubMed

    Topdag, M; Iseri, M; Gelenli, E; Yardimoglu, M; Yazir, Y; Ulubil, S A; Topdag, D O; Ustundag, E

    2012-11-01

    This study aimed to contribute to the literature on the prevention and treatment of ototoxicity due to various drugs and chemicals. This study compared the histological effects of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity, in 36 rats. Dexamethasone and memantine had significant effects on the stria vascularis, organ of Corti and spiral ganglion (p < 0.05). Although piracetam decreased the apoptosis rate, this effect was not statistically significant (p > 0.05). Dexamethasone and memantine were found superior to piracetam in reducing apoptosis due to cisplatin ototoxicity. Further studies of this subject are needed, incorporating electron microscopy and auditory brainstem response testing.

  20. Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B

    PubMed Central

    Wang, Ke-Xia; Zhang, Li-Hua; Peng, Jiang-Long; Liang, Yong; Wang, Xue-Feng; Zhi, Hui; Wang, Xiang-Xia; Geng, Huan-Xiong

    2005-01-01

    AIM: To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. METHODS: The levels of T lymphocyte subsets and mIL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole. RESULTS: After one course of treatment with liniment levamisole, the levels of CD3+, CD4+, and the ratio of CD4+/CD8+ increased as compared to those before the treatment but the level of CD8+ decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole. CONCLUSION: Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B. PMID:16437674

  1. Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B.

    PubMed

    Wang, Ke-Xia; Zhang, Li-Hua; Peng, Jiang-Long; Liang, Yong; Wang, Xue-Feng; Zhi, Hui; Wang, Xiang-Xia; Geng, Huan-Xiong

    2005-12-07

    To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. The levels of T lymphocyte subsets and mIL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole. After one course of treatment with liniment levamisole, the levels of CD3(+), CD4(+), and the ratio of CD4(+)/CD8(+) increased as compared to those before the treatment but the level of CD8(+) decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole. Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B.

  2. EFFECT OF X-IRRADIATION ON THE CELLULAR AND HUMORAL RESPONSES TO ANTIGEN

    SciTech Connect

    Speirs, R.S.

    1962-01-01

    Mice were immunized by 6 subcutaneous injections of tetanus toxoid before exposure to 500 r x radiation. At various times after irradiation the animals were challenged with intraperitoneal injections of tetanus toxoid and serum antibody titers were determined. Results indicate that the time of irradiation in relation to antigen injection greatly influences the cellular response as well as antibody production. High radiation doses prior to antigen injection reduce the number of cells capable of responding and also inhibit the production of antibody. As the animals recovered from the effects of irradiation the production of antibody appeared to reflect the capacitymore » of the eosinophils to respond. It was concluded that eosinophils play an intermediate role in the cellular everts that lead to the production of antibody. (C.H.)« less

  3. The effects of early life adversity on the immune system.

    PubMed

    Elwenspoek, Martha M C; Kuehn, Annette; Muller, Claude P; Turner, Jonathan D

    2017-08-01

    Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences. We describe the current understanding of the 'ELA immune phenotype', characterized by inflammation, impairment of the cellular immune system, and immunosenescence. However, at present, data addressing specific immune functions are limited and there is a need for high-quality, well powered, longitudinal studies to unravel cause from effect. Besides the immune system, also the stress system and health behaviors are altered in ELA. We discuss probable underlying mechanisms based on epigenetic programming that could explain the ELA immune phenotype and whether this is a direct effect of immune programming or an indirect consequence of changes in behavior or stress reactivity. Understanding the underlying mechanisms will help define effective strategies to prevent or counteract negative ELA-associated outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Effects of cellular origin on differentiation of human induced pluripotent stem cell–derived endothelial cells

    PubMed Central

    Zhao, Ming-Tao; Jahanbani, Fereshteh; Lee, Won Hee; Snyder, Michael P.

    2016-01-01

    Human induced pluripotent stem cells (iPSCs) can be derived from various types of somatic cells by transient overexpression of 4 Yamanaka factors (OCT4, SOX2, C-MYC, and KLF4). Patient-specific iPSC derivatives (e.g., neuronal, cardiac, hepatic, muscular, and endothelial cells [ECs]) hold great promise in drug discovery and regenerative medicine. In this study, we aimed to evaluate whether the cellular origin can affect the differentiation, in vivo behavior, and single-cell gene expression signatures of human iPSC–derived ECs. We derived human iPSCs from 3 types of somatic cells of the same individuals: fibroblasts (FB-iPSCs), ECs (EC-iPSCs), and cardiac progenitor cells (CPC-iPSCs). We then differentiated them into ECs by sequential administration of Activin, BMP4, bFGF, and VEGF. EC-iPSCs at early passage (10 < P < 20) showed higher EC differentiation propensity and gene expression of EC-specific markers (PECAM1 and NOS3) than FB-iPSCs and CPC-iPSCs. In vivo transplanted EC-iPSC–ECs were recovered with a higher percentage of CD31+ population and expressed higher EC-specific gene expression markers (PECAM1, KDR, and ICAM) as revealed by microfluidic single-cell quantitative PCR (qPCR). In vitro EC-iPSC–ECs maintained a higher CD31+ population than FB-iPSC–ECs and CPC-iPSC–ECs with long-term culturing and passaging. These results indicate that cellular origin may influence lineage differentiation propensity of human iPSCs; hence, the somatic memory carried by early passage iPSCs should be carefully considered before clinical translation. PMID:27398408

  5. Early and late arrhythmogenic effects of doxorubicin.

    PubMed

    Kilickap, Saadettin; Barista, Ibrahim; Akgul, Ebru; Aytemir, Kudret; Aksoy, Sercan; Tekuzman, Gulten

    2007-03-01

    To determine the incidence of early and late arrhythmogenic effects of doxorubicin-containing chemotherapy regimens. A prospective study including 29 patients who were treated with doxorubicin-containing regimens. Cardiac evaluation was based on 24-hour electrocardiographic monitorization (Holter), which was performed during the first cycle of doxorubicin-containing regimens, as well as after the last cycle of chemotherapy. The mean age of the patients was 45.8 +/- 15.1 (range 18-69). Holter records obtained during the first cycle of treatment revealed varying arrhythmias in 19 patients (65.5%) and in 18 (62.1%) patients after completion of therapy. One patient presented with syncope and both Mobitz Type 2 atrioventricular block and complete atrioventricular block were demonstrated. The patient subsequently underwent permanent pacemaker implantation. Doxorubicin may result in arrhythmias both in early and late periods of treatment. These arrhythmias are rarely life threatening.

  6. A study for bank effect on ship traffic in narrow water channels using cellular automata

    NASA Astrophysics Data System (ADS)

    Sun, Zhuo; Cong, Shuang; Pan, Junnan; Zheng, Jianfeng

    2017-12-01

    In narrow water channels, bank might affect nearby ships due to hydrodynamic forces (bank effect). To avoid accidents, different sailing rules (i.e., lane-changing, speed control) are required. In this paper, a two-lane cellular automata model is proposed to evaluate such phenomena. Numerical experiments show that ships will form a “slow-moving chunk” in the bank area, which will significantly block the flux. As further study demonstrated to alleviate bank effect, ship speed and bank length should be controlled.

  7. Cellular burdens and biological effects on tissue level caused by inhaled radon progenies.

    PubMed

    Madas, B G; Balásházy, I; Farkas, Á; Szoke, I

    2011-02-01

    In the case of radon exposure, the spatial distribution of deposited radioactive particles is highly inhomogeneous in the central airways. The object of this research is to investigate the consequences of this heterogeneity regarding cellular burdens in the bronchial epithelium and to study the possible biological effects at tissue level. Applying computational fluid and particle dynamics techniques, the deposition distribution of inhaled radon daughters has been determined in a bronchial airway model for 23 min of work in the New Mexico uranium mine corresponding to 0.0129 WLM exposure. A numerical epithelium model based on experimental data has been utilised in order to quantify cellular hits and doses. Finally, a carcinogenesis model considering cell death-induced cell-cycle shortening has been applied to assess the biological responses. Present computations reveal that cellular dose may reach 1.5 Gy, which is several orders of magnitude higher than tissue dose. The results are in agreement with the histological finding that the uneven deposition distribution of radon progenies may lead to inhomogeneous spatial distribution of tumours in the bronchial airways. In addition, at the macroscopic level, the relationship between cancer risk and radiation burden seems to be non-linear.

  8. Protein Corona Analysis of Silver Nanoparticles Links to Their Cellular Effects.

    PubMed

    Juling, Sabine; Niedzwiecka, Alicia; Böhmert, Linda; Lichtenstein, Dajana; Selve, Sören; Braeuning, Albert; Thünemann, Andreas F; Krause, Eberhard; Lampen, Alfonso

    2017-11-03

    The breadth of applications of nanoparticles and the access to food-associated consumer products containing nanosized materials lead to oral human exposure to such particles. In biological fluids nanoparticles dynamically interact with biomolecules and form a protein corona. Knowledge about the protein corona is of great interest for understanding the molecular effects of particles as well as their fate inside the human body. We used a mass spectrometry-based toxicoproteomics approach to elucidate mechanisms of toxicity of silver nanoparticles and to comprehensively characterize the protein corona formed around silver nanoparticles in Caco-2 human intestinal epithelial cells. Results were compared with respect to the cellular function of proteins either affected by exposure to nanoparticles or present in the protein corona. A transcriptomic data set was included in the analyses in order to obtain a combined multiomics view of nanoparticle-affected cellular processes. A relationship between corona proteins and the proteomic or transcriptomic responses was revealed, showing that differentially regulated proteins or transcripts were engaged in the same cellular signaling pathways. Protein corona analyses of nanoparticles in cells might therefore help in obtaining information about the molecular consequences of nanoparticle treatment.

  9. The Cellular and Molecular Carcinogenic Effects of Radon Exposure: A Review

    PubMed Central

    Robertson, Aaron; Allen, James; Laney, Robin; Curnow, Alison

    2013-01-01

    Radon-222 is a naturally occurring radioactive gas that is responsible for approximately half of the human annual background radiation exposure globally. Chronic exposure to radon and its decay products is estimated to be the second leading cause of lung cancer behind smoking, and links to other forms of neoplasms have been postulated. Ionizing radiation emitted during the radioactive decay of radon and its progeny can induce a variety of cytogenetic effects that can be biologically damaging and result in an increased risk of carcinogenesis. Suggested effects produced as a result of alpha particle exposure from radon include mutations, chromosome aberrations, generation of reactive oxygen species, modification of the cell cycle, up or down regulation of cytokines and the increased production of proteins associated with cell-cycle regulation and carcinogenesis. A number of potential biomarkers of exposure, including translocations at codon 249 of TP53 in addition to HPRT mutations, have been suggested although, in conclusion, the evidence for such hotspots is insufficient. There is also substantial evidence of bystander effects, which may provide complications when calculating risk estimates as a result of exposure, particularly at low doses where cellular responses often appear to deviate from the linear, no-threshold hypothesis. At low doses, effects may also be dependent on cellular conditions as opposed to dose. The cellular and molecular carcinogenic effects of radon exposure have been observed to be both numerous and complex and the elevated chronic exposure of man may therefore pose a significant public health risk that may extend beyond the association with lung carcinogenesis. PMID:23880854

  10. Effects of vitamin E supplementation on cellular α-tocopherol concentrations of neutrophils in Holstein calves

    PubMed Central

    Higuchi, Hidetoshi; Ito, Erina; Iwano, Hidetoma; Oikawa, Shin; Nagahata, Hajime

    2013-01-01

    The effects of vitamin E supplementation on cellular α-tocopherol concentrations of neutrophils from Holstein calves and the mechanism of scavenger receptor class B type I (SR-BI)-mediated uptake of α-tocopherol were examined. Cellular α-tocopherol concentrations in vitamin E-treated calves increased from 3.5 ± 0.38 to 7.2 ± 0.84 μg/107 cells, respectively, within 14 d after vitamin E supplementation; these concentrations were significantly higher than those of control calves (P < 0.01). The expression indices of SR-BI [a major receptor that recognizes high-density lipoprotein (HDL)] mRNA in neutrophils were two to five times higher (P < 0.01) in neutrophils obtained from vitamin E-supplemented calves compared with those from control calves, and anti-SR-B1 antibody, ranging from 0.1 to 1.0 μg/mL, significantly (P < 0.01) decreased cellular α-tocopherol concentrations of neutrophils. Cytochalasin D and latrunculin B, major inhibitors of actin polymerization of neutrophils, significantly decreased cellular α-tocopherol concentrations of neutrophils (P < 0.01). Our results demonstrated that in vitamin E-supplemented calves: 1) α-tocopherol is mainly distributed with HDL, 2) α-tocopherol within HDL is recognized by SR-BI on the surface of neutrophils, and 3) rearrangement of the actin cytoskeleton is a crucial step for the uptake of α-tocopherol by neutrophils. PMID:24082403

  11. Association between problematic cellular phone use and suicide: the moderating effect of family function and depression.

    PubMed

    Wang, Peng-Wei; Liu, Tai-Ling; Ko, Chih-Hung; Lin, Huang-Chi; Huang, Mei-Feng; Yeh, Yi-Chun; Yen, Cheng-Fang

    2014-02-01

    Suicidal ideation and attempt among adolescents are risk factors for eventual completed suicide. Cellular phone use (CPU) has markedly changed the everyday lives of adolescents. Issues about how cellular phone use relates to adolescent mental health, such as suicidal ideation and attempts, are important because of the high rate of cellular phone usage among children in that age group. This study explored the association between problematic CPU and suicidal ideation and attempts among adolescents and investigated how family function and depression influence the association between problematic CPU and suicidal ideation and attempts. A total of 5051 (2872 girls and 2179 boys) adolescents who owned at least one cellular phone completed the research questionnaires. We collected data on participants' CPU and suicidal behavior (ideation and attempts) during the past month as well as information on family function and history of depression. Five hundred thirty-two adolescents (10.54%) had problematic CPU. The rates of suicidal ideation were 23.50% and 11.76% in adolescents with problematic CPU and without problematic CPU, respectively. The rates of suicidal attempts in both groups were 13.70% and 5.45%, respectively. Family function, but not depression, had a moderating effect on the association between problematic CPU and suicidal ideation and attempt. This study highlights the association between problematic CPU and suicidal ideation as well as attempts and indicates that good family function may have a more significant role on reducing the risks of suicidal ideation and attempts in adolescents with problematic CPU than in those without problematic CPU. © 2014.

  12. δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.

    PubMed

    Chen, Jayson X; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S

    2017-01-01

    Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T), and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T, and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 wk. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. δ- and γ-Tocopherols Inhibit PhIP/DSS-induced Colon Carcinogenesis by Protection against Early Cellular and DNA Damages

    PubMed Central

    Chen, Jayson X.; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S.

    2017-01-01

    Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T) and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 weeks. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. PMID:27175800

  14. STAT3 and importins are novel mediators of early molecular and cellular responses in experimental duodenal ulceration.

    PubMed

    Khomenko, Tetyana; Deng, Xiaoming; Ahluwalia, Amrita; Tarnawski, Andrzej; Patel, Khushin N; Sandor, Zsuzsanna; Szabo, Sandor

    2014-02-01

    Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that directly upregulates VEGF, Ref-1, p21, and anti-apoptotic genes such as Bcl-xL. In this study, we hypothesized that STAT3 signaling is activated and provides a critical protective role that is required for enterocyte survival during the early phases of cysteamine-induced duodenal ulcers. We studied the effect of inhibition of STAT3 activity on cysteamine-induced duodenal ulcers in rats and egr-1 knockout mice using STAT3/DNA binding assay, immunohistochemistry, immunoblot, and quantitative reverse transcriptase PCR analyses. We found that G-quartet oligodeoxynucleotides T40214, a specific inhibitor of STAT3/DNA binding, aggravated cysteamine-induced duodenal ulcers in rats 2.8-fold (p < 0.05). In the pre-ulcerogenic stage, cysteamine induced STAT3 tyrosine phosphorylation, its translocation to nuclei, an increased expression and nuclear translocation of importin α and β in the rat duodenal mucosa. Cysteamine enhanced the binding of STAT3 to its DNA consensus sequences at 6, 12, and 24 h after cysteamine by 1.5-, 1.8-, and 3.5-fold, respectively, and activated the expression of STAT3 target genes such as VEGF, Bcl-xL, Ref-1, and STAT3-induced feedback inhibitor, a suppressor of cytokine signaling 3. We also demonstrated that egr-1 knockout mice, which are more susceptible to cysteamine-induced duodenal ulcers, had lower levels of STAT3 expression, its phosphorylation, expression of importin α or β, and STAT3/DNA binding than wild-type mice in response to cysteamine. Thus, STAT3 represents an important new molecular mechanism in experimental duodenal ulceration.

  15. Mathematical Modeling of Early Cellular Innate and Adaptive Immune Responses to Ischemia/Reperfusion Injury and Solid Organ Allotransplantation

    PubMed Central

    Day, Judy D.; Metes, Diana M.; Vodovotz, Yoram

    2015-01-01

    A mathematical model of the early inflammatory response in transplantation is formulated with ordinary differential equations. We first consider the inflammatory events associated only with the initial surgical procedure and the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft. These events release damage-associated molecular pattern molecules (DAMPs), thereby initiating an acute inflammatory response. In simulations of this model, resolution of inflammation depends on the severity of the tissue damage caused by these events and the patient’s (co)-morbidities. We augment a portion of a previously published mathematical model of acute inflammation with the inflammatory effects of T cells in the absence of antigenic allograft mismatch (but with DAMP release proportional to the degree of graft damage prior to transplant). Finally, we include the antigenic mismatch of the graft, which leads to the stimulation of potent memory T cell responses, leading to further DAMP release from the graft and concomitant increase in allograft damage. Regulatory mechanisms are also included at the final stage. Our simulations suggest that surgical injury and I/R-induced graft damage can be well-tolerated by the recipient when each is present alone, but that their combination (along with antigenic mismatch) may lead to acute rejection, as seen clinically in a subset of patients. An emergent phenomenon from our simulations is that low-level DAMP release can tolerize the recipient to a mismatched allograft, whereas different restimulation regimens resulted in an exaggerated rejection response, in agreement with published studies. We suggest that mechanistic mathematical models might serve as an adjunct for patient- or sub-group-specific predictions, simulated clinical studies, and rational design of immunosuppression. PMID:26441988

  16. Effects of resveratrol, oxyresveratrol, and their acetylated derivatives on cellular melanogenesis.

    PubMed

    Park, Jiaa; Park, Joon Heum; Suh, Hwa-Jin; Lee, In Chul; Koh, Jaesook; Boo, Yong Chool

    2014-07-01

    Resveratrol and oxyresveratrol are naturally occurring phenolic compounds with various bioactivities, but their uses in cosmetics have been partly limited by their chemical instabilities. This study was performed to examine the anti-melanogenic effects of the acetylated derivatives from resveratrol and oxyresveratrol. Resveratrol and oxyresveratrol were chemically modified to triacetyl resveratrol and tetraacetyl oxyresveratrol, respectively. The acetylated compounds were less susceptible than the parent compounds to oxidative discoloration. The acetylated compounds inhibited the activities of tyrosinases less than parent compounds in vitro, but they were as effective at cellular melanogenesis inhibition, indicating bioconversion to parent compounds inside cells. Supporting this notion, the parent compounds were regenerated when the acetylated compounds were digested with cell lysates. Although resveratrol and triacetyl resveratrol inhibited tyrosinase activity less effectively than oxyresveratrol and tetraacetyl oxyresveratrol in vitro, they inhibited cellular melanogenesis more effectively. This discrepancy was explained by strong inhibition of tyrosinase expression by resveratrol and triacetyl resveratrol. Experiments using a reconstituted skin model indicated that resveratrol derivatives can affect melanin synthesis and cell viability to different extents. Collectively, this study suggests that acetylated derivatives of resveratrol have great potential as anti-melanogenic agents for cosmetic use in terms of efficacy, safety, and stability.

  17. Study of effects of radio-wave frequency radiation emitted from cellular telephones on embryonic development of danio rerio

    NASA Astrophysics Data System (ADS)

    Vagula, Mary; Harkless, Ryan

    2013-05-01

    Radio wave frequency (RF) radiation emitted from cellular telephones has become increasingly ubiquitous as a result of the popularity of these phones. With the increasing and unavoidable exposure to RF radiation a reality, it is imperative that the effects of such radiation on living tissue be well understood. In particular, it is critical to understand any effects that RF radiation may have as a carcinogen and on embryonic development, as pregnant women are not exempt from such exposure. As a model organism, zebrafish (Danio rerio) have been studied extensively, and their value in studies of gene expression cannot be overstated. This study observed the effects of RF radiation on the embryonic development of zebrafish. The expression of two genes, shha and hoxb9a, that are key to the early development of the fish was examined. Both genes have homologs in humans as well as in other model organisms. Preliminary results suggest that exposure to cell phone radiation might have an effect on the expression of shha in zebrafish embryos, causing under expression. More trials are necessary to validate these results.

  18. On the effect of quantum noise in a quantum prisoner's dilemma cellular automaton

    NASA Astrophysics Data System (ADS)

    Alonso-Sanz, Ramón

    2017-06-01

    The disrupting effect of quantum noise on the dynamics of a spatial quantum formulation of the iterated prisoner's dilemma game with variable entangling is studied in this work. The game is played in the cellular automata manner, i.e., with local and synchronous interaction. It is concluded in this article that quantum noise induces in fair games the need for higher entanglement in order to make possible the emergence of the strategy pair ( Q, Q), which produces the same payoff of mutual cooperation. In unfair quantum versus classic player games, quantum noise delays the prevalence of the quantum player.

  19. Cellular effects of olomoucine, an inhibitor of cyclin-dependent kinases.

    PubMed

    Abraham, R T; Acquarone, M; Andersen, A; Asensi, A; Bellé, R; Berger, F; Bergounioux, C; Brunn, G; Buquet-Fagot, C; Fagot, D

    1995-01-01

    Olomoucine (2-(2-hydroxyethylamino)-6-benzylamino-9-methylpurine) has been recently described as a competitive inhibitor (ATP-binding site) of the cell cycle regulating p34cdc2/cyclin B, p33cdk2/cyclin A and p33cdk2/cyclin E kinases, the brain p33cdk5/p35 kinase and the ERK1/MAP-kinase. The unusual specificity of this compound towards cell cycle regulating enzymes suggests that it could inhibit certain steps of the cell cycle. The cellular effects of olomoucine were investigated in a large variety of plant and animal models. This compound inhibits the G1/S transition of unicellular algae (dinoflagellate and diatom). It blocks Fucus zygote cleavage and development of Laminaria gametophytes. Stimulated Petunia mesophyl protoplasts are arrested in G1 by olomoucine. By arresting cleavage it blocks the Laminaria gametophytes. Stimulated Petunia mesophyl protoplasts are arrested in G1 by olomoucine. By arresting cleavage it blocks the development of Calanus copepod larvae. It reversibly inhibits the early cleavages of Caenorhabditis elegans embryos and those of ascidian embryos. Olomoucine inhibits the serotonin-induced prophase/metaphase transition of clam oocytes; furthermore, it triggers the the release of these oocytes from their meiotic metaphase I arrest, and induces nuclei reformation. Olomoucine slows down the prophase/metaphase transition in cleaving sea urchin embryos, but does not affect the duration of the metaphase/anaphase and anaphase/telophase transitions. It also inhibits the prophase/metaphase transition of starfish oocytes triggered by various agonists. Xenopus oocyte maturation, the in vivo and in vitro phosphorylation of elongation factor EF-1 are inhibited by olomoucine. Mouse oocyte maturation is delayed by this compound, whereas parthenogenetic release from metaphase II arrest is facilitated. Growth of a variety of human cell lines (rhabdomyosarcoma cell lines Rh1, Rh18, Rh28 and Rh30; MCF-7, KB-3-1 and their adriamycin-resistant counterparts

  20. Operational and biological effects zones from base stations of cellular telephony

    SciTech Connect

    Geronikolou, St. A., E-mail: sgeronik@bioacademy.gr; Zimeras, S., E-mail: zimste@aegean.gr; Tsitomeneas, S. Th., E-mail: stsit@teipir.gr

    2016-03-25

    The possible environmental impacts of cellular base stations are operational and biological. The operational effects comprise Εlectro-Μagnetic Interference (EMI), lightning alterations and aesthetic degradation. Both thermal and non-thermal biological effects depend on the absorption of UHF radiofrequencies used. We measured, calculated and estimated the impact zones. The results are: (a) The lightning lethal zone equal to the antenna height, (b) the EMI impact in a zone up to 40m and (c) the ICNIRP’s limits exceed to a zone of 8∼20m into the antenna’s radiation pattern (for 2G GSM and 3G UMTS station). Finally we conclude the adverse effects must notmore » expected in a zone of more than 150m from the radiated antenna, whereas, there is possibility of stochastic effects in intermediate distances (20/40-150m).« less

  1. Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy.

    PubMed

    Di Pietro, C; Piro, S; Tabbì, G; Ragusa, M; Di Pietro, V; Zimmitti, V; Cuda, F; Anello, M; Consoli, U; Salinaro, E T; Caruso, M; Vancheri, C; Crimi, N; Sabini, M G; Cirrone, G A P; Raffaele, L; Privitera, G; Pulvirenti, A; Giugno, R; Ferro, A; Cuttone, G; Lo Nigro, S; Purrello, R; Purrello, F; Purrello, M

    2006-01-01

    Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.

  2. [Effect of electroacupuncture on cellular structure of hippocampus in splenic asthenia pedo-rats].

    PubMed

    Yang, Zhuo-xin; Zhuo, Yuan-yuan; Yu, Hai-bo; Wang, Ning

    2010-02-01

    To observe the effect of electroacupuncture (EA) on hippocampal structure in splenic asthenia pedo-rats. A total of 15 SD male rats were randomly assigned to normal control group (n=5), model group (n=5) and EA group (n=5). Splenic asthenic syndrome model was established by intragastric administration of rhubarb and intraperitoneal injection of Reserpine for 14 d. EA (1 mA, 3 Hz/iS Hz) was applied to bilateral "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 20 mm, once a day for 14 days. The cellular structure of hippocampus was observed by light microscope and transmission electron microscope. Optical microscopic observation showed that in normal control group, the cellular nucleus was distinct, and the granular cell layer well-arranged and tight. In model group, the intracellular space was widened, and the granular cell layer was out of order in the arrangement. In EA group, the celluldr nucleus and the granular cell layer were nearly normal. Results of the electronic microscope showed that cells in model group had a karyopyknosis with irregular appearance and clear incisure, and some of them presented dissolving and necrotic phenomena; and those in EA group were milder in injury, had nearly-normal nucleus with visible nucleoli and relatively-intact nuclear membrane. Regarding the cellular plasma, in comparison with rich normal organelles of control group, the mitochondria in model group were swelling, with vague, dissolved and broken cristae, while in EA group, majority of the organelles were well-kept, and slightly dissolved mitochondrial cristae found. In regard to the synaptic structure, in comparison with control group, synaptic apomorphosis and swelling mitochondria were found in model group While in EA group, milder swelling and hydropic degeneration were seen. Different from the distinct pre- and post-synaptic membrane and synaptic vesicles of control group, while those in EA group were nearly-normal. electroacupunture can effectively relieve splenasthenic

  3. Early Agriculture: Land Clearance and Climate Effects

    NASA Astrophysics Data System (ADS)

    Ruddiman, W. F.

    2013-12-01

    In the 2003 AGU Emiliani Lecture, I proposed the 'early anthropogenic hypothesis' --the idea that major anthropogenic effects on greenhouse gases and climate occurred thousands of years before the industrial era. In the decade since then, several dozen published papers have argued its pros and cons. In the 2013 Tyndall History of Global Change Lecture I will update where matters now stand. I will show figures from the 2003 Climate Change paper that laid out the initial hypothesis, and then update subsequent evidence from ice-core drilling, archeology, and land-use histories. The primary claims in the 2003 hypothesis were these: (1) the CH4 rise since 5000 years ago is anthropogenic; (2) the CO2 rise since 7000 years ago is also anthropogenic; (3) the amount of carbon emitted from preindustrial deforestation was roughly twice the amount released during the industrial era; (4) global temperature would have been cooler by about 0.8oC by the start of the industrial era if agricultural CO2 and CH4 emissions had not occurred; (5) early anthropogenic warming prevented the inception of new ice sheets at high northern latitudes; and (6) pandemics and other population catastrophes during the last 2000 years caused CO2 decreases lasting decades to centuries. The new evidence shows that these claims have held up well. The late-Holocene CO2 and CH4 rises are anomalous compared to average gas trends during previous interglaciations of the last 800,000 years. Land-use models based on historical data simulate pre-industrial CO2 carbon releases more than twice the industrial amounts. Archeological estimates of CH4 emissions from expanding rice irrigation account for much of the late Holocene CH4 rise, even without including livestock emissions or biomass burning. Model simulations show that the large pre-industrial greenhouse-gas emissions indicated by these historical and archeological estimates would have warmed global climate by more than 1oC and prevented northern glacial

  4. Effects of the endoparasitoid Cotesia chilonis (Hymenoptera: Braconidae) parasitism, venom, and calyx fluid on cellular and humoral immunity of its host Chilo suppressalis (Lepidoptera: Crambidae) larvae.

    PubMed

    Teng, Zi-Wen; Xu, Gang; Gan, Shi-Yu; Chen, Xuan; Fang, Qi; Ye, Gong-Yin

    2016-02-01

    The larval endoparasitoid Cotesia chilonis injects venom and bracoviruses into its host Chilo suppressalis during oviposition. Here we study the effects of the polydnavirus (PDV)-carrying endoparasitoid C. chilonis (Hymenoptera: Braconidae) parasitism, venom and calyx fluid on host cellular and humoral immunity, specifically hemocyte composition, cellular spreading, encapsulation and melanization. Total hemocyte counts (THCs) were higher in parasitized larvae than in unparasitized larvae in the late stages following parasitization. While both plasmatocyte and granulocyte fractions and hemocyte mortality did not differ between parasitized and unparasitized hosts, in vitro spreading behavior of hemocytes was inhibited significantly by parasitism throughout the course of parasitoid development. C. chilonis parasitism suppressed the encapsulation response and melanization in the early stages. Venom alone did not alter cellular immune responses, including effects on THCs, mortality, hemocyte composition, cell spreading and encapsulation, but venom did inhibit humoral immunity by reducing melanization within 6h after injection. In contrast to venom, calyx fluid had a significant effect on cell spreading, encapsulation and melanization from 6h after injection. Dose-response injection studies indicated the effects of venom and calyx fluid synergized, showing a stronger and more persistent reduction in immune system responses than the effect of either injected alone. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Modulatory effects of vitamin D on peripheral cellular immunity in patients with recurrent miscarriage.

    PubMed

    Chen, Xian; Yin, Biao; Lian, Ruo-Chun; Zhang, Tao; Zhang, Hong-Zhan; Diao, Liang-Hui; Li, Yu-Ye; Huang, Chun-Yu; Liang, De-Sheng; Zeng, Yong

    2016-12-01

    We aimed to investigate the modulatory effects of vitamin D on peripheral blood cellular immune response in patients with recurrent miscarriage (RM). The effect of vitamin D on the number of peripheral blood cells, T helper 1 (Th1) cytokines, and NK cytotoxicity was measured in 99 women with RM. The percentage of CD19 + B cells and NK cytotoxicity at an effector-to-target cell (E:T) ratio of 50:1, 25:1, and 12.5:1 were significantly higher in the vitamin D insufficiency group (VDI) than in the vitamin D normal group (VDN) (P<.05 each). The proportion of TNF-α-expressing Th cells was significantly higher in the vitamin D deficiency group (VDD) than in VDN (P<.05). However, there were no significant differences between VDI and VDD. This dysregulation was significantly reduced with 1,25(OH) 2 D supplementation. The data suggest that the abnormalities of cellular immune response were observed in RM patients with a low vitamin D level, which could be regulated to some extent with 1,25(OH) 2 D supplementation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Effects of helminths and Mycobacterium tuberculosis infection on HIV-1: a cellular immunological perspective.

    PubMed

    Mouser, Emily E I M; Pollakis, Georgios; Paxton, William A

    2012-05-01

    In many regions of the world, a high prevalence of HIV-1, helminthic and Mycobacterium tuberculosis (Mtb) infections can be found. Here, we summarize the types of immune responses induced and/or modulated by these pathogens and the consequences for HIV-1 disease. Helminths predominantly induce strong T helper (Th) 2 cellular responses which are downregulated in chronic disease. The anatomical niche populated by helminths plays a key factor in the effect these parasites have on HIV-1 transmission and subsequent replication. Gut-associated helminths have been found to increase HIV-1 transmission via the lesions they provide. In spite of this, the many immune modulatory molecules secreted by the parasites may inhibit or slow HIV-1 infection. In contrast, Mtb is mainly restricted to the lung and the Mtb-specific Th cells induced are highly susceptible to HIV-1 infection and replication. Antigens from both pathogens have immunomodulatory activity that can skew cellular immune responses in specific directions. The effect of helminths and Mtb on modulating immune responses is varied and complex with both their location and phenotype potentially influencing HIV-1 disease. These pathogens have evolved a complex array of molecules which have the capacity to modulate immunity and preserve pathogen survival.

  7. Effect of astragalus injection on serious abdominal traumatic patients' cellular immunity.

    PubMed

    Wu, Jian; Wang, Yi-xin; Su, Wen-li; Zhu, Wen-xian; Lu, Jing-wei; Li, Zhen-kai

    2006-03-01

    To explore the change of serious abdominal traumatic patients' cellular immunity and the effect of Astragalus Injection (AI) on it. Sixty-three serious abdominal traumatic patients were randomly assigned into two groups, the conventional group and the treated group, patients in the conventional group were given conventional treatment, while others in the treated group were given conventional treatment as the basis, with AI 20 ml was added into 250 ml of 5% glucose solution given through intravenous dripping, and then on the first day and 14th day, their T cell activated antigens as well as that of 10 healthy subjects were monitored. On the first day, in the conventional group and treated group, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), CD(16)(+), CD(69)(+) and CD(3)(+)/homologous leucocytic antigen-DR (HLA-DR(+)) were apparently lower than those in the healthy group (P < 0.05), while the CD(8)(+) was significantly higher than that in the healthy group (P < 0.05), and there was no significant difference between the conventional group and the treated group (P > 0.05); on the 14th days, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), CD(16)(+), CD(69)(+) and CD(3)(+)/HLA-DR(+) of the treated group got closed to healthy subject value, and got even higher than those of conventional group (P < 0.05); CD(8)(+) got close to that of healthy subjects, while obviously lower than that of conventional group (P < 0.05). After serious abdominal trauma, cellular immunity lowered, auxiliary use of AI was beneficial to the restoration of cellular immunity.

  8. Cellular effect of styrene substituted biscoumarin caused cellular apoptosis and cell cycle arrest in human breast cancer cells.

    PubMed

    Perumalsamy, Haribalan; Sankarapandian, Karuppasamy; Kandaswamy, Narendran; Balusamy, Sri Renukadevi; Periyathambi, Dhaiveegan; Raveendiran, Nanthini

    2017-11-01

    Coumarins occurs naturally across plant kingdoms exhibits significant pharmacological properties and pharmacokinetic activity. The conventional, therapeutic agents are often associated with poor stability, absorption and increased side effects. Therefore, identification of a drug that has little or no-side effect on humans is consequential. Here, we investigated the antiproliferative activity of styrene substituted biscoumarin against various human breast cancer cell lines, such as MCF-7, (ER-) MDA-MB-231 and (AR+) MDA-MB-453. Styrene substituted biscoumarin induced cell death by apoptosis in MDA-MB-231 cell line was analyzed. Antiproliferative activity of Styrene substituted biscoumarin was performed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Styrene substituted biscoumarin induced apoptosis was assessed by Hoechst staining, Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining and flow cytometric analysis. Migratory and proliferating characteristic of breast cancer cell line MDA-MB-231 was also analyzed by wound healing and colony formation assay. Furthermore, mRNA expression of BAX and BCL-2 were quantified using qRT-PCR and protein expression level analyzed by Western blot. The inhibition concentration (IC 50 ) of styrene substituted biscoumarin was assayed against three breast cancer cell lines. The inhibition concentration (IC 50 ) value of styrene substituted biscoumarin toward MDA-MB-231, MDA-MB-453 and MCF-7 cell lines was 5.63, 7.30 and 10.84μg/ml respectively. Styrene substituted biscoumarin induced apoptosis was detected by Hoechst staining, DAPI/PI analysis and flow-cytometric analysis. The migration and proliferative efficiency of MDA-MB-231 cells were completely arrested upon styrene substituted biscoumarin treatment. Also, mRNA gene expression and protein expression of pro-apoptotic (BAX) and anti-apoptotic (BCL-2) genes were analyzed by qRT-PCR and western blot analysis upon

  9. Independent cellular effects of cold ischemia and reperfusion: experimental molecular study.

    PubMed

    Lledó-García, E; Humanes-Sánchez, B; Mojena-Sánchez, M; Rodrígez, J C J; Hernández-Fernández, C; Tejedor-Jorge, A; Fernández, A L

    2013-04-01

    There is less information available on cell cultures on the exclusive effects of either duration of cold ischemia (CI) or rewarming-reperfusion in the kidney subjected to initial warm ischemia (WI). Therefore, the goals of our work were: (1) to evaluate the consequences on tubular cellular viability of different durations of CI on a kidney after an initial period of WI, and (2) to analyze the additional effect on tubular cell viability of rewarming of the same kidney. Sixteen mini-pig were used. All the animals were performed a right nephrectomy after 45-minute occlusion of the vascular pedicle. The kidneys were then divided into 2 groups (phase 1): cold storage in university of wisconsin (UW) solution for 3 hours (group A, n = 8) at 4°C, or cold storage in UW for 12 hours (group B, n = 8) at 4°C. Four organs of group A and four organs of group B were autotrasplanted (AT) and reperfused for 1 hour (phase 2). Nephrectomy was finally done. Biopsies were taken from all groups to perform cultures of proximal tubule epithelium cells. The biopsies were subjected to studies of cellular morphological viability (contrast phase microscopy [CPM]) and quantitative (confluence cell [CC]) parameters. Phase of pure CI effects (phase 1): Both CC rate and CPM parameters were significantly lower in group B compared with group A, where cell activity reached almost normal results. Phase of CI + AT (phase 2): At produced additional harmful effects in cell cultures compared with those obtained in phase 1, more evident in group B cells. The presence of cold storage followed by rewarming-reperfusion induces independent and cumulative detrimental effects in viability of renal proximal tubule cells. CI periods ≤ 3 hours may ameliorate the injuries secondary to reperfusion in comparison with longer CI periods. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Effects of Matrix Alignment and Mechanical Constraints on Cellular Behavior in 3D Engineered Microtissues

    NASA Astrophysics Data System (ADS)

    Bose, Prasenjit; Eyckmans, Jeroen; Chen, Christopher; Reich, Daniel

    The adhesion of cells to the extracellular matrix (ECM) plays a crucial role in a variety of cellular functions. The main building blocks of the ECM are 3D networks of fibrous proteins whose structure and alignments varies with tissue type. However, the impact of ECM alignment on cellular behaviors such as cell adhesion, spreading, extension and mechanics remains poorly understood. We present results on the development of a microtissue-based system that enables control of the structure, orientation, and degree of fibrillar alignment in 3D fibroblast-populated collagen gels. The tissues self-assemble from cell-laden collagen gels placed in micro-fabricated wells containing sets of elastic pillars. The contractile action of the cells leads to controlled alignment of the fibrous collagen, depending on the number and location of the pillars in each well. The pillars are elastic, and are utilized to measure the contractile forces of the microtissues, and by incorporating magnetic material in selected pillars, time-varying forces can be applied to the tissues for dynamic stimulation and measurement of mechanical properties. Results on the effects of varying pillar shape, spacing, location, and stiffness on microtissue organization and contractility will be presented. This work is supported by NSF CMMI-1463011.

  11. Effects of modified FOLFOX-6 chemotherapy on cellular immune function in patients with gastric cancer

    PubMed Central

    Wang, Liang; Zhou, Donger; Ren, Haitao; Chen, Yan

    2018-01-01

    Tumor immunosuppression serves an important role in the occurrence and development of gastric cancer. However, the effect of chemotherapy on the immune function of patients remains unclear. The present study aimed to investigate changes in cellular immune function and regulatory T cells (Tregs) in patients with gastric cancer prior to and following chemotherapy. In the peripheral blood of patients with gastric cancer, the percentage of CD4+ T cells was substantially decreased compared with that of healthy controls (11.39±5.91 vs. 22.34±3.37%, respectively; P<0.05). High frequencies of CD8+ T cells and Tregs were also observed in the peripheral blood of patients. Although the number of T cells decreased following chemotherapy (the proportions of CD4+ and CD8+ cells were 8.99±7.31 and 16.00±4.51%, respectively), the ratio of CD4+/CD8+ T cells increased (0.31±0.17 vs. 0.56±0.22; P<0.05). Furthermore, the level of C-C motif chemokine ligand 20 (CCL20) was increased in patients prior to chemotherapy compared with healthy controls. As the sole receptor for CCL20, a high level of expression of C-C motif chemokine receptor 6 on circulating Tregs was also identified in the patients, which decreased following chemotherapy. These results suggest that chemotherapy may efficiently promote cellular immune function and inhibit immunosuppression in patients with gastric cancer.

  12. Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

    PubMed Central

    Balentova, Sona; Adamkov, Marian

    2015-01-01

    Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

  13. The effects of Cosmos caudatus (ulam raja) on dynamic and cellular bone histomorphometry in ovariectomized rats

    PubMed Central

    2013-01-01

    Background Cosmos caudatus is a local plant which has antioxidant properties and contains high calcium. It is also reported to be able to strengthen the bone. This report is an extension to previously published article in Evidence Based Complementary and Alternative Medicine (doi:10.1155/2012/817814). In this study, we determined the effectiveness of C. caudatus as an alternative treatment for osteoporosis due to post-menopause by looking at the dynamic and cellular paramaters of bone histomorphometry. Methods Forty female Wistar rats were divided into four groups i.e. sham operated, ovariectomized, ovariectomized treated with calcium 1% ad libitum and ovariectomized force-fed with 500 mg/kg C. caudatus extract. Treatment was given six days a week for eight weeks. Results Dynamic and cellular histomorphometry parameters were measured. C. caudatus increased double-labeled surface (dLS/BS), mineral appositional rate (MAR), osteoid volume (OV/BV) and osteoblast surface (Ob.S/BS). C. caudatus also gave better results compared to calcium 1% in the osteoid volume (OV/BV) parameter. Conclusions C. caudatus at the 500 mg/kg dose may be an alternative treatment in restoring bone damage that may occur in post-menopausal women. PMID:23800238

  14. The effects of Cosmos caudatus (ulam raja) on dynamic and cellular bone histomorphometry in ovariectomized rats.

    PubMed

    Mohamed, Norazlina; Sahhugi, Zulaikha; Ramli, Elvy Suhana Mohd; Muhammad, Norliza

    2013-06-24

    Cosmos caudatus is a local plant which has antioxidant properties and contains high calcium. It is also reported to be able to strengthen the bone. This report is an extension to previously published article in Evidence Based Complementary and Alternative Medicine (doi:10.1155/2012/817814). In this study, we determined the effectiveness of C. caudatus as an alternative treatment for osteoporosis due to post-menopause by looking at the dynamic and cellular paramaters of bone histomorphometry. Forty female Wistar rats were divided into four groups i.e. sham operated, ovariectomized, ovariectomized treated with calcium 1% ad libitum and ovariectomized force-fed with 500 mg/kg C. caudatus extract. Treatment was given six days a week for eight weeks. Dynamic and cellular histomorphometry parameters were measured. C. caudatus increased double-labeled surface (dLS/BS), mineral appositional rate (MAR), osteoid volume (OV/BV) and osteoblast surface (Ob.S/BS). C. caudatus also gave better results compared to calcium 1% in the osteoid volume (OV/BV) parameter. C. caudatus at the 500 mg/kg dose may be an alternative treatment in restoring bone damage that may occur in post-menopausal women.

  15. NAXE Mutations Disrupt the Cellular NAD(P)HX Repair System and Cause a Lethal Neurometabolic Disorder of Early Childhood.

    PubMed

    Kremer, Laura S; Danhauser, Katharina; Herebian, Diran; Petkovic Ramadža, Danijela; Piekutowska-Abramczuk, Dorota; Seibt, Annette; Müller-Felber, Wolfgang; Haack, Tobias B; Płoski, Rafał; Lohmeier, Klaus; Schneider, Dominik; Klee, Dirk; Rokicki, Dariusz; Mayatepek, Ertan; Strom, Tim M; Meitinger, Thomas; Klopstock, Thomas; Pronicka, Ewa; Mayr, Johannes A; Baric, Ivo; Distelmaier, Felix; Prokisch, Holger

    2016-10-06

    To safeguard the cell from the accumulation of potentially harmful metabolic intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding the accumulation of toxic metabolites. The clinical importance of the NAD(P)HX repair system has been unknown. Exome sequencing revealed pathogenic biallelic mutations in NAXE in children from four families with (sub-) acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions. Lactate was elevated in cerebrospinal fluid of all affected individuals. Disease onset was during the second year of life and clinical signs as well as episodes of deterioration were triggered by febrile infections. Disease course was rapidly progressive, leading to coma, global brain atrophy, and finally to death in all affected individuals. NAXE levels were undetectable in fibroblasts from affected individuals of two families. In these fibroblasts we measured highly elevated concentrations of the toxic metabolite cyclic-NADHX, confirming a deficiency of the mitochondrial NAD(P)HX repair system. Finally, NAD or nicotinic acid (vitamin B3) supplementation might have therapeutic implications for this fatal disorder. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Effects of HIV-1 protease on cellular functions and their potential applications in antiretroviral therapy

    PubMed Central

    2012-01-01

    Human Immunodeficiency Virus Type 1 (HIV-1) protease inhibitors (PIs) are the most potent class of drugs in antiretroviral therapies. However, viral drug resistance to PIs could emerge rapidly thus reducing the effectiveness of those drugs. Of note, all current FDA-approved PIs are competitive inhibitors, i.e., inhibitors that compete with substrates for the active enzymatic site. This common inhibitory approach increases the likelihood of developing drug resistant HIV-1 strains that are resistant to many or all current PIs. Hence, new PIs that move away from the current target of the active enzymatic site are needed. Specifically, allosteric inhibitors, inhibitors that prohibit PR enzymatic activities through non-competitive binding to PR, should be sought. Another common feature of current PIs is they were all developed based on the structure-based design. Drugs derived from a structure-based strategy may generate target specific and potent inhibitors. However, this type of drug design can only target one site at a time and drugs discovered by this method are often associated with strong side effects such as cellular toxicity, limiting its number of target choices, efficacy, and applicability. In contrast, a cell-based system may provide a useful alternative strategy that can overcome many of the inherited shortcomings associated with structure-based drug designs. For example, allosteric PIs can be sought using a cell-based system without considering the site or mechanism of inhibition. In addition, a cell-based system can eliminate those PIs that have strong cytotoxic effect. Most importantly, a simple, economical, and easy-to-maintained eukaryotic cellular system such as yeast will allow us to search for potential PIs in a large-scaled high throughput screening (HTS) system, thus increasing the chances of success. Based on our many years of experience in using fission yeast as a model system to study HIV-1 Vpr, we propose the use of fission yeast as a possible

  17. Adenovirus Type 5 Early Region 1B 55K Oncoprotein-Dependent Degradation of Cellular Factor Daxx Is Required for Efficient Transformation of Primary Rodent Cells▿

    PubMed Central

    Schreiner, Sabrina; Wimmer, Peter; Groitl, Peter; Chen, Shuen-Yuan; Blanchette, Paola; Branton, Philip E.; Dobner, Thomas

    2011-01-01

    Early region 1B 55K (E1B-55K) from adenovirus type 5 (Ad5) is a multifunctional regulator of lytic infection and contributes in vitro to complete cell transformation of primary rodent cells in combination with Ad5 E1A. Inhibition of p53 activated transcription plays a key role in processes by which E1B-55K executes its oncogenic potential. Nevertheless, additional functions of E1B-55K or further protein interactions with cellular factors of DNA repair, transcription, and apoptosis, including Mre11, PML, and Daxx, may also contribute to the transformation process. In line with previous results, we performed mutational analysis to define a Daxx interaction motif within the E1B-55K polypeptide. The results from these studies showed that E1B-55K/Daxx binding is not required for inhibition of p53-mediated transactivation or binding and degradation of cellular factors (p53/Mre11). Surprisingly, these mutants lost the ability to degrade Daxx and showed reduced transforming potential in primary rodent cells. In addition, we observed that E1B-55K lacking the SUMO-1 conjugation site (SCS/K104R) was sufficient for Daxx interaction but no longer capable of E1B-55K-dependent proteasomal degradation of the cellular factor Daxx. These results, together with the observation that E1B-55K SUMOylation is required for efficient transformation, provides evidence for the idea that SUMO-1-conjugated E1B-55K-mediated degradation of Daxx plays a key role in adenoviral oncogenic transformation. We assume that the viral protein contributes to cell transformation through the modulation of Daxx-dependent pathways. This further substantiates the assumption that further mechanisms for efficient transformation of primary cells can be separated from functions required for the inhibition of p53-stimulated transcription. PMID:21697482

  18. Biological effects of electric shock and heat denaturation and oxidation of molecules, membranes, and cellular functions.

    PubMed

    Tsong, T Y; Su, Z D

    1999-10-30

    Direct exposure of cells in suspension to intense electric pulses is known to produce damages to cell membranes and supramolecular organizations of cells, and denaturation of macromolecules, much like injuries and tears seen in electric trauma patients. Thus, the system has been used as a laboratory model for investigating the biochemical basis of electric injury. An intense electric pulse can produce two major effects on cells--one caused by the field, or the electric potential, and the other by current, or the electric energy. The field-induced transmembrane potential can produce electro-conformational changes of ion channels and ion pumps and, when the potential exceeds the dielectric strength of the cell membrane (approximately 500 mV for a pulse width of a few ms), electro-conformational damages and electroporations of membrane proteins and lipid bilayers. These events lead to passage of electric current through the membrane-porated cells and to heating of cell membranes and cytoplasmic contents. The subsequent denaturation of cell membranes and cytoplasmic macromolecules brings about many complex biochemical reactions, including oxidation of proteins and lipids. The combined effects may cripple the cells beyond repair. This communication will focus on the thermal effects of electric shock. After a brief review of the current state of knowledge on thermal denaturation of soluble enzymes and muscle proteins, this paper will describe experiments on the thermal denaturation of cellular components and functions, such as nucleosomes, and the electron transport chain and ATP synthetic enzymes of the mitochondrial inner membranes. Data will show that lipid peroxidation and the subsequent loss of the energy-transducing ability of the cells may occur even at moderate temperatures between 40 degrees C and 45 degrees C. However, lipid peroxidation may be prevented with reducing reagents such as mercaptoethanol, dithiothreitol, and ascorbic acid. Reactivation of denatured

  19. Effects of brevetoxins on murine myeloma SP2/O cells: Aberrant cellular division

    USGS Publications Warehouse

    Han, T.K.; Derby, M.; Martin, D.F.; Wright, S.D.; Dao, M.L.

    2003-01-01

    Massive deaths of manatees (Trichechus manatus latirostris) during the red tide seasons have been attributed to brevetoxins produced by the dinoflagellate Karenia brevis (formerly Ptychodiscus breve and Gymnodinium breve). Although these toxins have been found in macrophages and lymphocytes in the lung, liver, and secondary lymphoid tissues of these animals, the molecular mechanisms of brevetoxicosis have not yet been identified. To investigate the effects of brevetoxins on immune cells, a murine myeloma cell line (SP2/O) was used as a model for in vitro studies. By adding brevetoxins to cultures of the SP2/O cells at concentrations ranging from 20 to 600 ng/ml, an apparent increase in proliferation was observed at around 2 hours post challenge as compared to the unchallenged cell cultures. This was followed by a drop in cell number at around 3 hours, suggesting an aberrant effect of brevetoxins on cellular division, the cells generated at 2 hours being apparently short-lived. In situ immunochemical staining of the SP2/O cells at 1 and 2 hour post challenge showed an accumulation of the toxins in the nucleus. A 21-kDa protein was subsequently isolated from the SP2/O cells as having brevetoxin-binding properties, and immunologically identified as p21, a nuclear factor known to down-regulate cellular proliferation through inhibition of cyclin-dependent kinases. These data are the first on a possible effect of brevetoxins on the cell cycle via binding to p21, a phenomenon that needs to be further investigated and validated in normal immune cells.

  20. Dendritic cells are early cellular targets of Listeria monocytogenes after intestinal delivery and are involved in bacterial spread in the host.

    PubMed

    Pron, B; Boumaila, C; Jaubert, F; Berche, P; Milon, G; Geissmann, F; Gaillard, J L

    2001-05-01

    We studied the sequence of cellular events leading to the dissemination of Listeria monocytogenes from the gut to draining mesenteric lymph nodes (MLNs) by confocal microscopy of immunostained tissue sections from a rat ligated ileal loop system. OX-62-positive cells beneath the epithelial lining of Peyer's patches (PPs) were the first Listeria targets identified after intestinal inoculation. These cells had other features typical of dendritic cells (DCs): they were large, pleiomorphic and major histocompatibility complex class II(hi). Listeria were detected by microscopy in draining MLNs as early as 6 h after inoculation. Some 80-90% of bacteria were located in the deep paracortical regions, and 100% of the bacteria were present in OX-62-positive cells. Most infected cells contained more than five bacteria each, suggesting that they had arrived already loaded with bacteria. At later stages, the bacteria in these areas were mostly present in ED1-positive mononuclear phagocytes. These cells were also infected by an actA mutant defective in cell-to-cell spreading. This suggests that Listeria are transported by DCs from PPs to the deep paracortical regions of draining MLNs and are then transmitted to other cell populations by mechanisms independent of ActA. Another pathway of dissemination to MLNs was identified, probably involving free Listeria and leading to the infection of ED3-positive mononuclear phagocytes in the subcapsular sinus and adjacent paracortical areas. This study provides evidence that DCs are major cellular targets of L. monocytogenes in PPs and that DCs may be involved in the early dissemination of this pathogen. DCs were not sites of active bacterial replication, making these cells ideal vectors of infection.

  1. Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens.

    PubMed Central

    Newbold, R

    1995-01-01

    Concerns have been raised regarding the role of environmental and dietary estrogens as possible contributors to an increased incidence of various abnormalities in estrogen-target tissues of both sexes. These abnormalities include breast cancer, endometriosis, fibroids, and uterine adenocarcinoma in females, as well as alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems in males. Whether these concerns are valid remains to be determined; however, studies with the potent synthetic estrogen diethylstilbestrol (DES) suggest that exogenous estrogen exposure during critical stages of development can result in permanent cellular and molecular alterations in the exposed organism. These alterations manifest themselves in the female and male as structural, functional, or long-term pathological changes including neoplasia. Although DES has potent estrogenic activity, it may be used as a model compound to study the effects of weaker environmental estrogens, many of which may fit into the category of endocrine disruptors. PMID:8593881

  2. Uptake of polycyclic aromatic hydrocarbons and their cellular effects in the mangrove Bruguiera gymnorrhiza.

    PubMed

    Naidoo, Gonasageran; Naidoo, Krishnaveni

    2016-12-15

    The uptake of polycyclic aromatic hydrocarbons and their cellular effects were investigated in the mangrove Bruguiera gymnorrhiza. Seedlings were subjected to sediment oiling for three weeks. In the oiled treatment, the ƩPAHs was higher in roots (99%) than in leaves (1%). In roots, PAHs included phenanthrene (55%), acenaphthene (13%), fluorine (12%) and anthracene (8%). In leaves, PAHs possessed two to three rings and included acenaphthene (35%), naphthalene (33%), fluorine (18%) and phenanthrene (14%). In the roots, oil caused disorganization of cells in the root cap, meristem and conducting tissue. Oil contaminated cells were distorted and possessed large and irregularly shaped vacuoles. Ultrastructural changes included loss of cell contents and fragmentation of the nucleus and mitochondrion. In the leaves, oil caused dilation and distortion of chloroplasts and disintegration of grana and lamellae. Oil targets critical organelles such as nuclei, chloroplasts and mitochondria which are responsible for cell vitality and energy transformation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Effects of Atmospheric Pressure Plasmas on Isolated and Cellular DNA—A Review

    PubMed Central

    Arjunan, Krishna Priya; Sharma, Virender K.; Ptasinska, Sylwia

    2015-01-01

    Atmospheric Pressure Plasma (APP) is being used widely in a variety of biomedical applications. Extensive research in the field of plasma medicine has shown the induction of DNA damage by APP in a dose-dependent manner in both prokaryotic and eukaryotic systems. Recent evidence suggests that APP-induced DNA damage shows potential benefits in many applications, such as sterilization and cancer therapy. However, in several other applications, such as wound healing and dentistry, DNA damage can be detrimental. This review reports on the extensive investigations devoted to APP interactions with DNA, with an emphasis on the critical role of reactive species in plasma-induced damage to DNA. The review consists of three main sections dedicated to fundamental knowledge of the interactions of reactive oxygen species (ROS)/reactive nitrogen species (RNS) with DNA and its components, as well as the effects of APP on isolated and cellular DNA in prokaryotes and eukaryotes. PMID:25642755

  4. Effects of atmospheric pressure plasmas on isolated and cellular DNA-a review.

    PubMed

    Arjunan, Krishna Priya; Sharma, Virender K; Ptasinska, Sylwia

    2015-01-29

    Atmospheric Pressure Plasma (APP) is being used widely in a variety of biomedical applications. Extensive research in the field of plasma medicine has shown the induction of DNA damage by APP in a dose-dependent manner in both prokaryotic and eukaryotic systems. Recent evidence suggests that APP-induced DNA damage shows potential benefits in many applications, such as sterilization and cancer therapy. However, in several other applications, such as wound healing and dentistry, DNA damage can be detrimental. This review reports on the extensive investigations devoted to APP interactions with DNA, with an emphasis on the critical role of reactive species in plasma-induced damage to DNA. The review consists of three main sections dedicated to fundamental knowledge of the interactions of reactive oxygen species (ROS)/reactive nitrogen species (RNS) with DNA and its components, as well as the effects of APP on isolated and cellular DNA in prokaryotes and eukaryotes.

  5. [Effects of different trophic modes on growth characteristics, metabolism and cellular components of Chlorella vulgaris].

    PubMed

    Kong, Weibao; Wang, Yang; Yang, Hong; Xi, Yuqin; Han, Rui; Niu, Shiquan

    2015-03-04

    We studied the effects of trophic modes related to glucose and light (photoautotrophy, mixotrophy and heterotrophy) on growth, cellular components and carbon metabolic pathway of Chlorella vulgaris. The parameters about growth of algal cells were investigated by using spectroscopy and chromatography techniques. When trophic mode changed from photoautotrophy to mixotrophy and to heterotrophy successively, the concentrations of soluble sugar, lipid and saturated C16/C18 fatty acids in C. vulgaris increased, whereas the concentrations of unsaturated C16, C18 fatty acids, proteins, photosynthetic pigments and 18 relative amino acids decreased. Light and glucose affect the growth, metabolism and the biochemical components biosynthesis of C. vulgaris. Addition of glucose can promote algal biomass accumulation, stimulate the synthesis of carbonaceous components, but inhibit nitrogenous components. Under illumination cultivation, concentration and consumption level of glucose decided the main trophic modes of C. vulgaris. Mixotrophic and heterotrophic cultivation could promote the growth of algal cells.

  6. Temperature Effects on Olive Fruit Fly Infestation in the FlySim Cellular Automata Model

    NASA Astrophysics Data System (ADS)

    Bruno, Vincenzo; Baldacchini, Valerio; di Gregorio, Salvatore

    FlySim is a Cellular Automata model developed for simulating infestation of olive fruit flies (Bactrocera Oleae) on olive (Olea europaea) groves. The flies move into the groves looking for mature olives where eggs are spawn. This serious agricultural problem is mainly tackled by using chemical agents at the first signs of the infestation, but organic productions with no or few chemicals are strongly requested by the market. Oil made with infested olives is poor in quality, nor olives are suitable for selling in stores. The FlySim model simulates the diffusion of flies looking for mature olives and the growing of flies due to atmospheric conditions. Foreseeing an infestation is the best way to prevent it and to reduce the need of chemicals in agriculture. In this work we investigated the effects of temperature on olive fruit flies and resulting infestation during late spring and summer.

  7. [Effect of phenolic ketones on ethanol fermentation and cellular lipid composition of Pichia stipitis].

    PubMed

    Yang, Jinlong; Cheng, Yichao; Zhu, Yuanyuan; Zhu, Junjun; Chen, Tingting; Xu, Yong; Yong, Qiang; Yu, Shiyuan

    2016-02-01

    Lignin degradation products are toxic to microorganisms, which is one of the bottlenecks for fuel ethanol production. We studied the effects of phenolic ketones (4-hydroxyacetophenone, 4-hydroxy-3-methoxy-acetophenone and 4-hydroxy-3,5-dimethoxy-acetophenone) derived from lignin degradation on ethanol fermentation of xylose and cellular lipid composition of Pichia stipitis NLP31. Ethanol and the cellular fatty acid of yeast were analyzed by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Results indicate that phenolic ketones negatively affected ethanol fermentation of yeast and the lower molecular weight phenolic ketone compound was more toxic. When the concentration of 4-hydroxyacetophenone was 1.5 g/L, at fermentation of 24 h, the xylose utilization ratio, ethanol yield and ethanol concentration decreased by 42.47%, 5.30% and 9.76 g/L, respectively, compared to the control. When phenolic ketones were in the medium, the ratio of unsaturated fatty acids to saturated fatty acids (UFA/SFA) of yeast cells was improved. When 1.5 g/L of three aforementioned phenolic ketones was added to the fermentation medium, the UFA/SFA ratio of yeast cells increased to 3.03, 3.06 and 3.61, respectively, compared to 2.58 of the control, which increased cell membrane fluidity and instability. Therefore, phenolic ketones can reduce the yeast growth, increase the UFA/SFA ratio of yeast and lower ethanol productivity. Effectively reduce or remove the content of lignin degradation products is the key to improve lignocellulose biorefinery.

  8. The effectiveness of cardiopulmonary resuscitation instruction: animation versus dispatcher through a cellular phone.

    PubMed

    Choa, Minhong; Park, Incheol; Chung, Hyun Soo; Yoo, Sun K; Shim, Hoshik; Kim, Seungho

    2008-04-01

    We developed a cardiopulmonary resuscitation (CPR) instruction programme using motion capture animation integrated into cellular phones. We compared the effectiveness of animation-assisted CPR instruction with dispatcher-assisted instruction in participants with no previous CPR training. This study was a single blind cluster randomized trial. Participants were allocated to either animation-assisted CPR (AA-CPR; 8 clusters, 44 participants) group or dispatcher-assisted CPR (DA-CPR; 8 clusters, 41 participants). The overall performance and time of each step of CPR cycle were recorded on a checklist by 3 assessors. The objective performances were evaluated using the Resusci Anne SkillReporter Manikin. Differences between the groups were compared using an independent t-test adjusted for the effect of clustering. The AA-CPR group had a significantly better checklist score (p<0.001) and time to completion of 1 CPR cycle (p<0.001) than the DA-CPR group. In an objective assessment of psychomotor skill, the AA-CPR group demonstrated more accurate hand positioning (68.8+/-3.6%, p=0.033) and compression rate (72.4+/-3.7%, p=0.015) than DA-CPR group. However, the accuracy of compression depth (p=0.400), ventilation volume (p=0.977) and flow rate (p=0.627) were below 30% in both groups. Audiovisual animated CPR instruction through a cellular phone resulted in better scores in checklist assessment and time interval compliance in participants without CPR skill compared to those who received CPR instructions from a dispatcher; however, the accuracy of important psychomotor skill measures was unsatisfactory in both groups.

  9. Cellular Antioxidant and Anti-Inflammatory Effects of Coffee Extracts with Different Roasting Levels.

    PubMed

    Jung, Soohan; Kim, Min Hyung; Park, Jae Hee; Jeong, Yoonhwa; Ko, Kwang Suk

    2017-06-01

    During roasting, major changes occur in the composition and physiological effects of coffee beans. In this study, in vitro antioxidant effects and anti-inflammatory effects of Coffea arabica green coffee extracts were investigated at different roasting levels corresponding to Light, Medium, City, and French roast. Total caffeine did not show huge difference according to roasting level, but total chlorogenic acid contents were higher in light roasted coffee extract than other roasted groups. In addition, light roasted coffee extract had the highest antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. To determine the in vitro antioxidant property, coffee extracts were used to treat AML-12 cells. Intracellular glutathione (GSH) concentration and mRNA expression levels of genes related to GSH synthesis were negatively related to roasting levels. The anti-inflammatory effects of coffee extracts were investigated in lipopolysaccharide-treated RAW 264.7 macrophage cells. The cellular antioxidant activity of coffee extracts exhibited similar patterns as the AML-12 cells. The expression of mRNA for tumor necrosis factor-alpha and interleukin-6 was decreased in cells treated with the coffee extracts and the expression decreased with increasing roasting levels. These data suggest that coffee has physiological antioxidant and anti-inflammatory activities and these effects are negatively correlated with roasting levels in the cell models.

  10. Theoretical models and simulation codes to investigate bystander effects and cellular communication at low doses

    NASA Astrophysics Data System (ADS)

    Ballarini, F.; Alloni, D.; Facoetti, A.; Mairani, A.; Nano, R.; Ottolenghi, A.

    Astronauts in space are continuously exposed to low doses of ionizing radiation from Galactic Cosmic Rays During the last ten years the effects of low radiation doses have been widely re-discussed following a large number of observations on the so-called non targeted effects in particular bystander effects The latter consist of induction of cytogenetic damage in cells not directly traversed by radiation most likely as a response to molecular messengers released by directly irradiated cells Bystander effects which are observed both for lethal endpoints e g clonogenic inactivation and apoptosis and for non-lethal ones e g mutations and neoplastic transformation tend to show non-linear dose responses This might have significant consequences in terms of low-dose risk which is generally calculated on the basis of the Linear No Threshold hypothesis Although the mechanisms underlying bystander effects are still largely unknown it is now clear that two types of cellular communication i e via gap junctions and or release of molecular messengers into the extracellular environment play a fundamental role Theoretical models and simulation codes can be of help in elucidating such mechanisms In the present paper we will review different available modelling approaches including one that is being developed at the University of Pavia The focus will be on the different assumptions adopted by the various authors and on the implications of such assumptions in terms of non-targeted radiobiological damage and more generally low-dose

  11. [Effects of electromagnetic field from cellular phones on selected central nervous system functions: a literature review].

    PubMed

    Bak, Marek; Zmyślony, Marek

    2010-01-01

    In the opinion of some experts, a growing emission of man-made electromagnetic fields (EMF), also known as electromagnetic is a source of continuously increasing health hazards to the general population. Due to their large number and very close proximity to the user's head, mobile phones deserve special attention. This work is intended to give a systematic review of objective studies, assessing the effects of mobile phone EMF on the functions of the central nervous system (CNS) structures. Our review shows that short exposures to mobile phone EMF, experienced by telephone users during receiving calls, do not affect the cochlear function. Effects of GSM mobile phone EMF on the conduction of neural impulses from the inner car neurons to the brainstem auditory centres have not been detected either. If Picton's principle, saying that P300 amplitude varies with the improbability of the targets and its latency varies with difficulty of discriminating the target stimulus from standard stimuli, is true, EMF changes the improbability of the targets without hindering their discrimination. Experiments with use of indirect methods do not enable unequivocal verification of EMF effects on the cognitive functions due to the CNS anatomical and functional complexity. Thus, it seems advisable to develop a model of EMF effects on the excitable brain structures at the cellular level.

  12. Evaluation of the dispersion effect in through movement bicycles at signalized intersection via cellular automata simulation

    NASA Astrophysics Data System (ADS)

    Jiang, Hang; Ma, Yongjian; Jiang, Lin; Chen, Guozhou; Wang, Dongwei

    2018-05-01

    At signalized intersection areas, bicycle traffic presents a dispersion feature which may influence the movements of vehicles during peak period. The primary objective of this study is to simulate the dispersion effect in through-movement bicycle traffic at intersection areas and evaluate its influence on through-movement traffic. A cellular automata (CA) model is developed and validated to simulate the operations of through-movement bicycle traffic departing from two types of intersection approaches. Simulation results show that bicycles benefit from the dispersion effect when they depart from the approach with an exclusive right-turn vehicle lane. But when bicycles travel from the approach with a shared right-turn and through vehicle lane, the dispersion effect will result in friction interference and block interference on through-movement vehicles. Bicycle interferences reduce the vehicle speed and increase the delay of through-movement vehicles. The policy implications in regard to the dispersion effect from two types of approaches are discussed to improve the performance of through-movement traffic operations at signalized intersections.

  13. Cognitive effects of radiation emitted by cellular phones: the influence of exposure side and time.

    PubMed

    Luria, Roy; Eliyahu, Ilan; Hareuveny, Ronen; Margaliot, Menachem; Meiran, Nachshon

    2009-04-01

    This study examined the time dependence effects of exposure to radiofrequency radiation (RFR) emitted by standard GSM cellular phones on the cognitive functions of humans. A total of 48 healthy right-handed male subjects performed a spatial working memory task (that required either a left-hand or a right-hand response) while being exposed to one of two GSM phones placed at both sides of the head. The subjects were randomly divided into three groups. Each group was exposed to one of three exposure conditions: left-side of the head, right-side, or sham-exposure. The experiment consisted of 12 blocks of trials. Response times (RTs) and accuracy of the responses were recorded. It was found that the average RT of the right-hand responses under left-side exposure condition was significantly longer than those of the right-side and sham-exposure groups averaged together during the first two time blocks. These results confirmed the existence of an effect of exposure on RT, as well as the fact that exposure duration (together with the responding hand and the side of exposure) may play an important role in producing detectable RFR effects on performance. Differences in these parameters might be the reason for the failure of certain studies to detect or replicate RFR effects. (c) 2008 Wiley-Liss, Inc.

  14. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis.

    PubMed

    Borow, Kenneth M; Nelson, John R; Mason, R Preston

    2015-09-01

    Residual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive statin therapy, underscoring the need for additional intervention. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into membrane phospholipids and atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through rupture. Specific salutary actions have been reported relating to endothelial function, oxidative stress, foam cell formation, inflammation, plaque formation/progression, platelet aggregation, thrombus formation, and plaque rupture. EPA also improves atherogenic dyslipidemia characterized by reduction of triglycerides without raising low-density lipoprotein cholesterol. Other beneficial effects of EPA include vasodilation, resulting in blood pressure reductions, as well as improved membrane fluidity. EPA's effects are at least additive to those of statins when given as adjunctive therapy. In this review, we present data supporting the biologic plausibility of EPA as an anti-atherosclerotic agent with potential clinical benefit for prevention of CV events, as well as its cellular effects and molecular mechanisms of action. REDUCE-IT is an ongoing, randomized, controlled study evaluating whether the high-purity ethyl ester of EPA (icosapent ethyl) at 4 g/day combined with statin therapy is superior to statin therapy alone for reducing CV events in high-risk patients with mixed dyslipidemia. The results from this study are expected to clarify the role of EPA as adjunctive therapy to a statin for reduction of residual CV risk. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Homology and Potential Cellular and Molecular Mechanisms for the Development of Unique Feather Morphologies in Early Birds

    PubMed Central

    O’Connor, Jingmai K.; Chiappe, Luis M.; Chuong, Cheng-ming; Bottjer, David J.; You, Hailu

    2013-01-01

    At least two lineages of Mesozoic birds are known to have possessed a distinct feather morphotype for which there is no neornithine (modern) equivalent. The early stepwise evolution of apparently modern feathers occurred within Maniraptora, basal to the avian transition, with asymmetrical pennaceous feathers suited for flight present in the most basal recognized avian, Archaeopteryx lithographica. The number of extinct primitive feather morphotypes recognized among non-avian dinosaurs continues to increase with new discoveries; some of these resemble feathers present in basal birds. As a result, feathers between phylogenetically widely separated taxa have been described as homologous. Here we examine the extinct feather morphotypes recognized within Aves and compare these structures with those found in non-avian dinosaurs. We conclude that the “rachis dominated” tail feathers of Confuciusornis sanctus and some enantiornithines are not equivalent to the “proximally ribbon-like” pennaceous feathers of the juvenile oviraptorosaur Similicaudipteryx yixianensis. Close morphological analysis of these unusual rectrices in basal birds supports the interpretation that they are modified pennaceous feathers. Because this feather morphotype is not seen in living birds, we build on current understanding of modern feather molecular morphogenesis to suggest a hypothetical molecular developmental model for the formation of the rachis dominated feathers of extinct basal birds. PMID:24003379

  16. Time-resolved cellular effects induced by TcdA from Clostridium difficile.

    PubMed

    Jochim, Nelli; Gerhard, Ralf; Just, Ingo; Pich, Andreas

    2014-05-30

    The anaerobe Clostridium difficile is a common pathogen that causes infection of the colon leading to diarrhea or pseudomembranous colitis. Its major virulence factors are toxin A (TcdA) and toxin B (TcdB), which specifically inactivate small GTPases by glucosylation leading to reorganization of the cytoskeleton and finally to cell death. In the present work a quantitative proteome analysis using the isotope-coded protein label (ICPL) approach was conducted to investigate proteome changes in the colon cell line Caco-2 after treatment with recombinant wild-type TcdA (rTcdA-wt) or a glucosyltransferase-deficient mutant TcdA (rTcdA-mut). Proteins from crude cell lysates or cellular subfractions were identified by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS). Two time points (5 h, 24 h) of toxin treatment were analyzed and about 4000 proteins were identified in each case. After 5 h treatment with rTcdA-wt, 150 proteins had a significantly altered abundance; rTcdA-mut caused regulation of 50 proteins at this time point. After 24 h treatment with rTcdA-wt changes in abundance of 61 proteins were observed, but no changes in protein abundance were detected after 24 h if cells were treated with rTcdA-mut. TcdA affected several proteins involved in signaling events, cytoskeleton and cell-cell contact organization, translation, and metabolic processes. The ICPL-dependent quantification was verified by label-free targeted MS techniques based on multiple reaction monitoring (MRM) and triple quadrupole mass spectrometry. LC/MS-based proteome analyses and the ICPL approach revealed comprehensive and reproducible proteome date and provided new insights into the cellular effects of clostridial glucosylating toxins (CGT). Copyright © 2014 John Wiley & Sons, Ltd.

  17. Effects of acute and chronic methamphetamine administration on cynomolgus monkey hippocampus structure and cellular transcriptome.

    PubMed

    Choi, Mi Ran; Chun, Ji-Won; Kwak, Su Min; Bang, Sol Hee; Jin, Yeung-Bae; Lee, Youngjeon; Kim, Han-Na; Chang, Kyu-Tae; Chai, Young Gyu; Lee, Sang-Rae; Kim, Dai-Jin

    2018-05-23

    Methamphetamine (MA), a psychostimulant abused worldwide, gives rise to neurotoxicity in the hippocampus, resulting in cognitive impairments and hippocampal volume reduction. The cellular and molecular mechanisms associated with hippocampal impairments due to MA remain unknown. The aim of this study was to investigate the effects of MA on structural alterations and gene expressions in the hippocampus. We analyzed the pattern of volumetric changes in the hippocampus using magnetic resonance imaging (MRI) after acute and chronic administration of MA to cynomolgus macaques. In addition, we performed large-scale transcriptome profiling in the hippocampus using RNA-Seq technology. The hippocampus in response to acute and chronic MA exhibited a significant volumetric atrophy compared with the hippocampus of controls. The genes associated with cytoskeleton organization and phagocytosis were downregulated in the acute MA-treated group compared to the control group. On the other hand, genes associated with synaptic transmission, regulation of neuron differentiation and regulation of neurogenesis were downregulated in the chronic MA-treated group. We confirmed that expression patterns for ADM, BMP4, CHRD, PDYN, UBA1, profilin 2 (PFN2), ENO2 and NSE mRNAs were similar to the results from RNA-Seq based on quantitative RT-PCR. In particular, PFN2 mRNA and protein expression levels, which play important roles in actin cytoskeleton dynamics, were decreased by acute and chronic MA administration. These results not only aid the understanding of cellular and molecular mechanisms regulated by MA in the hippocampus but also suggest basic information aiding biomarker and novel drug development for treating hippocampal impairment caused by MA abuse. Copyright © 2017. Published by Elsevier Inc.

  18. Vibroacoustic disease: biological effects of infrasound and low-frequency noise explained by mechanotransduction cellular signalling.

    PubMed

    Alves-Pereira, Mariana; Castelo Branco, Nuno A A

    2007-01-01

    At present, infrasound (0-20 Hz) and low-frequency noise (20-500 Hz) (ILFN, 0-500 Hz) are agents of disease that go unchecked. Vibroacoustic disease (VAD) is a whole-body pathology that develops in individuals excessively exposed to ILFN. VAD has been diagnosed within several professional groups employed within the aeronautical industry, and in other heavy industries. However, given the ubiquitous nature of ILFN and the absence of legislation concerning ILFN, VAD is increasingly being diagnosed among members of the general population, including children. VAD is associated with the abnormal growth of extra-cellular matrices (collagen and elastin), in the absence of an inflammatory process. In VAD, the end-product of collagen and elastin growth is reinforcement of structural integrity. This is seen in blood vessels, cardiac structures, trachea, lung, and kidney of both VAD patients and ILFN-exposed animals. VAD is, essentially, a mechanotransduction disease. Inter- and intra-cellular communication is achieved through both biochemical and mechanotranduction signalling. When the structural components of tissue are altered, as is seen in ILFN-exposed specimens, the mechanically mediated signalling is, at best, impaired. Common medical diagnostic tests, such as EKG, EEG, as well as many blood chemistry analyses, are based on the mal-function of biochemical signalling processes. VAD patients typically present normal values for these tests. However, when echocardiography, brain MRI or histological studies are performed, where structural changes can be identified, all consistently show significant changes in VAD patients and ILFN-exposed animals. Frequency-specific effects are not yet known, valid dose-responses have been difficult to identify, and large-scale epidemiological studies are still lacking.

  19. Molecular and cellular effects of azilsartan: a new generation angiotensin II receptor blocker.

    PubMed

    Kajiya, Takashi; Ho, Christopher; Wang, Jiaming; Vilardi, Ryan; Kurtz, Theodore W

    2011-12-01

    Azilsartan medoxomil is a newly approved angiotensin receptor blocker (ARB) reported to lower 24-h blood pressure more effectively than maximally recommended doses of older ARBs. Although azilsartan is considered to be an unusually potent angiotensin II type 1 (AT1) receptor antagonist, little is known about the potential pleiotropic effects of this molecule. We investigated pleiotropic features of azilsartan in cell-based assay systems independent of its effects on blood pressure. In cultured 3T3-L1 preadipocytes, azilsartan enhanced adipogenesis and exerted greater effects than valsartan on expression of genes encoding peroxisome proliferator-activated receptor-α (PPARα), PPARδ, leptin, adipsin, and adiponectin. The effects of azilsartan on adipocyte differentiation and gene expression were observed at concentrations of azilsartan that did not classically stimulate PPAR activity in cell-based transactivation assays. Azilsartan also potently inhibited vascular cell proliferation in the absence of exogenously supplemented angiotensin II. In aortic endothelial cells, azilsartan inhibited cell proliferation at concentrations as low as 1 μmol/l, whereas valsartan showed little or no antiproliferative effects at concentrations below 10 μmol/l. Antiproliferative effects of azilsartan were also observed in cells lacking AT1 receptors. In addition, azilsartan, but not valsartan, blocked angiotensin II-induced activation of mitogen-activated protein kinase in vascular smooth muscle cells 4-8 h after washout of drug from the incubation media. These findings suggest that azilsartan can function as a pleiotropic ARB with potentially beneficial effects on cellular mechanisms of cardiometabolic disease through actions that could involve more than just blockade of AT1 receptors and/or reduction in blood pressure.

  20. Comparative studies on cellular behaviour of carnation (Dianthus caryophyllus Linn. cv. Grenadin) grown in vivo and in vitro for early detection of somaclonal variation.

    PubMed

    Yaacob, Jamilah Syafawati; Taha, Rosna Mat; Khorasani Esmaeili, Arash

    2013-01-01

    The present study deals with the cytological investigations on the meristematic root cells of carnation (Dianthus caryophyllus Linn.) grown in vivo and in vitro. Cellular parameters including the mitotic index (MI), chromosome count, ploidy level (nuclear DNA content), mean cell and nuclear areas, and cell doubling time (Cdt) were determined from the 2 mm root tip segments of this species. The MI value decreased when cells were transferred from in vivo to in vitro conditions, perhaps due to early adaptations of the cells to the in vitro environment. The mean chromosome number was generally stable (2n = 2x = 30) throughout the 6-month culture period, indicating no occurrence of early somaclonal variation. Following the transfer to the in vitro environment, a significant increase was recorded for mean cell and nuclear areas, from 26.59 ± 0.09  μm² to 35.66 ± 0.10  μm² and 142.90 ± 0.59  μm² to 165.05 ± 0.58  μm², respectively. However, the mean cell and nuclear areas of in vitro grown D. caryophyllus were unstable and fluctuated throughout the tissue culture period, possibly due to organogenesis or rhizogenesis. Ploidy level analysis revealed that D. caryophyllus root cells contained high percentage of polyploid cells when grown in vivo and maintained high throughout the 6-month culture period.

  1. Comparative Studies on Cellular Behaviour of Carnation (Dianthus caryophyllus Linn. cv. Grenadin) Grown In Vivo and In Vitro for Early Detection of Somaclonal Variation

    PubMed Central

    Yaacob, Jamilah Syafawati; Taha, Rosna Mat; Khorasani Esmaeili, Arash

    2013-01-01

    The present study deals with the cytological investigations on the meristematic root cells of carnation (Dianthus caryophyllus Linn.) grown in vivo and in vitro. Cellular parameters including the mitotic index (MI), chromosome count, ploidy level (nuclear DNA content), mean cell and nuclear areas, and cell doubling time (Cdt) were determined from the 2 mm root tip segments of this species. The MI value decreased when cells were transferred from in vivo to in vitro conditions, perhaps due to early adaptations of the cells to the in vitro environment. The mean chromosome number was generally stable (2n = 2x = 30) throughout the 6-month culture period, indicating no occurrence of early somaclonal variation. Following the transfer to the in vitro environment, a significant increase was recorded for mean cell and nuclear areas, from 26.59 ± 0.09 μm2 to 35.66 ± 0.10 μm2 and 142.90 ± 0.59 μm2 to 165.05 ± 0.58 μm2, respectively. However, the mean cell and nuclear areas of in vitro grown D. caryophyllus were unstable and fluctuated throughout the tissue culture period, possibly due to organogenesis or rhizogenesis. Ploidy level analysis revealed that D. caryophyllus root cells contained high percentage of polyploid cells when grown in vivo and maintained high throughout the 6-month culture period. PMID:23766703

  2. Effect of crystals and fibrous network polymer additives on cellular morphology of microcellular foams

    NASA Astrophysics Data System (ADS)

    Miyamoto, Ryoma; Utano, Tatsumi; Yasuhara, Shunya; Ishihara, Shota; Ohshima, Masahiro

    2015-05-01

    In this study, the core-back foam injection molding was used for preparing microcelluar polypropylene (PP) foam with either a 1,3:2,4 bis-O-(4-methylbenzylidene)-D-sorbitol gelling agent (Gel-all MD) or a fibros network polymer additive (Metablen 3000). Both agent and addiive could effectively control the celluar morphology in foams but somehow different ways. In course of cooling the polymer with Gel-all MD in the mold caity, the agent enhanced the crystal nucleation and resulted in the large number of small crystals. The crystals acted as effective bubble nucleation agent in foaming process. Thus, the agent reduced the cell size and increased the cell density, drastically. Furthermore, the small crystals provided an inhomogenuity to the expanding cell wall and produced the high open cell content with nano-scale fibril structure. Gell-all as well as Metablene 3000 formed a gel-like fibrous network in melt. The network increased the elongational viscosity and tended to prevent the cell wall from breaking up. The foaming temperature window was widened by the presence of the network. Especially, the temperature window where the macro-fibrous structure was formed was expanded to the higher temperature. The effects of crystal nucleating agent and PTFE on crystals' size and number, viscoelsticity, rheological propreties of PP and cellular morphology were compared and thorougly investigated.

  3. Different cellular effects of four anti-inflammatory eye drops on human corneal epithelial cells: independent in active components.

    PubMed

    Qu, Mingli; Wang, Yao; Yang, Lingling; Zhou, Qingjun

    2011-01-01

    To evaluate and compare the cellular effects of four commercially available anti-inflammatory eye drops and their active components on human corneal epithelial cells (HCECs) in vitro. The cellular effects of four eye drops (Bromfenac Sodium Hydrate Eye Drops, Pranoprofen Eye Drops, Diclofenac Sodium Eye Drops, and Tobramycin & Dex Eye Drops) and their corresponding active components were evaluated in an HCEC line with five in vitro assays. Cell proliferation and migration were measured using 3-(4,5)-dimethylthiahiazo (-z-y1)-3 5-di-phenytetrazoliumromide (MTT) assay and transwell migration assay. Cell damage was determined with the lactate dehydrogenase (LDH) assay. Cell viability and median lethal time (LT₅₀) were measured by 7-amino-actinomycin D (7-AAD) staining and flow cytometry analysis. Cellular effects after exposure of HCECs to the four anti-inflammatory eye drops were concentration dependent. The differences of cellular toxicity on cell proliferation became significant at lower concentrations (<0.002%). Diclofenac Sodium Eye Drops showed significant increasing effects on cell damage and viability when compared with the other three solutions. Tobramycin & Dex Eye Drops inhibited the migration of HCECs significantly. Tobramycin & Dex Eye Drops showed the quickest effect on cell viability: the LT₅₀ was 3.28, 9.23, 10.38, and 23.80 min for Tobramycin & Dex Eye Drops, Diclofenac Sodium Eye Drops, Pranoprofen Eye Drops, and Bromfenac Sodium Hydrate Eye Drops, respectively. However, the comparisons of cellular toxicity revealed significant differences between the eye drops and their active components under the same concentration. The corneal epithelial toxicity differences among the active components of the four eye drops became significant as higher concentration (>0.020%). The four anti-inflammatory eye drops showed different cellular effects on HCECs, and the toxicity was not related with their active components, which provides new reference for the

  4. An attempt of modelling debris flows characterised by strong inertial effects through Cellular Automata

    NASA Astrophysics Data System (ADS)

    Iovine, G.; D'Ambrosio, D.

    2003-04-01

    Cellular Automata models do represent a valid method for the simulation of complex phenomena, when these latter can be described in "a-centric" terms - i.e. through local interactions within a discrete time-space. In particular, flow-type landslides (such as debris flows) can be viewed as a-centric dynamical system. SCIDDICA S4b, the last release of a family of two-dimensional hexagonal Cellular Automata models, has recently been developed for simulating debris flows characterised by strong inertial effects. It has been derived by progressively enriching an initial simplified CA model, originally derived for simulating very simple cases of slow-moving flow-type landslides. In S4b, by applying an empirical strategy, the inertial characters of the flowing mass have been translated into CA terms. In the transition function of the model, the distribution of landslide debris among the cells is computed by considering the momentum of the debris which move among the cells of the neighbourhood, and privileging the flow direction. By properly setting the value of one of the global parameters of the model (the "inertial factor"), the mechanism of distribution of the landslide debris among the cells can be influenced in order to emphasise the inertial effects, according to the energy of the flowing mass. Moreover, the high complexity of both the model and of the phenomena to be simulated (e.g. debris flows characterised by severe erosion along their path, and by strong inertial effects) suggested to employ an automated technique of evaluation, for the determination of the best set of global parameters. Accordingly, the calibration of the model has been performed through Genetic Algorithms, by considering several real cases of study: these latter have been selected among the population of landslides triggered in Campania (Southern Italy) in May 1998 and December 1999. Obtained results are satisfying: errors computed by comparing the simulations with the map of the real

  5. [Cellular and molecular effects of the antidepressant hyperforin on brain cells: Review of the literature].

    PubMed

    Bouron, A; Lorrain, E

    2014-04-01

    pharmacological tool to investigate the functions of endogenous TRPC6 channels in various cell types. Chronically applied to neuronal cell line PC12, hyperforin promotes the extension of neurites via a mechanism implying TRPC6 channels. It is also known to trigger an intracellular signalling pathway that involves the cAMP-dependent protein kinase A and the transcription factor cyclic adenosine monophosphate response element binding protein (CREB). This leads to an up-regulation of the expression of the brain-derived neurotrophic factor (BDNF) receptor neurotrophic tyrosine kinase (TrkB) and TRPC6. This hyperforin-dependent cascade is controlled by Ca(2+) ions and occurs specifically in the cortex but not in the hippocampus. One key aspect of the cellular responses induced by hyperforin is its impact on the homeostasis of several cations (Na(+), Ca(2+), Zn(2+) and H(+)). In vitro experiments demonstrated that hyperforin, which changes the fluidity of membranes, elevates the intracellular concentration of these elements by promoting their influx and/or their release from internal compartments. The phloroglucinol derivative hyperforin is an important bioactive molecule of Hypericum perforatum exhibiting antidepressive properties. Although it inhibits the reuptake of many neurotransmitters, hyperforin is in fact a multi-target drug influencing the cellular homeostatic mechanisms of Ca(2+), Zn(2+), H(+) and Na(+) due to its effects on their influx and/or release from internal stores. In addition, hyperforin is a potent modulator of mitochondrial functions. In spite of recent progress in the characterization of the cellular hyperforin responses, it remains unclear what pharmacological aspects of hyperforin functions are relevant in vivo. Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  6. A cellular automata model for avascular solid tumor growth under the effect of therapy

    NASA Astrophysics Data System (ADS)

    Reis, E. A.; Santos, L. B. L.; Pinho, S. T. R.

    2009-04-01

    Tumor growth has long been a target of investigation within the context of mathematical and computer modeling. The objective of this study is to propose and analyze a two-dimensional stochastic cellular automata model to describe avascular solid tumor growth, taking into account both the competition between cancer cells and normal cells for nutrients and/or space and a time-dependent proliferation of cancer cells. Gompertzian growth, characteristic of some tumors, is described and some of the features of the time-spatial pattern of solid tumors, such as compact morphology with irregular borders, are captured. The parameter space is studied in order to analyze the occurrence of necrosis and the response to therapy. Our findings suggest that transitions exist between necrotic and non-necrotic phases (no-therapy cases), and between the states of cure and non-cure (therapy cases). To analyze cure, the control and order parameters are, respectively, the highest probability of cancer cell proliferation and the probability of the therapeutic effect on cancer cells. With respect to patterns, it is possible to observe the inner necrotic core and the effect of the therapy destroying the tumor from its outer borders inwards.

  7. Cellular and molecular effects of nonreciprocal chromosome translocations in Saccharomyces cerevisiae

    PubMed Central

    Nikitin, Dmitri; Tosato, Valentina; Zavec, Apolonija Bedina; Bruschi, Carlo V.

    2008-01-01

    Saccharomyces cerevisiae strains harboring a nonreciprocal, bridge-induced translocation (BIT) between chromosomes VIII and XV exhibited an abnormal phenotype comprising elongated buds and multibudded, unevenly nucleated pseudohyphae. In these cells, we found evidence of molecular effects elicited by the translocation event and specific for its particular genomic location. Expression of genes flanking both translocation breakpoints increased up to five times, correlating with an increased RNA polymerase II binding to their promoters and with their histone acetylation pattern. Microarray data, CHEF, and quantitative PCR confirmed the data on the dosage of genes present on the chromosomal regions involved in the translocation, indicating that telomeric fragments were either duplicated or integrated mostly on chromosome XI. FACS analysis revealed that the majority of translocant cells were blocked in G1 phase and a few of them in G2. Some cells showed a posttranslational decrease of cyclin B1, in agreement with elongated buds diagnostic of a G2/M phase arrest. The actin1 protein was in some cases modified, possibly explaining the abnormal morphology of the cells. Together with the decrease in Rad53p and the lack of its phosphorylation, these results indicate that these cells have undergone adaptation after checkpoint-mediated G2/M arrest after chromosome translocation. These BIT translocants could serve as model systems to understand further the cellular and molecular effects of chromosome translocation and provide fundamental information on its etiology of neoplastic transformation in mammals. PMID:18599460

  8. Effects of Ionizing Radiation on Cellular Structures, Induced Instability, and Carcinogenesis

    SciTech Connect

    Resat, Marianne S.; Arthurs, Benjamin J.; Estes, Brian J.

    2006-03-01

    According to the American Cancer Society, the United States can expect 1,368,030 new cases of cancer in 2004 [1]. Among the many carcinogens Americans are exposed to, ionizing radiation will contribute to this statistic. Humans live in a radiation environment. Ionizing radiation is in the air we breathe, the earth we live on, and the food we eat. Man-made radiation adds to this naturally occurring radiation level thereby increasing the chance for human exposure. For many decades the scientific community, governmental regulatory bodies, and concerned citizens have struggled to estimate health risks associated with radiation exposures, particularly at low doses.more » While cancer induction is the primary concern and the most important somatic effect of exposure to ionizing radiation, potential health risks do not involve neoplastic diseases exclusively but also include somatic mutations that might contribute to birth defects and ocular maladies, and heritable mutations that might impact on disease risks in future generations. Consequently it is important we understand the effect of ionizingradiation on cellular structures and the subsequent long-term health risks associated with exposure to ionizing radiation.« less

  9. Effects of radiofrequency radiation emitted by cellular telephones on the cognitive functions of humans.

    PubMed

    Eliyahu, Ilan; Luria, Roy; Hareuveny, Ronen; Margaliot, Menachem; Meiran, Nachshon; Shani, Gad

    2006-02-01

    The present study examined the effects of exposure to Electromagnetic Radiation emitted by a standard GSM phone at 890 MHz on human cognitive functions. This study attempted to establish a connection between the exposure of a specific area of the brain and the cognitive functions associated with that area. A total of 36 healthy right-handed male subjects performed four distinct cognitive tasks: spatial item recognition, verbal item recognition, and two spatial compatibility tasks. Tasks were chosen according to the brain side they are assumed to activate. All subjects performed the tasks under three exposure conditions: right side, left side, and sham exposure. The phones were controlled by a base station simulator and operated at their full power. We have recorded the reaction times (RTs) and accuracy of the responses. The experiments consisted of two sections, of 1 h each, with a 5 min break in between. The tasks and the exposure regimes were counterbalanced. The results indicated that the exposure of the left side of the brain slows down the left-hand response time, in the second-later-part of the experiment. This effect was apparent in three of the four tasks, and was highly significant in only one of the tests. The exposure intensity and its duration exceeded the common exposure of cellular phone users.

  10. Effect of lycopene and {beta}-carotene on peroxynitrite-mediated cellular modifications

    SciTech Connect

    Muzandu, Kaampwe; Ishizuka, Mayumi; Sakamoto, Kentaro Q.

    2006-09-15

    Peroxynitrite formed by the reaction of superoxide and nitric oxide is a highly reactive species with a role in various pathological processes such as cancer, chronic inflammation, and cardiovascular and neurological diseases. In the present study, the effect of the carotenoids, lycopene and {beta}-carotene, on peroxynitrite-mediated modifications in plasmid DNA as well as cellular DNA and proteins were investigated. In pUC18 plasmid DNA, these carotenoids strongly inhibited DNA strand breaks caused by peroxynitrite generated from 3-morpholinosydnonimine (SIN-1). SIN-1 was also used to determine effects on DNA damage and protein tyrosine nitration in Chinese hamster lung fibroblasts. SIN-1 dose-dependently increased nitrationmore » of proteins in cells above basal levels as determined by Western blotting. This nitration was inhibited in the presence of the uric acid as well as lycopene. Physiological concentrations (0.31-10 {mu}M) of lycopene and {beta}-carotene also had protective effects on DNA damage, as measured by the comet assay. Lycopene significantly reduced DNA damage particularly, in the median range of concentrations (2.5 {mu}M). The protective effects of lycopene and {beta}-carotene could be due to their scavenging of reactive oxygen (ROS) and/or nitrogen species (RNS) as they reduce the amount of intracellular ROS/RNS produced following treatment with SIN-1 by as much as 47.5% and 42.4%, respectively. The results obtained in this study suggest that carotenoids may alleviate some of the deleterious effects of peroxynitrite and possibly other reactive nitrogen species as well in vivo.« less

  11. Cellular interface morphologies in directional solidification. II - The effect of grain boundaries

    NASA Technical Reports Server (NTRS)

    Ungar, Lyle H.; Brown, Robert A.

    1984-01-01

    A singular perturbation analysis valid for small grain-boundary slopes is used with the one-sided model for solidification to show that grain boundaries introduce imperfections into the symmetry of the developing cellular interfaces which rupture the junction between the family of planar shapes and the bifurcating cellular families. Undulating interfaces are shown to develop first near grain boundaries, and to evolve with decreasing temperature gradient either by a smooth transition from the almost planar family or by a sudden jump to moderate-amplitude cellular forms, depending on the growth rate.

  12. Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy.

    PubMed

    Li, Mi; Liu, LianQing; Xi, Ning; Wang, YueChao; Xiao, XiuBin; Zhang, WeiJing

    2015-09-01

    Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy (AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells.

  13. Early sport specialization: roots, effectiveness, risks.

    PubMed

    Malina, Robert M

    2010-01-01

    Year-round training in a single sport beginning at a relatively young age is increasingly common among youth. Contributing factors include perceptions of Eastern European sport programs, a parent's desire to give his or her child an edge, labeling youth as talented at an early age, pursuit of scholarships and professional contracts, the sporting goods and services industry, and expertise research. The factors interact with the demands of sport systems. Limiting experiences to a single sport is not the best path to elite status. Risks of early specialization include social isolation, overdependence, burnout, and perhaps risk of overuse injury. Commitment to a single sport at an early age immerses a youngster in a complex world regulated by adults, which is a setting that facilitates manipulation - social, dietary, chemical, and commercial. Youth sport must be kept in perspective. Participants, including talented young athletes, are children and adolescents with the needs of children and adolescents.

  14. Sexism and Early Parenting: Cause and Effect?

    ERIC Educational Resources Information Center

    Cusick, Theresa

    1987-01-01

    Sexism and sex role stereotyping exacerbate teen pregnancy rates in several ways. This article attempts to synthesize relevant research and uses existing research to detail the specific ways sexism abets early parenting. Several recommendations for addressing teen pregnancy issues are made. (IAH)

  15. Effects of Hypercapnia on Acute Cellular Rejection after Lung Transplantation in Rats.

    PubMed

    Tan, Jing; Liu, Yanhong; Jiang, Tao; Wang, Ling; Zhao, Can; Shen, Dongfang; Cui, Xiaoguang

    2018-01-01

    Hypercapnia alleviates pulmonary ischemia-reperfusion injury, regulates T lymphocytes, and inhibits immune reaction. This study aimed to evaluate the effect of hypercapnia on acute cellular rejection in a rat lung transplantation model. Recipient rats in sham-operated (Wistar), isograft (Wistar to Wistar), and allograft (Sprague-Dawley to Wistar) groups were ventilated with 50% oxygen, whereas rats in the hypercapnia (Sprague-Dawley to Wistar) group were administered 50% oxygen and 8% carbon dioxide for 90 min during reperfusion (n = 8). Recipients were euthanized 7 days after transplantation. The hypercapnia group showed a higher oxygenation index (413 ± 78 vs. 223 ± 24), lower wet weight-to-dry weight ratio (4.23 ± 0.54 vs. 7.04 ± 0.80), lower rejection scores (2 ± 1 vs. 4 ± 1), and lower apoptosis index (31 ± 6 vs. 57 ± 4) as compared with the allograft group. The hypercapnia group showed lower CD8 (17 ± 4 vs. 31 ± 3) and CD68 (24 ± 3 vs. 43 ± 2), lower CD8 T cells (12 ± 2 vs. 35 ± 6), and higher CD4/CD8 ratio (2.2 ± 0.6 vs. 1.1 ± 0.4) compared to the allograft group. Tumor necrosis factor-α (208 ± 40 vs. 292 ± 49), interleukin-2 (30.6 ± 6.7 vs. 52.7 ± 8.3), and interferon-γ (28.1 ± 4.9 vs. 62.7 ± 10.1) levels in the hypercapnia group were lower than those in allograft group. CD4, CD4 T cells, and interleukin-10 levels were similar between groups. Hypercapnia ameliorated acute cellular rejection in a rat lung transplantation model.

  16. A study on the effects of relativistic heavy charged particles on the cellular microenvironment

    NASA Astrophysics Data System (ADS)

    Costes, Sylvain Vincent

    This study was done under the National Aeronautics Space Administration (NASA) effort to assess the effect of cosmic radiation on astronauts during a 3 year mission to Mars. Carcinogenesis is known to be induced more efficiently by cosmic radiation. Our attention was turned towards one of the most efficient cosmic particles in inducing cancer, relativistic Fe, and focused in assessing its effect on the cellular microenvironment (ECM). Previous observations on mammary glands were showing irregularities in the immunoreactivity of the ECM protein laminin one hour after whole body irradiation with 1GeV/amu Fe ions for a dose of 0.8 Gy. This effect was not observed after 5 Gy γ-rays exposure. The rapidity of such a change suggested that the effect might be due to a physical event specific to relativistic charged particles (HZE), rather than a biological event. Our study showed that this effect is actually a complex and rapid response of the microenvironment to highly ionizing radiation. It involves a fast disruption of the basement membrane of the ECM induced by the highly localized ionization and reactive oxygen formation around the track of the Fe ion. This disruption triggers further chemical and biological responses involved in the remodeling of the laminin network in the basement membrane. A metalloproteinase is suspected to be the intermediate protease affecting laminin. The HZE effect on the microenvironment was seen in both mouse mammary glands and skin, but the laminin isoforms sensitive to Fe ions were different for each organ, with a clear disruption of laminin-1 network in skin and of laminin-5 in mammary glands. In addition, the laminin receptor integrins seem to be involved in this mechanism, but its contribution is unclear at this point. Finally, such studies suggest a shift from the concept of relative biological effectiveness (RBE) used in classical radiation biology since the effect is only seen with HZE at viable whole body doses. In addition, this

  17. Cellular Automata

    NASA Astrophysics Data System (ADS)

    Gutowitz, Howard

    1991-08-01

    Cellular automata, dynamic systems in which space and time are discrete, are yielding interesting applications in both the physical and natural sciences. The thirty four contributions in this book cover many aspects of contemporary studies on cellular automata and include reviews, research reports, and guides to recent literature and available software. Chapters cover mathematical analysis, the structure of the space of cellular automata, learning rules with specified properties: cellular automata in biology, physics, chemistry, and computation theory; and generalizations of cellular automata in neural nets, Boolean nets, and coupled map lattices. Current work on cellular automata may be viewed as revolving around two central and closely related problems: the forward problem and the inverse problem. The forward problem concerns the description of properties of given cellular automata. Properties considered include reversibility, invariants, criticality, fractal dimension, and computational power. The role of cellular automata in computation theory is seen as a particularly exciting venue for exploring parallel computers as theoretical and practical tools in mathematical physics. The inverse problem, an area of study gaining prominence particularly in the natural sciences, involves designing rules that possess specified properties or perform specified task. A long-term goal is to develop a set of techniques that can find a rule or set of rules that can reproduce quantitative observations of a physical system. Studies of the inverse problem take up the organization and structure of the set of automata, in particular the parameterization of the space of cellular automata. Optimization and learning techniques, like the genetic algorithm and adaptive stochastic cellular automata are applied to find cellular automaton rules that model such physical phenomena as crystal growth or perform such adaptive-learning tasks as balancing an inverted pole. Howard Gutowitz is

  18. The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects.

    PubMed

    Sadeghi, Akram; Hami, Javad; Razavi, Shahnaz; Esfandiary, Ebrahim; Hejazi, Zahra

    2016-01-01

    Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus. The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms. Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes. Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals.

  19. [The effect of Echinacea angustifolia on non-specific cellular immunity in the mouse].

    PubMed

    Schumacher, A; Friedberg, K D

    1991-02-01

    Echinacea belongs to the most usable plants in medical treatment since many years. It is applicable in the fields of homoepathy and allopathy, however, there are many different ways of treatment. Two species are listed in the European Pharmacopoea: Echinacea angustifolia and Echinacea purpurea. They differ in morphology and their chemical composition. There have been chemical and biological analyses of Echinacea for about 80 years. After exact investigations of these reports, the following result were found: Most chemical analyses were done with Echinacea angustifolia, especially the older ones, whereas biological activity was tested with Echinacea purpurea. In almost all of these experiments, proprietaries were preferred to use in contrast to any plant extracts. Most of the reports, which declared the stimulating biological activity of Echinacea could not resist any critical opinion. So the frequency of medical application of this drug is mainly due to delivered practical knowledge. The experiments described in this study were practised with a water-soluble plant extract of Echinacea angustifolia. Echinacosid one of its low-molecular compounds and proprietaries which contains this plant. Their influence on the unspecified cellular immunity of the mouse after intraperitoneal, intravenous or peroral application was investigated. Under various conditions no effects on the immuno system could be found using the carbon clearance test.

  20. Expression of Histone Deacetylases in Cellular Compartments of the Mouse Brain and the Effects of Ischemia

    PubMed Central

    Bachleda, Amelia; Morrison, Richard S.; Murphy, Sean P.

    2011-01-01

    Drugs that inhibit specific histone deacetylase (HDAC) activities have enormous potential in preventing the consequences of acute injury to the nervous system and in allaying neurodegeneration. However, very little is known about the expression pattern of the HDACs in the central nervous system (CNS). Identifying the cell types that express HDACs in the CNS is important for determining therapeutic targets for HDAC inhibitors and evaluating potential side effects. We characterized the cellular expression of HDACs 1–3, and HDACs 4 and 6, in the adult mouse brain in the cingulate cortex, parietal cortex, dentate gyrus, and CA1 regions of the hippocampus and subcortical white matter. Expression of class I HDACs showed a cell-and region-specific pattern. Transient focal ischemia induced by temporary middle cerebral artery occlusion, or global ischemia induced by in vitro oxygen–glucose deprivation, altered the extent of HDAC expression in a region- and cell-specific manner. The pan-HDAC inhibitor, SAHA, reduced ischemia-induced alterations in HDACs. The results suggest that in addition to promoting epigenetic changes in transcriptional activity in the nucleus of neurons and glia, HDACs may also have non-transcriptional actions in axons and the distant processes of glial cells and may significantly modulate the response to injury in a cell- and region-specific manner. PMID:21966324

  1. Restoring Effects of Natural Anti-Oxidant Quercetin on Cellular Senescent Human Dermal Fibroblasts.

    PubMed

    Sohn, Eun-Ju; Kim, Jung Min; Kang, Se-Hui; Kwon, Joseph; An, Hyun Joo; Sung, Jung-Suk; Cho, Kyung A; Jang, Ik-Soon; Choi, Jong-Soon

    2018-05-08

    The oxidative damage initiated by reactive oxygen species (ROS) is a major contributor to the functional decline and disability that characterizes aging. The anti-oxidant flavonoid, quercetin, is a plant polyphenol that may be beneficial for retarding the aging process. We examined the restoring properties of quercetin on human dermal fibroblasts (HDFs). Quercetin directly reduced either intracellular or extracellular ROS levels in aged HDFs. To find the aging-related target genes by quercetin, microarray analysis was performed and two up-regulated genes LPL and KCNE2 were identified. Silencing LPL increased the expression levels of senescence proteins such as p16 INK4A and p53 and silencing KCNE2 reversed gene expressions of EGR1 and p-ERK in quercetin-treated aged HDFs. Silencing of LPL and KCNE2 decreased the expression levels of antioxidant enzymes such as superoxide dismutase and catalase. Also, the mitochondrial dysfunction in aged HDFs was ameliorated by quercetin treatment. Taken together, these results suggest that quercetin has restoring effect on the cellular senescence by down-regulation of senescence activities and up-regulation of the gene expressions of anti-oxidant enzymes in aged HDFs.

  2. Effects of surface chemistry on the optical properties and cellular interaction of lanthanide-based nanoparticles

    NASA Astrophysics Data System (ADS)

    Pedraza, Francisco J.; Avalos, Julio C.; Mimun, Lawrence C.; Yust, Brian G.; Tsin, Andrew; Sardar, Dhiraj K.

    2015-03-01

    Fluorescent nanoparticles (NPs) such as KYb2F7:Tm3+ potential in biomedical applications due to their ability to absorb and emit within the biological window, where near infrared light is less attenuated by soft tissue. This results in less tissue damage and deeper tissue penetration making it a viable candidate in biological imaging. Another big factor in determining their ability to perform in a biological setting is the surface chemistry. Biocompatible coatings, including polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), pluronic and folic acid are commonly used because they pose several advantages such as ease of functionalization, better dispersion, and higher cellular uptake. To study the effects of the NP surface chemistry, KYb2F7:Tm3+ a solvothermal method using PEG, PVP, pluronic acid, and folic acid as a capping agent, followed by thorough optical characterizations. Optical changes were thoroughly studied and compared using absorption, emission, and quantum yield data. Cell viability was obtained by treating Rhesus Monkey Retinal Endothelial cells (RhREC) with KYb2F7:Tm3+ and counting viable cells following a 24 hour uptake period. The work presented will compare the optical properties and toxicity dependency on the surface chemistry on KYb2F7:Tm3+. The results will also indicate that KYb2F7:Tm3+ nanoparticles are viable candidates for various biomedical applications.

  3. The effect of the methanol extract of Galium mite on the cellular immunity and antibody synthesis.

    PubMed

    Amirghofran, Zahra; Javidnia, Katayoun; Bahmani, Masood; Azadmehr, Abbas; Esmaeilbeig, Maryam

    2011-01-01

    In the present study, the immunomodulatory effects of Galium mite, a native herb used for the treatment of inflammation in Iranian traditional medicine, was investigated. The methanolic extract of the plant was prepared and examined for in vivo cell-mediated and humoral immunity against antigen in mice. Galium mite stimulated delayed type hypersensitivity at lower concentrations and inhibited the reaction at higher ones (p < 0.05). A dose-related decrease in primary and secondary antibody titer was observed in mice treated with the extract (p < 0.006). The extract at higher concentrations significantly reduced the proliferation of human-activated lymphocytes (p < 0.001). Cell cycle analysis on human lymphocytes treated with the extract showed an increase in the number of cells in sub-G1 region, indicating the ability of the extract to induce apoptosis in these cells. Induction of apoptosis was confirmed by DNA laddering on gel electrophoresis. In conclusion, G. mite has the ability to modulate cellular and humoral immune responses to the antigenic challenge and affect the rate of cell proliferation due to induction of apoptosis in the lymphocytes.

  4. Effect of dispersants of multi-walled carbon nanotubes on cellular uptake and biological responses

    PubMed Central

    Haniu, Hisao; Saito, Naoto; Matsuda, Yoshikazu; Kim, Yoong-Ahm; Park, Ki Chul; Tsukahara, Tamotsu; Usui, Yuki; Aoki, Kaoru; Shimizu, Masayuki; Ogihara, Nobuhide; Hara, Kazuo; Takanashi, Seiji; Okamoto, Masanori; Ishigaki, Norio; Nakamura, Koichi; Kato, Hiroyuki

    2011-01-01

    Although there have been many reports about the cytotoxicity of multi-walled carbon nanotubes (MWCNTs), the results are still controversial. To investigate one possible reason, the authors investigated the influence of MWCNT dispersants on cellular uptake and cytotoxicity. Cytotoxicity was examined (measured by alamarBlue® assay), as well as intracellular MWCNT concentration and cytokine secretion (measured by flow cytometry) in human bronchial epithelial cells (BEAS-2B) exposed to a type of highly purified MWCNT vapor grown carbon fiber (VGCF®, Shōwa Denkō Kabushiki-gaisha, Tokyo, Japan) in three different dispersants (gelatin, carboxylmethyl cellulose, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine). The authors also researched the relationship between the intracellular concentration of MWCNTs and cytotoxicity by using two cell lines, BEAS-2B and MESO-1 human malignant pleural mesothelioma cells. The intracellular concentration of VGCF was different for each of the three dispersants, and the levels of cytotoxicity and inflammatory response were correlated with the intracellular concentration of VGCF. A relationship between the intracellular concentration of VGCF and cytotoxic effects was observed in both cell lines. The results indicate that dispersants affect VGCF uptake into cells and that cytotoxicity depends on the intracellular concentration of VGCF, not on the exposed dosage. Thus, toxicity appears to depend on exposure time, even at low VGCF concentrations, because VGCF is biopersistent. PMID:22228997

  5. Impact of photocatalysis on fungal cells: depiction of cellular and molecular effects on Saccharomyces cerevisiae.

    PubMed

    Thabet, Sana; Simonet, France; Lemaire, Marc; Guillard, Chantal; Cotton, Pascale

    2014-12-01

    We have investigated the antimicrobial effects of photocatalysis on the yeast model Saccharomyces cerevisiae. To accurately study the antimicrobial mechanisms of the photocatalytic process, we focused our investigations on two questions: the entry of the nanoparticles in treated cells and the fate of the intracellular environment. Transmission electronic microscopy did not reveal any entry of nanoparticles within the cells, even for long exposure times, despite degradation of the cell wall space and deconstruction of cellular compartments. In contrast to proteins located at the periphery of the cells, intracellular proteins did not disappear uniformly. Disappearance or persistence of proteins from the pool of oxidized intracellular isoforms was not correlated to their functions. Altogether, our data suggested that photocatalysis induces the establishment of an intracellular oxidative environment. This hypothesis was sustained by the detection of an increased level of superoxide ions (O2°(-)) in treated cells and by greater cell cultivability for cells expressing oxidant stress response genes during photocatalytic exposure. The increase in intracellular ROS, which was not connected to the entry of nanoparticles within the cells or to a direct contact with the plasma membrane, could be the result of an imbalance in redox status amplified by chain reactions. Moreover, we expanded our study to other yeast and filamentous fungi and pointed out that, in contrast to the laboratory model S. cerevisiae, some environmental strains are very resistant to photocatalysis. This could be related to the cell wall composition and structure. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Effect of Phospholipidosis on the Cellular Pharmacokinetics of ChloroquineS⃞

    PubMed Central

    Zheng, Nan; Zhang, Xinyuan

    2011-01-01

    In vivo, the weakly basic, lipophilic drug chloroquine (CQ) accumulates in the kidney to concentrations more than a thousand-fold greater than those in plasma. To study the cellular pharmacokinetics of chloroquine in cells derived from the distal tubule, Madin-Darby canine kidney cells were incubated with CQ under various conditions. CQ progressively accumulated without exhibiting steady-state behavior. Experiments failed to yield evidence that known active transport mechanisms mediated CQ uptake at the plasma membrane. CQ induced a phospholipidosis-like phenotype, characterized by the appearance of numerous multivesicular and multilamellar bodies (MLBs/MVBs) within the lumen of expanded cytoplasmic vesicles. Other induced phenotypic changes including changes in the volume and pH of acidic organelles were measured, and the integrated effects of all these changes were computationally modeled to establish their impact on intracellular CQ mass accumulation. Based on the passive transport behavior of CQ, the measured phenotypic changes fully accounted for the continuous, nonsteady-state CQ accumulation kinetics. Consistent with the simulation results, Raman confocal microscopy of live cells confirmed that CQ became highly concentrated within induced, expanded cytoplasmic vesicles that contained multiple MLBs/MVBs. Progressive CQ accumulation was increased by sucrose, a compound that stimulated the phospholipidosis-like phenotype, and was decreased by bafilomycin A1, a compound that inhibited this phenotype. Thus, phospholipidosis-associated changes in organelle structure and intracellular membrane content can exert a major influence on the local bioaccumulation and biodistribution of drugs. PMID:21156819

  7. Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice

    PubMed Central

    Moreno, José L.; Holloway, Terrell; Umali, Adrienne; Rayannavar, Vinayak; Sealfon, Stuart C.

    2013-01-01

    Rationale In schizophrenia patients, optimal treatment with antipsychotics requires weeks to months of sustained drug therapy. However, single administration of antipsychotic drugs can reverse schizophrenia-like behavioral alterations in rodent models of psychosis. This raises questions about the physiological relevance of such antipsychotic-like activity. Objective This study evaluates the effects of chronic treatment with clozapine on the cellular and behavioral responses induced by the hallucinogenic serotonin 5-HT2A receptor agonist lysergic acid diethylamide (LSD) as a mouse model of psychosis. Method Mice were treated chronically (21 days) with 25 mg/kg/day clozapine. Experiments were conducted 1, 7, 14, and 21 days after the last clozapine administration. [3H]Ketanserin binding and 5-HT2A mRNA expression were determined in mouse somatosensory cortex. Head-twitch behavior, expression of c-fos, which is induced by all 5-HT2A agonists, and expression of egr-1 and egr-2, which are LSD-like specific, were assayed. Results Head-twitch response was decreased and [3H]ketanserin binding was downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT2A mRNA was reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, was rescued 7 days after chronic clozapine. These effects were not observed after short treatment (2 days) with clozapine or chronic haloperidol (1 mg/kg/day). Conclusion Our findings provide a murine model of chronic atypical antipsychotic drug action and suggest downregulation of the 5-HT2A receptor as a potential mechanism involved in these persistent therapeutic-like effects. PMID:22842765

  8. Effects of mastic gum Pistacia lentiscus var. Chia on innate cellular immune effectors.

    PubMed

    Kottakis, Filippos; Kouzi-Koliakou, Kokona; Pendas, Stefanos; Kountouras, Jannis; Choli-Papadopoulou, Theodora

    2009-02-01

    The essential oil and Chios mastic gum (CMG) are natural antimicrobial agents currently broadly used in medicine owing to their antimicrobial, antioxidant, and hepatoprotective properties. The aim of this study was to investigate the effect of CMG-extracted arabinogalactan proteins (AGPs/CMG) both in vitro and in vivo, under the presence of Helicobacter pylori neutrophil-activating protein (HP-NAP), on the innate cellular immune effectors (neutrophils activations) comparing H. pylori-infected patients and healthy controls. The in-vivo effect of AGPs/CMG under the presence of HP-NAP in neutrophil activation was investigated in five H. pylori-infected patients and three healthy volunteers who received 1 g daily consumption of CMG for 2 months. All participants did not receive any immunosuppressive medication before or during the trial; patients with infectious diseases that could modify their immunologic status were excluded. In-vitro studies with pull-down experiments to assess the effect of AGPs/CMG under the presence of HP-NAP on the neutrophil activation were also carried out. Neutrophil activation was estimated by nicotinamide adenine dinucleotide phosphate-oxidase assays and optical microscopy methods by measurement of cytochrome C reduction. Neutrophil activation was reduced when incubated in vitro with HP-NAP (P=0.0027) and AGP plus HP-NAP (P=0.0004) in H. pylori-positive patients who consumed AGP for 2 months. Similar results were also obtained when neutrophils were incubated with AGP plus HP-NAP (P=0.0038) in controls. Pull-down experiments showed a specific binding of AGPs to two membrane proteins of neutrophils, possibly suggesting inhibition of neutrophil activation. AGPs/CMG inhibit neutrophil activation in the presence of HP-NAP, playing a crucial role in H. pylori-associated pathologies in gastric mucosa.

  9. Effects of fexofenadine and hydroxyzine on brake reaction time during car-driving with cellular phone use.

    PubMed

    Tashiro, Manabu; Horikawa, Etsuo; Mochizuki, Hideki; Sakurada, Yumiko; Kato, Motohisa; Inokuchi, Takatoshi; Ridout, Fran; Hindmarch, Ian; Yanai, Kazuhiko

    2005-10-01

    Antihistamines are a mainstay treatment for allergic rhinitis; however, many older agents cause adverse events, including sedation and central nervous system (CNS) impairment. Research has shown sedating effects of antihistamines on driving; currently, no known study has examined whether cellular phone usage while driving further compounds impairment in individuals administered antihistamines. The aim of this study was to examine this endpoint. In a randomized, double-blind, placebo-controlled, three-way crossover study, healthy volunteers received fexofenadine HCl 120 mg, hydroxyzine HCl 30 mg and placebo. Brake reaction time (BRT) was used to examine driving performance across four conditions: driving only; driving while completing simple calculations; complex calculations; and conversing on a cellular phone. Subjective sedation assessments were also conducted. Brake reaction time with and without cellular phone usage in fexofenadine-treated subjects did not differ significantly from placebo in any condition. In contrast, hydroxyzine-treated subjects were significantly more sedated and had slower BRTs, suggesting slower hazard recognition and brake application, compared with the fexofenadine and placebo groups in all conditions. Importantly, cellular phone operation was an additive factor, increasing BRTs in hydroxyzine-treated volunteers. Fexofenadine did not impair CNS function in subjects involved in a divided attention task of driving and cellular phone operation. Copyright (c) 2005 John Wiley & Sons, Ltd.

  10. Impaired cellular immune response to tetanus toxoid but not to cytomegalovirus in effectively HAART-treated HIV-infected children.

    PubMed

    Alsina, Laia; Noguera-Julian, Antoni; Fortuny, Clàudia

    2013-05-07

    Despite of highly active antiretroviral therapy, the response to vaccines in HIV-infected children is poor and short-lived, probably due to a defect in cellular immune responses. We compared the cellular immune response (assessed in terms of IFN-γ production) to tetanus toxoid and to cytomegalovirus in a series of 13 HIV-perinatally-infected children and adolescents with optimal immunovirological response to first line antiretroviral therapy, implemented during chronic infection. A stronger cellular response to cytomegalovirus (11 out of 13 patients) was observed, as compared to tetanus toxoid (1 out of 13; p=0.003). These results suggest that the repeated exposition to CMV, as opposed to the past exposition to TT, is able to maintain an effective antigen-specific immune response in stable HIV-infected pediatric patients and strengthen current recommendations on immunization practices in these children. Copyright © 2013. Published by Elsevier Ltd.

  11. Early Archean (approximately 3.4 Ga) prokaryotic filaments from cherts of the apex basalt, Western Australia: The oldest cellularly preserved microfossils now known

    NASA Technical Reports Server (NTRS)

    Schopf, J. W.

    1991-01-01

    In comparison with that known from later geologic time, the Archean fossil record is miniscule: although literally hundreds of Proterozoic formations, containing more that 2800 occurrences of bona fide microfossils are now known, fewer than 30 units containing some 43 categories of putative microfossils (the vast majority of which are of questionable authenticity) have been reported from the Archean. Among the oldest known fossils are Early Archean filaments reported from cherts of the Towers Formation and the Apex Basalt of the 3.3-3.6 Ga-old Warrawoona Group of Western Australia. The paleobiologic significance of the Towers Formation microstructures is open to question: thin aggregated filaments are properly regarded as dubiomicrofossils (perhaps biogenic, but perhaps not); therefore, they cannot be regarded as firm evidence of Archean life. Although authentic, filamentous microfossiles were reported from a second Towers Formation locality, because the precise layer containing the fossiliferous cherts was not relocated, this discovery can neither be reconfirmed by the original collector nor confirmed independently by other investigators. Discovery of microfossils in bedded cherts of the Apex Basalt, the stratigraphic unit immediately overlying the Towers Formation, obviates the difficulties stored above. The cellularly preserved filaments of the Apex Basalt meet all of the criteria required of a bona fide Archean microfossils. Recent studies indicate that the Apex assemblage includes at least six morphotypes of uniseriate filaments, composed of barrel-shaped, discoidal, or quadrate cells and exhibiting rounded or conical terminal cells and medial bifurcated and paired half-cells that reflect the occurrence of prokaryotic binary cell division. Interestingly, the majority of these morphotypes are morphologically more similar to extant cyanobacteria than to modern filamentous bacteria. Prokaryotes seem clearly to have been hypobradytelic, and the evidence suggests

  12. Analysis of high-throughput screening reveals the effect of surface topographies on cellular morphology.

    PubMed

    Hulsman, Marc; Hulshof, Frits; Unadkat, Hemant; Papenburg, Bernke J; Stamatialis, Dimitrios F; Truckenmüller, Roman; van Blitterswijk, Clemens; de Boer, Jan; Reinders, Marcel J T

    2015-03-01

    Surface topographies of materials considerably impact cellular behavior as they have been shown to affect cell growth, provide cell guidance, and even induce cell differentiation. Consequently, for successful application in tissue engineering, the contact interface of biomaterials needs to be optimized to induce the required cell behavior. However, a rational design of biomaterial surfaces is severely hampered because knowledge is lacking on the underlying biological mechanisms. Therefore, we previously developed a high-throughput screening device (TopoChip) that measures cell responses to large libraries of parameterized topographical material surfaces. Here, we introduce a computational analysis of high-throughput materiome data to capture the relationship between the surface topographies of materials and cellular morphology. We apply robust statistical techniques to find surface topographies that best promote a certain specified cellular response. By augmenting surface screening with data-driven modeling, we determine which properties of the surface topographies influence the morphological properties of the cells. With this information, we build models that predict the cellular response to surface topographies that have not yet been measured. We analyze cellular morphology on 2176 surfaces, and find that the surface topography significantly affects various cellular properties, including the roundness and size of the nucleus, as well as the perimeter and orientation of the cells. Our learned models capture and accurately predict these relationships and reveal a spectrum of topographies that induce various levels of cellular morphologies. Taken together, this novel approach of high-throughput screening of materials and subsequent analysis opens up possibilities for a rational design of biomaterial surfaces. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. Paradoxical Adipose Hyperplasia and Cellular Effects After Cryolipolysis: A Case Report.

    PubMed

    Seaman, Scott A; Tannan, Shruti C; Cao, Yiqi; Peirce, Shayn M; Gampper, Thomas J

    2016-01-01

    Cryolipolysis is a noninvasive technique for the reduction of subcutaneous adipose tissue by controlled, localized cooling, causing adipocyte apoptosis, reportedly without affecting surrounding tissue. Although cryolipolysis has a low incidence of adverse side effects 33 cases of paradoxical adipose hyperplasia (PAH) have been reported and the precise pathogenesis of PAH is poorly understood. This present case study of PAH aims to characterize the pathological changes in the adipose tissue of PAH on a cellular level by using multiple different assays [hematoxy lin and eosin staining, LIVE/DEAD staining, BODIPY(®) 558/568 C12 (4,4-Difluoro-5-(2-Thienyl)-4-Bora-3a,4a-Diaza-s-Indacene-3-dodecanoic acid) staining]. to identify the underlying mechanism of PAH and reduce the prevalence of PAH in the future. Tissue with PAH had fewer viable cells, significantly decreased quantities of interstitial cells (p = 0.04), and fewer vessels per adipose tissue area when compared to the control tissue. Adipocytes from the PAH tissue were on average slightly smaller than the control adipocytes. Adipocytes of PAH tissue had irregularly contoured edges when compared to the smooth, round edges of the control tissue. These findings from a neutral third party are contrary to prior reports from the inventors of this technique regarding effects of cryolipolysis on both the microvasculature and interstitial cells in adipose tissue. Our use of different assays to compare cryolipolysis-treated PAH tissue with untreated adipose tissue in the same patient showed adipose tissue that developed PAH was hypocellular and hypovascular. Contrary to prior reports from the inventors, cryolipolysis may cause vessel loss, which could lead to ischemia and/or hypoxia that further contributes to adipocyte death. LEVEL OF EVIDENCE 5: Risk. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  14. Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment.

    PubMed

    Alboni, S; van Dijk, R M; Poggini, S; Milior, G; Perrotta, M; Drenth, T; Brunello, N; Wolfer, D P; Limatola, C; Amrein, I; Cirulli, F; Maggi, L; Branchi, I

    2017-04-01

    Selective serotonin reuptake inhibitors (SSRIs) represent the most common treatment for major depression. However, their efficacy is variable and incomplete. In order to elucidate the cause of such incomplete efficacy, we explored the hypothesis positing that SSRIs may not affect mood per se but, by enhancing neural plasticity, render the individual more susceptible to the influence of the environment. Consequently, SSRI administration in a favorable environment promotes a reduction of symptoms, whereas in a stressful environment leads to a worse prognosis. To test such hypothesis, we exposed C57BL/6 mice to chronic stress in order to induce a depression-like phenotype and, subsequently, to fluoxetine treatment (21 days), while being exposed to either an enriched or a stressful condition. We measured the most commonly investigated molecular, cellular and behavioral endophenotypes of depression and SSRI outcome, including depression-like behavior, neurogenesis, brain-derived neurotrophic factor levels, hypothalamic-pituitary-adrenal axis activity and long-term potentiation. Results showed that, in line with our hypothesis, the endophenotypes investigated were affected by the treatment according to the quality of the living environment. In particular, mice treated with fluoxetine in an enriched condition overall improved their depression-like phenotype compared with controls, whereas those treated in a stressful condition showed a distinct worsening. Our findings suggest that the effects of SSRI on the depression- like phenotype is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.

  15. Cognitive load effects on early visual perceptual processing.

    PubMed

    Liu, Ping; Forte, Jason; Sewell, David; Carter, Olivia

    2018-05-01

    Contrast-based early visual processing has largely been considered to involve autonomous processes that do not need the support of cognitive resources. However, as spatial attention is known to modulate early visual perceptual processing, we explored whether cognitive load could similarly impact contrast-based perception. We used a dual-task paradigm to assess the impact of a concurrent working memory task on the performance of three different early visual tasks. The results from Experiment 1 suggest that cognitive load can modulate early visual processing. No effects of cognitive load were seen in Experiments 2 or 3. Together, the findings provide evidence that under some circumstances cognitive load effects can penetrate the early stages of visual processing and that higher cognitive function and early perceptual processing may not be as independent as was once thought.

  16. Cellular and behavioral effects of stilbene resveratrol analogues: implications for reducing the deleterious effects of aging.

    PubMed

    Joseph, James A; Fisher, Derek R; Cheng, Vivian; Rimando, Agnes M; Shukitt-Hale, Barbara

    2008-11-26

    Research suggests that polyphenolic compounds contained in fruits and vegetables that are rich in color may have potent antioxidant and anti-inflammatory activities. The present studies determined if stilbene (e.g., resveratrol) compounds would be efficacious in reversing the deleterious effects of aging in 19 month old Fischer 344 rats. Experiment I utilized resveratrol and six resveratrol analogues and examined their efficacies in preventing dopamine-induced decrements in calcium clearance following oxotremorine-induced depolarization in COS-7 cells transfected with M1 muscarinic receptors (MAChR) that we have shown previously to be sensitive to oxidative stressors. Experiment II utilized the most efficacious analogue (pterostilbene) from experiment I and fed aged rats a diet with a low (0.004%) or a high (0.016%) concentration of pterostilbene. Results indicated that pterostilbene was effective in reversing cognitive behavioral deficits, as well as dopamine release, and working memory was correlated with pterostilbene levels in the hippocampus.

  17. Effects of cellular sorption on mercury bioavailability and methylmercury production by Desulfovibrio desulfuricans ND132

    DOE PAGES

    Liu, Yu-Rong; Lu, Xia; Zhao, Linduo; ...

    2016-11-14

    Microbial conversion of inorganic mercury (IHg) to methylmercury (MeHg) is a significant environmental concern because of the bioaccumulation and biomagnification of toxic MeHg in the food web. Laboratory incubation studies have shown that, despite the presence of large quantities of IHg in cell cultures, MeHg biosynthesis often reaches a plateau or a maximum within hours or a day by an as yet unexplained mechanism. In this paper, we report that mercuric Hg(II) can be taken up rapidly by cells of Desulfovibrio desulfuricans ND132, but a large fraction of the Hg(II) is unavailable for methylation because of strong cellular sorption. Thiols,more » such as cysteine, glutathione, and penicillamine, added either simultaneously with Hg(II) or after cells have been exposed to Hg(II), effectively desorb or mobilize the bound Hg(II), leading to a substantial increase in MeHg production. The amount of thiol-desorbed Hg(II) is strongly correlated to the amount of MeHg produced (r = 0.98). Furthermore, cells do not preferentially take up Hg(II)–thiol complexes, but Hg(II)–ligand exchange between these complexes and the cell-associated proteins likely constrains Hg(II) uptake and methylation. Finally, we suggest that, aside from aqueous chemical speciation of Hg(II), binding and exchange of Hg(II) between cells and complexing ligands such as thiols and naturally dissolved organics in solution is an important controlling mechanism of Hg(II) bioavailability, which should be considered when predicting MeHg production in the environment.« less

  18. SAR Simulation with Magneto Chiral Effects for Human Head Radiated from Cellular Phones

    NASA Astrophysics Data System (ADS)

    Torres-Silva, H.

    2008-09-01

    A numerical method for a microwave signal emitted by a cellular phone, propagating in a magneto-chiral media, characterized by an extended Born-Fedorov formalism, is presented. It is shown that the use of a cell model, combined with a real model of the human head, derived from the magnetic resonance of images allows a good determination of the near fields induced in the head when the brain chirality and the battery magnetic field are considered together. The results on a 2-Dim human head model show the evolution of the specific absorption rate, (SAR coefficient) and the spatial peak specific absorption rate which are sensitives to the magneto-chiral factor, which is important in the brain layer. For GSM/PCN phones, extremely low frequency real pulsed magnetic fields (in the order of 10 to 60 milligauss) are added to the model through the whole of the user's head. The more important conclusion of our work is that the head absorption is bigger than the results for a classical model without the magneto chiral effect. Hot spots are produced due to the combination of microwave and the magnetic field produced by the phone's operation. The FDTD method was used to compute the SARs inside the MRI based head models consisting of various tissues for 1.8 GHz. As a result, we found that in the head model having more than four kinds of tissue, the localized peak SAR reaches maximum inside the head for over five tissues including skin, bone, blood and brain cells.

  19. Molecular and Cellular Effects Induced in Mytilus galloprovincialis Treated with Oxytetracycline at Different Temperatures

    PubMed Central

    Banni, Mohamed; Sforzini, Susanna; Franzellitti, Silvia; Oliveri, Caterina; Viarengo, Aldo; Fabbri, Elena

    2015-01-01

    The present study evaluatedthe interactive effects of temperature (16°C and 24°C) and a 4-day treatment with the antibiotic oxytetracycline (OTC) at 1 and 100μg/L on cellular and molecular parameters in the mussel Mytilus galloprovincialis. Lysosomal membrane stability (LMS), a sensitive biomarker of impaired health status in this organism, was assessed in the digestive glands. In addition, oxidative stress markers and the expression of mRNAs encoding proteins involved in antioxidant defense (catalase (cat) and glutathione-S-transferase (gst)) and the heat shock response (hsp90, hsp70, and hsp27) were evaluated in the gills, the target tissue of soluble chemicals. Finally, cAMP levels, which represent an important cell signaling pathway related to oxidative stress and the response to temperature challenges, were also determined in the gills. Exposure to heat stress as well as to OTC rendered a decrease in LMS and an increase in malonedialdehyde accumulation (MDA). CAT activity was not significantly modified, whereas GST activity decreased at 24°C. Cat and gst expression levels were reduced in animals kept at 24°C compared to 16°C in the presence or absence of OTC. At 16°C, treatment with OTC caused a significant increase in cat and gst transcript levels. Hsp27 mRNA was significantly up-regulated at all conditions compared to controls at 16°C. cAMP levels were increased at 24°C independent of the presence of OTC. PCA analysis showed that 37.21% and 25.89% of the total variance was explained by temperature and OTC treatment, respectively. Interestingly, a clear interaction was observed in animals exposed to both stressors increasing LMS and MDA accumulation and reducing hsp27 gene expression regulation. These interactions may suggest a risk for the organisms due to temperature increases in contaminated seawaters. PMID:26067465

  20. Early vitrectomy effective for Norrie disease.

    PubMed

    Walsh, Mark K; Drenser, Kimberly A; Capone, Antonio; Trese, Michael T

    2010-04-01

    To review our experience with Norrie disease to determine if early vitrectomy abrogates the natural history of this rare disease; namely, bilateral no light perception visual acuity and phthisis bulbi. We retrospectively reviewed the medical records of all patients seen in our tertiary care pediatric retinal clinical practice from 1988 through 2008 with a potential diagnosis of Norrie disease. Inclusion required not only clinical findings consistent with Norrie disease but also genetics and/or a family history consistent with Norrie disease. Medical record review revealed 14 boys with clinically diagnosed Norrie disease and either Norrie disease gene (NDP) mutations noted on genetic testing (13 patients) and/or a clear family history consistent with Norrie disease (4 patients). All 14 boys with definite Norrie disease had vitrectomy with or without lensectomy in at least 1 eye prior to 12 months of age. Of the 14 boys with definite Norrie disease, 7 maintained at least light perception visual acuity in 1 eye and 3 had no light perception visual acuity bilaterally; visual acuity data were not available for 4 patients. Only 2 of 24 (8%) eyes became phthisical. Historically, no treatment has been offered to mitigate the dismal natural history of Norrie disease. We recommend consideration of early vitrectomy in Norrie disease.

  1. Effect of LED photobiomodulation on fluorescent light induced changes in cellular ATPases and Cytochrome c oxidase activity in Wistar rat.

    PubMed

    A, Ahamed Basha; C, Mathangi D; R, Shyamala

    2016-12-01

    Fluorescent light exposure at night alters cellular enzyme activities resulting in health defects. Studies have demonstrated that light emitting diode photobiomodulation enhances cellular enzyme activities. The objectives of this study are to evaluate the effects of fluorescent light induced changes in cellular enzymes and to assess the protective role of pre exposure to 670 nm LED in rat model. Male Wistar albino rats were divided into 10 groups of 6 animals each based on duration of exposure (1, 15, and 30 days) and exposure regimen (cage control, exposure to fluorescent light [1800 lx], LED preexposure followed by fluorescent light exposure and only LED exposure). Na + -K + ATPase, Ca 2+ ATPase, and cytochrome c oxidase of the brain, heart, kidney, liver, and skeletal muscle were assayed. Animals of the fluorescent light exposure group showed a significant reduction in Na + -K + ATPase and Ca 2+ ATPase activities in 1 and 15 days and their increase in animals of 30-day group in most of the regions studied. Cytochrome c oxidase showed increase in their level at all the time points assessed in most of the tissues. LED light preexposure showed a significant enhancement in the degree of increase in the enzyme activities in almost all the tissues and at all the time points assessed. This study demonstrates the protective effect of 670 nm LED pre exposure on cellular enzymes against fluorescent light induced change.

  2. Multi-parameter phenotypic profiling: using cellular effects to characterize small-molecule compounds.

    PubMed

    Feng, Yan; Mitchison, Timothy J; Bender, Andreas; Young, Daniel W; Tallarico, John A

    2009-07-01

    Multi-parameter phenotypic profiling of small molecules provides important insights into their mechanisms of action, as well as a systems level understanding of biological pathways and their responses to small molecule treatments. It therefore deserves more attention at an early step in the drug discovery pipeline. Here, we summarize the technologies that are currently in use for phenotypic profiling--including mRNA-, protein- and imaging-based multi-parameter profiling--in the drug discovery context. We think that an earlier integration of phenotypic profiling technologies, combined with effective experimental and in silico target identification approaches, can improve success rates of lead selection and optimization in the drug discovery process.

  3. Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells

    PubMed Central

    Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Lee, In Kyung; Nam, Seon Young

    2017-01-01

    Abstract Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation. PMID:28122968

  4. Biological Perspectives on the Effects of Early Psychosocial Experience

    ERIC Educational Resources Information Center

    Marshall, Peter J.; Kenney, Justin W.

    2009-01-01

    There is much current interest in how adverse experiences early in life might affect certain elements of physiological, behavioral, and psychological functioning across the lifespan. Recent conceptual frameworks for studying the effects of early experience have involved constructs such as experience-expectant, experience-dependent, and…

  5. Effects of Critical Thinking Intervention for Early Childhood Teacher Candidates

    ERIC Educational Resources Information Center

    Han, Heejeong Sophia; Brown, E. Todd

    2013-01-01

    This study is based on an intervention designed to enhance early childhood teacher candidates' critical thinking abilities. The concept, elements, standards, and traits of critical thinking were integrated into the main course contents, and the effects of the intervention were examined. The results indicated that early childhood teacher…

  6. The Importance of Effective Behaviour Screening in the Early Years

    ERIC Educational Resources Information Center

    Tyler-Merrick, Gaye; Church, John

    2013-01-01

    Early intervention for children with behavioural difficulties can be effective in terms of outcomes for both the children and their families. Early intervention can save a child from long-term outcomes such as school failure, peer rejection and later offending. However, in terms of accurate assessment of young children's behavioural difficulties,…

  7. Alginate-Iron Speciation and Its Effect on In Vitro Cellular Iron Metabolism

    PubMed Central

    Horniblow, Richard D.; Dowle, Miriam; Iqbal, Tariq H.; Latunde-Dada, Gladys O.; Palmer, Richard E.

    2015-01-01

    Alginates are a class of biopolymers with known iron binding properties which are routinely used in the fabrication of iron-oxide nanoparticles. In addition, alginates have been implicated in influencing human iron absorption. However, the synthesis of iron oxide nanoparticles employs non-physiological pH conditions and whether nanoparticle formation in vivo is responsible for influencing cellular iron metabolism is unclear. Thus the aims of this study were to determine how alginate and iron interact at gastric-comparable pH conditions and how this influences iron metabolism. Employing a range of spectroscopic techniques under physiological conditions alginate-iron complexation was confirmed and, in conjunction with aberration corrected scanning transmission electron microscopy, nanoparticles were observed. The results infer a nucleation-type model of iron binding whereby alginate is templating the condensation of iron-hydroxide complexes to form iron oxide centred nanoparticles. The interaction of alginate and iron at a cellular level was found to decrease cellular iron acquisition by 37% (p < 0.05) and in combination with confocal microscopy the alginate inhibits cellular iron transport through extracellular iron chelation with the resulting complexes not internalised. These results infer alginate as being useful in the chelation of excess iron, especially in the context of inflammatory bowel disease and colorectal cancer where excess unabsorbed luminal iron is thought to be a driver of disease. PMID:26378798

  8. The cellular uptake and transport of zein nanoparticles: Effect of sodium caseinate

    USDA-ARS?s Scientific Manuscript database

    Cellular evaluation of zein nanoparticles has not been studied systematically due to their poor redispersibility. Caseinate (CAS) stabilized zein nanoparticles have been recently developed with better redispersibility in salt solutions. In this study, zein-CAS nanoparticles were prepared with differ...

  9. Effect of socioeconomic status disparity on child language and neural outcome: how early is early?

    PubMed

    Hurt, Hallam; Betancourt, Laura M

    2016-01-01

    It is not news that poverty adversely affects child outcome. The literature is replete with reports of deleterious effects on developmental outcome, cognitive function, and school performance in children and youth. Causative factors include poor nutrition, exposure to toxins, inadequate parenting, lack of cognitive stimulation, unstable social support, genetics, and toxic environments. Less is known regarding how early in life adverse effects may be detected. This review proposes to elucidate "how early is early" through discussion of seminal articles related to the effect of socioeconomic status on language outcome and a discussion of the emerging literature on effects of socioeconomic status disparity on brain structure in very young children. Given the young ages at which such outcomes are detected, the critical need for early targeted interventions for our youngest is underscored. Further, the fiscal reasonableness of initiating quality interventions supports these initiatives. As early life adversity produces lasting and deleterious effects on developmental outcome and brain structure, increased focus on programs and policies directed to reducing the impact of socioeconomic disparities is essential.

  10. Effect of Nitrogen on Cellular Production and Release of the Neurotoxin Anatoxin-A in a Nitrogen-Fixing Cyanobacterium

    PubMed Central

    Gagnon, Alexis; Pick, Frances R.

    2012-01-01

    Anatoxin-a (ANTX) is a neurotoxin produced by several freshwater cyanobacteria and implicated in lethal poisonings of domesticated animals and wildlife. The factors leading to its production in nature and in culture are not well understood. Resource availability may influence its cellular production as suggested by the carbon-nutrient hypothesis, which links the amount of secondary metabolites produced by plants or microbes to the relative abundance of nutrients. We tested the effects of nitrogen supply (as 1, 5, and 100% N of standard cyanobacterial medium corresponding to 15, 75, and 1500 mg L−1 of NaNO3 respectively) on ANTX production and release in a toxic strain of the planktonic cyanobacterium Aphanizomenon issatschenkoi (Nostocales). We hypothesized that nitrogen deficiency might constrain the production of ANTX. However, the total concentration and more significantly the cellular content of anatoxin-a peaked (max. 146 μg/L and 1683 μg g−1 dry weight) at intermediate levels of nitrogen supply when N-deficiency was evident based on phycocyanin to chlorophyll a and carbon to nitrogen ratios. The results suggest that the cellular production of anatoxin-a may be stimulated by moderate nitrogen stress. Maximal cellular contents of other cyanotoxins have recently been reported under severe stress conditions in another Nostocales species. PMID:22701451

  11. [Effect of cellular immune supportive treatment on immunity of esophageal carcinoma patients after modern two-field lymph node dissection].

    PubMed

    Wang, Jun-Ye; Ma, Guo-Wei; Dai, Shu-Qin; Rong, Tie-Hua; Wang, Xin; Lin, Peng; Ye, Wen-Feng; Zhang, Lan-Jun; Li, Xiao-Dong; Zhang, Xu; Yao, Guang-Yu

    2007-07-01

    Cellular immunity suppression is marked in patients with esophageal carcinoma, which may be resulted temporarily from surgical injury. This study was to evaluate the effect of cellular immune supportive treatment on cellular immunity of patients with esophageal carcinoma. A total of 60 patients with thoracic esophageal carcinoma, received two-field dissection, were randomized into control group and trial (immune supportive treatment) group. The patients in trial group were injected with Shenqi injection after operation; the patients in control group received no immune supportive treatment. Peripheral blood samples were obtained before operation, and 3 and 9 days after operation. AgNOR (argyrophilic nucleolar organizer regions) activity in peripheral blood T lymphocytes was measured by tumor immune microphotometry. T cell subsets were measured by flow cytometry. The proportions of CD3+CD4+ and CD4+/CD8+ cells were significantly higher in trial group than in control group at 3 days after operation (P < 0.05). The amount of AgNOR and proportions of CD3+, CD3+CD4+, CD4+/CD8+, and CD4+CD25+ cells were significantly higher in trial group than in control group at 9 days after operation (P < 0.05). There was no significant difference in 1-year survival rate between the 2 groups (P > 0.05). Shenqi injection could obviously improve cellular immunity of the esophageal carcinoma patients after modern two-field dissection.

  12. Protective effect of gallic acid and Syzygium cumini extract against oxidative stress-induced cellular injury in human lymphocytes.

    PubMed

    De Bona, Karine Santos; Bonfanti, Gabriela; Bitencourt, Paula Eliete Rodrigues; da Silva, Thainan Paz; Borges, Raphaela Maleski; Boligon, Aline; Pigatto, Aline; Athayde, Margareth Lynde; Moretto, Maria Beatriz

    2016-01-01

    Syzygium cumini (Myrtaceae) presents antioxidant, anti-inflammatory, hypoglycemic and antibacterial effects; however, the cellular and molecular mechanisms of action in the immune system are not yet completely elucidated. This study evaluates the in vitro effect of gallic acid and aqueous S. cumini leaf extract (ASc) on adenosine deaminase (ADA) and dipeptidyl peptidase IV (DPP-IV) activities, cell viability and oxidative stress parameters in lymphocytes exposed to 2, 2'-azobis-2-amidinopropane dihydrochloride (AAPH). Lymphocytes were incubated with ASc (100 and 500 µg/ml) and gallic acid (50 and 200 µM) at 37 °C for 30 min followed by incubation with AAPH (1 mM) at 37 °C for 2 h. After the incubation time, the lymphocytes were used for determinations of ADA, DPP-IV and lactate dehydrogenase (LDH) activities, lipid peroxidation, protein thiol (P-SH) group levels and cellular viability by colorimetric methods. (i) HPLC fingerprinting of ASc revealed the presence of catechin, epicatechin, rutin, quercitrin, isoquercitrin, quercetin, kaempferol and chlorogenic, caffeic, gallic and ellagic acids; (ii) for the first time, ASc reduced the AAPH-induced increase in ADA activity, but no effect was observed on DPP-IV activity; (iii) ASc increased P-SH groups and cellular viability and decreased LDH activity, but was not able to reduce the AAPH-induced lipid peroxidation; (iv) gallic acid showed less protective effects than ASc. ASc affects the purinergic system and may modulate adenosine levels, indicating that the extract of this plant exhibits immunomodulatory properties. ASc also may potentially prevent the cellular injury induced by oxidative stress, highlighting its cytoprotective effects.

  13. Effects of age and the use of hands-free cellular phones on driving behavior and task performance.

    PubMed

    Liu, Yung-Ching; Ou, Yang-Kun

    2011-12-01

    This study used a driving simulator to investigate the effect of using a Bluetooth hands-free cellular phone earpiece on the driving behavior of two age groups. Forty-eight participants (24 aged 20-26 and 24 aged 65-73) were examined to assess their performance on the following divided-attention tasks under 2 driving load conditions (high and low): (1) attempting to maintain the speed limit and (2) using a cellular phone while driving. The length of the call conversation (long vs. short) and the conversational content (complex vs. simple) were manipulated as within-subject independent variables. The driving behavior of the participants, their task reaction times and accuracy, and subjective ratings were collected as dependent variables. The results indicate that under low driving loads, short talk times, and simple conversational content, the driving behavior of the participants showed low variance in the vehicle's mean speed. In contrast, complex conversation had a significantly negative impact on driving behavior. Notably, under a low driving load, motorists' driving behaviors, measured in lateral acceleration, caused significantly smaller variance in complex conversations compared to no call and simple conversations. The use of a hands-free cellular phone affected the performance (acceleration, lane deviation, reaction time, and accuracy) of older drivers significantly more than younger drivers. While performing divided attention tasks, the accuracy of the older drivers was 66.3 percent and that of the younger drivers was 96.3 percent. Although this study did not find a clear impact of cellular phone use on the driving behavior of younger drivers, their divided-attention task reaction times and accuracy were better under no-call than calling conditions. This study indicates that the use of hands-free cellular phones could significantly affect the safety of driving among the older and present risks, although lesser, for younger drivers.

  14. Effect of trehalose as an additive to dimethyl sulfoxide solutions on ice formation, cellular viability, and metabolism.

    PubMed

    Solocinski, Jason; Osgood, Quinn; Wang, Mian; Connolly, Aaron; Menze, Michael A; Chakraborty, Nilay

    2017-04-01

    Cryopreservation is the only established method for long-term preservation of cells and cellular material. This technique involves preservation of cells and cellular components in the presence of cryoprotective agents (CPAs) at liquid nitrogen temperatures (-196 °C). The organic solvent dimethyl sulfoxide (Me 2 SO) is one of the most commonly utilized CPAs and has been used with various levels of success depending on the type of cells. In recent years, to improve cryogenic outcomes, the non-reducing disaccharide trehalose has been used as an additive to Me 2 SO-based freezing solutions. Trehalose is a naturally occurring non-toxic compound found in bacteria, fungi, plants, and invertebrates which has been shown to provide cellular protection during water-limited states. The mechanism by which trehalose improves cryopreservation outcomes remains not fully understood. Raman microspectroscopy is a powerful tool to provide valuable insight into the nature of interactions among water, trehalose, and Me 2 SO during cryopreservation. We found that the addition of trehalose to Me 2 SO based CPA solutions dramatically reduces the area per ice crystals while increasing the number of ice crystals formed when cooled to -40 or -80 °C. Differences in ice-formation patterns were found to have a direct impact on cellular viability. Despite the osmotic stress caused by addition of 100 mM trehalose, improvement in cellular viability was observed. However, the substantial increase in osmotic pressure caused by trehalose concentrations above 100 mM may offset the beneficial effects of changing the morphology of the ice crystals achieved by addition of this sugar. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Cellular interface morphologies in directional solidification. III - The effects of heat transfer and solid diffusivity

    NASA Technical Reports Server (NTRS)

    Ungar, Lyle H.; Bennett, Mark J.; Brown, Robert A.

    1985-01-01

    The shape and stability of two-dimensional finite-amplitude cellular interfaces arising during directional solidification are compared for several solidification models that account differently for latent heat released at the interface, unequal thermal conductivities of melt and solid, and solute diffusivity in the solid. Finite-element analysis and computer-implemented perturbation methods are used to analyze the families of steadily growing cellular forms that evolve from the planar state. In all models a secondary bifurcation between different families of finite-amplitude cells exists that halves the spatial wavelength of the stable interface. The quantitative location of this transition is very dependent on the details of the model. Large amounts of solute diffusion in the solid retard the growth of large-amplitude cells.

  16. Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2017-11-01

    In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, both minimally-porous solid and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and analyzed. Microstructures of the solid forms and the cell walls range from single-phase solid solutions of the excipient and a small amount of drug molecules to two-phase composites of the excipient and tightly packed drug particles. Results of dissolution experiments show that the minimally-porous solid forms disintegrate and release drug by slow surface erosion. The erosion rate decreases as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration time is independent of drug weight fraction. Drug release models suggest that the solid forms erode by convective mass transfer of the faster-eroding excipient if the drug volume fraction is small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite. Conversely, the disintegration rate of the cellular forms is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, and the particles are enveloped by the excipient during melt-processing, the drug particles cannot hinder diffusion through the excipient across the walls. Thus the disintegration time of the cellular forms is mostly unaffected by the volume fraction of drug

  17. The Effect of Price: Early Observations.

    ERIC Educational Resources Information Center

    Hunter, Karen

    Scientific journal publishers have very little commercial experience with electronic full text distribution and it is difficult to segregate the effect of pricing on user acceptance and behavior. This paper examines some of the known experiences and ongoing and proposed experiments to get a sense of the interaction of pricing and user acceptance…

  18. Effect of 2,4-Dichlorophenoxyacetic acid herbicide Escherichia coli growth, chemical, composition, and cellular envelope

    USGS Publications Warehouse

    Carr, R.S.; Biedenbach, J.M.; Hooten, R.L.

    2001-01-01

    2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide widely used in the world and mainly excreted by the renal route in exposed humans and animals. Herbicides can affect other nontarget organisms, such as Escherichia coli. We observed that a single exposure to 1 mM 2,4-D diminished growth and total protein content in all E. coli strains tested in vitro. In addition, successive exposures to 0.01 mM 2,4-D had a toxic effect decreasing growth up to early stationary phase. Uropathogenic E. coli adhere to epithelial cells mediated by fimbriae, adhesins, and hydrophobic properties. 2,4-D exposure of uropathogenic E. coli demonstrated altered hydrophobicity and fimbriation. Hydrophobicity index values obtained by partition in p-xylene/water were 300-420% higher in exposed cells than in control ones. Furthermore, values of hemagglutination titer, protein contents in fimbrial crude extract, and electron microscopy demonstrated a significant diminution of fimbriation in treated cells. Other envelope alterations could be detected, such as lipoperoxidation, evidenced by decreased polyunsaturated fatty acids and increased lipid degradation products (malonaldehyde), and motility diminution. These alterations decreased cell adherence to erythrocytes, indicating a diminished pathogenic capacity of the 2,4-D-exposed E. coli. ?? 2001 by John Wiley & Sons, Inc.

  19. Early-life nutritional effects on the female reproductive system.

    PubMed

    Chan, K A; Tsoulis, M W; Sloboda, D M

    2015-02-01

    There is now considerable epidemiological and experimental evidence indicating that early-life environmental conditions, including nutrition, affect subsequent development in later life. These conditions induce highly integrated responses in endocrine-related homeostasis, resulting in persistent changes in the developmental trajectory producing an altered adult phenotype. Early-life events trigger processes that prepare the individual for particular circumstances that are anticipated in the postnatal environment. However, where the intrauterine and postnatal environments differ markedly, such modifications to the developmental trajectory may prove maladaptive in later life. Reproductive maturation and function are similarly influenced by early-life events. This should not be surprising, because the primordial follicle pool is established early in life and is thus vulnerable to early-life events. Results of clinical and experimental studies have indicated that early-life adversity is associated with a decline in ovarian follicular reserve, changes in ovulation rates, and altered age at onset of puberty. However, the underlying mechanisms regulating the relationship between the early-life developmental environment and postnatal reproductive development and function are unclear. This review examines the evidence linking early-life nutrition and effects on the female reproductive system, bringing together clinical observations in humans and experimental data from targeted animal models. © 2015 Society for Endocrinology.

  20. The effect of feedback on attitudes toward cellular phone use while driving: a comparison between novice and experienced drivers.

    PubMed

    Wang, Ying; Zhang, Wei; Reimer, Bryan; Lavallière, Martin; Lesch, Mary F; Horrey, William J; Wu, Su

    2010-10-01

    To assess and compare the effectiveness of a simulation-based approach to change drivers' attitudes toward cellular phone use while driving for younger novice and older experienced drivers. Thirty young novice drivers were tested on a driving simulator in this study. Their performance in dealing with driving tasks was measured for a single task and dual tasks (driving while using a cellular phone) and compared to 30 older experienced drivers tested previously in another study. Half of the younger drivers received video-based feedback regarding their performance in the two conditions, with an emphasis on the contribution of dual-tasking to degraded performance. The other half did not receive any performance feedback. Drivers' perceptions and attitudes toward cellular phone use while driving were investigated by a questionnaire before, immediately after, and again one month following the simulation-based testing for both groups of drivers (feedback; no feedback). All drivers (including the novice and experienced) reported willingness to engage in driving and talking on a cellular phone in some situations. The simulated driving test showed that a secondary cellular phone task significantly degraded driving performance for both the novice and the experienced drivers. The feedback treatment group (both the novice and the experienced) showed significant attitude change toward cellular phone use while driving (toward being less favorable), whereas the control group had no attitude change. At the one-month follow-up, the benefit of feedback was sustained more so in the experienced driver group than the novice driver group, although both groups still benefited relative to the control conditions. Simulation-based feedback training is promising for short-term education in novice drivers but may be more effective in the long-term for drivers with higher levels of experience. Drivers with more experience appear to have a greater, more sustained benefit from the training than

  1. First cellular approach of the effects of global warming on groundwater organisms: a study of the HSP70 gene expression.

    PubMed

    Colson-Proch, Céline; Morales, Anne; Hervant, Frédéric; Konecny, Lara; Moulin, Colette; Douady, Christophe J

    2010-05-01

    Whereas the consequences of global warming at population or community levels are well documented, studies at the cellular level are still scarce. The study of the physiological or metabolic effects of such small increases in temperature (between +2 degrees C and +6 degrees C) is difficult because they are below the amplitude of the daily or seasonal thermal variations occurring in most environments. In contrast, subterranean biotopes are highly thermally buffered (+/-1 degrees C within a year), and underground water organisms could thus be particularly well suited to characterise cellular responses of global warming. To this purpose, we studied genes encoding chaperone proteins of the HSP70 family in amphipod crustaceans belonging to the ubiquitous subterranean genus Niphargus. An HSP70 sequence was identified in eight populations of two complexes of species of the Niphargus genus (Niphargus rhenorhodanensis and Niphargus virei complexes). Expression profiles were determined for one of these by reverse transcription and quantitative polymerase chain reaction, confirming the inducible nature of this gene. An increase in temperature of 2 degrees C seemed to be without effect on N. rhenorhodanensis physiology, whereas a heat shock of +6 degrees C represented an important thermal stress for these individuals. Thus, this study shows that although Niphargus individuals do not undergo any daily or seasonal thermal variations in underground water, they display an inducible HSP70 heat shock response. This controlled laboratory-based physiological experiment constitutes a first step towards field investigations of the cellular consequences of global warming on subterranean organisms.

  2. Bioaccessibility, Cellular Uptake, and Transport of Astaxanthin Isomers and their Antioxidative Effects in Human Intestinal Epithelial Caco-2 Cells.

    PubMed

    Yang, Cheng; Zhang, Hua; Liu, Ronghua; Zhu, Honghui; Zhang, Lianfu; Tsao, Rong

    2017-11-29

    The bioaccessibility, bioavailability, and antioxidative activities of three astaxanthin geometric isomers were investigated using an in vitro digestion model and human intestinal Caco-2 cells. This study demonstrated that the trans-cis isomerization of all-E-astaxanthin and the cis-trans isomerization of Z-astaxanthins could happen both during in vitro gastrointestinal digestion and cellular uptake processes. 13Z-Astaxanthin showed higher bioaccessibility than 9Z- and all-E-astaxanthins during in vitro digestion, and 9Z-astaxanthin exhibited higher transport efficiency than all-E- and 13Z-astaxanthins. These might explain why 13Z- and 9Z-astaxanthins are found at higher concentrations in human plasma than all-E-astaxanthin in reported studies. All three astaxanthin isomers were effective in maintaining cellular redox homeostasis as seen in the antioxidant enzyme (CAT, SOD) activities ; 9Z- and 13Z- astaxanthins exhibited a higher protective effect than all-E-astaxanthin against oxidative stress as demonstrated by the lower cellular uptake of Z-astaxanthins and lower secretion and gene expression of the pro-inflammatory cytokine IL-8 in Caco-2 cells treated with H 2 O 2 . We conclude, for the first time, that Z-astaxanthin isomers may play a more important role in preventing oxidative stress induced intestinal diseases.

  3. Long term effects of early adversity on cognitive function.

    PubMed

    Richards, M; Wadsworth, M E J

    2004-10-01

    To investigate long term effects of early adverse circumstances on cognitive function. Associations between early material home circumstances, parental divorce, maternal management and understanding, and cognitive function in childhood, adolescence, and adulthood were analysed using multiple linear regression, controlling for sex, parental SES, and birth order in 1339 males and females from the MRC National Survey of Health and Development. Early adverse circumstances were strongly associated with lower cognitive ability in childhood and adolescence, and were detectable on measures of verbal ability, memory, and speed and concentration in midlife. However, these long term effects were mostly explained by the effects of adversity on childhood or adolescent cognitive ability or by differences in educational attainment and adult social class. An exception was the effect of poor material home conditions on visual search speed at 53 years, which was maintained after controlling for adolescent ability, as well as further control for educational attainment, adult social class, physical growth, cigarette smoking, and affective state. There was no evidence of more rapid decline in memory and psychomotor function across middle age in those exposed to early adversity. The effect of early adversity on cognitive function tracks across the life course at least as far as middle age, although there was little evidence from this study of effect amplification over this interval. Nevertheless, in view of the persistence of child poverty in the industrialised world, these findings give cause for concern.

  4. Activation of autophagy by stress-activated signals as a cellular self-defense mechanism against the cytotoxic effects of MBIC in human breast cancer cells in vitro.

    PubMed

    Hasanpourghadi, Mohadeseh; Majid, Nazia Abdul; Mustafa, Mohd Rais

    2018-06-01

    We recently reported that methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) is a microtubule targeting agent (MTA) with multiple mechanisms of action including apoptosis in two human breast cancer cell-lines MCF-7 and MDA-MB-231. In the present study, investigation of early molecular events following MBIC treatment demonstrated the induction of autophagy. This early (<24 h) response to MBIC was characterized by accumulation of autophagy markers; LC3-II, Beclin1, autophagic proteins (ATGs) and collection of autophagosomes but with different variations in the two cell-lines. MBIC-induced autophagy was associated with generation of reactive oxygen species (ROS). In parallel, an increased activation of SAPK/JNK pathway was detected, as an intersection of ROS production and induction of autophagy. The cytotoxic effect of MBIC was enhanced by inhibition of autophagy through blockage of SAPK/JNK signaling, suggesting that MBIC-induced autophagy, is a possible cellular self-defense mechanism against toxicity of this agent in both breast cancer cell-lines. The present findings suggest that inhibition of autophagy eliminates the cytoprotective activity of MDA-MB-231 and MCF-7 cells, and sensitizes both the aggressive and non-aggressive human breast cancer cell-lines to the cytotoxic effects of MBIC. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Cellular effects of the microtubule-targeting agent peloruside A in hypoxia-conditioned colorectal carcinoma cells.

    PubMed

    Řehulka, Jiří; Annadurai, Narendran; Frydrych, Ivo; Znojek, Pawel; Džubák, Petr; Northcote, Peter; Miller, John H; Hajdúch, Marián; Das, Viswanath

    2017-07-01

    Hypoxia is a prominent feature of solid tumors, dramatically remodeling microtubule structures and cellular pathways and contributing to paclitaxel resistance. Peloruside A (PLA), a microtubule-targeting agent, has shown promising anti-tumor effects in preclinical studies. Although it has a similar mode of action to paclitaxel, it binds to a distinct site on β-tubulin that differs from the classical taxane site. In this study, we examined the unexplored effects of PLA in hypoxia-conditioned colorectal HCT116 cancer cells. Cytotoxicity of PLA was determined by cell proliferation assay. The effects of a pre-exposure to hypoxia on PLA-induced cell cycle alterations and apoptosis were examined by flow cytometry, time-lapse imaging, and western blot analysis of selected markers. The hypoxia effect on stabilization of microtubules by PLA was monitored by an intracellular tubulin polymerization assay. Our findings show that the cytotoxicity of PLA is not altered in hypoxia-conditioned cells compared to paclitaxel and vincristine. Furthermore, hypoxia does not alter PLA-induced microtubule stabilization nor the multinucleation of cells. PLA causes cyclin B1 and G2/M accumulation followed by apoptosis. The cellular and molecular effects of PLA have been determined in normoxic conditions, but there are no reports of PLA effects in hypoxic cells. Our findings reveal that hypoxia preconditioning does not alter the sensitivity of HCT116 to PLA. These data report on the cellular and molecular effects of PLA in hypoxia-conditioned cells for the first time, and will encourage further exploration of PLA as a promising anti-tumor agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Are There Long-Term Effects of Early Child Care?

    ERIC Educational Resources Information Center

    Belsky, Jay; Vandell, Deborah Lowe; Burchinal, Margaret; Clarke-Stewart, K. Alison; McCartney, Kathleen; Owen, Margaret Tresch

    2007-01-01

    Effects of early child care on children's functioning from 4 1/2 years through the end of 6th grade (M age=12.0 years) were examined in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (n=1,364). The results indicated that although parenting was a stronger and more consistent predictor of…

  7. Protective Effect of Garlic on Cellular Senescence in UVB-Exposed HaCaT Human Keratinocytes.

    PubMed

    Kim, Hye Kyung

    2016-07-29

    Ultraviolet (UV) irradiation generates reactive oxygen species (ROS) in the cells, which induces the cellular senescence and photoaging. The present study investigated the protective effects of garlic on photo-damage and cellular senescence in UVB-exposed human keratinocytes, HaCaT cells. An in vitro cell free system was used to examine the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and nitric oxide (NO). The effect of garlic extract on ROS formation, MMP-1 protein and mRNA expressions, cytokines such as interleukin (IL)-1β and IL-6, senescence associated-β-galactosidase (SA-β-gal) activity, and silent information regulator T1 (SIRT1) activity were determined in UVB-irradiated HaCaT cells. Garlic exhibited strong DPPH radical and NO scavenging activity in cell free system exhibiting IC50 values of 2.50 mg/mL and 4.38 mg/mL, respectively. Garlic pretreatment attenuated the production of UVB-induced intracellular ROS. MMP-1 level, which has been known to be induced by ROS, was dramatically elevated by UVB irradiation, and UVB-induced MMP-1 mRNA and protein expressions were significantly reduced by garlic treatment (50 µg/mL) comparable to those of UV-unexposed control cells. UV-induced pro-inflammatory cytokine productions (IL-6 and IL-1β) were significantly inhibited by pretreatment with garlic in a dose-dependent manner. SA-β-gal activity, a classical biomarker of cellular senescence, and SIRT1 activity, which has attracted attention as an anti-aging factor in recent years, were ameliorated by garlic treatment in UV-irradiated HaCaT cells. The present study provides the first evidence of garlic inhibiting UVB-induced photoaging as a result of augmentation of cellular senescence in HaCaT human keratinocytes.

  8. Protective Effect of Garlic on Cellular Senescence in UVB-Exposed HaCaT Human Keratinocytes

    PubMed Central

    Kim, Hye Kyung

    2016-01-01

    Ultraviolet (UV) irradiation generates reactive oxygen species (ROS) in the cells, which induces the cellular senescence and photoaging. The present study investigated the protective effects of garlic on photo-damage and cellular senescence in UVB-exposed human keratinocytes, HaCaT cells. An in vitro cell free system was used to examine the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and nitric oxide (NO). The effect of garlic extract on ROS formation, MMP-1 protein and mRNA expressions, cytokines such as interleukin (IL)-1β and IL-6, senescence associated-β-galactosidase (SA-β-gal) activity, and silent information regulator T1 (SIRT1) activity were determined in UVB-irradiated HaCaT cells. Garlic exhibited strong DPPH radical and NO scavenging activity in cell free system exhibiting IC50 values of 2.50 mg/mL and 4.38 mg/mL, respectively. Garlic pretreatment attenuated the production of UVB-induced intracellular ROS. MMP-1 level, which has been known to be induced by ROS, was dramatically elevated by UVB irradiation, and UVB-induced MMP-1 mRNA and protein expressions were significantly reduced by garlic treatment (50 µg/mL) comparable to those of UV-unexposed control cells. UV-induced pro-inflammatory cytokine productions (IL-6 and IL-1β) were significantly inhibited by pretreatment with garlic in a dose-dependent manner. SA-β-gal activity, a classical biomarker of cellular senescence, and SIRT1 activity, which has attracted attention as an anti-aging factor in recent years, were ameliorated by garlic treatment in UV-irradiated HaCaT cells. The present study provides the first evidence of garlic inhibiting UVB-induced photoaging as a result of augmentation of cellular senescence in HaCaT human keratinocytes. PMID:27483310

  9. A Cost-effectiveness Analysis of Early vs Late Tracheostomy.

    PubMed

    Liu, C Carrie; Rudmik, Luke

    2016-10-01

    The timing of tracheostomy in critically ill patients requiring mechanical ventilation is controversial. An important consideration that is currently missing in the literature is an evaluation of the economic impact of an early tracheostomy strategy vs a late tracheostomy strategy. To evaluate the cost-effectiveness of the early tracheostomy strategy vs the late tracheostomy strategy. This economic analysis was performed using a decision tree model with a 90-day time horizon. The economic perspective was that of the US health care third-party payer. The primary outcome was the incremental cost per tracheostomy avoided. Probabilities were obtained from meta-analyses of randomized clinical trials. Costs were obtained from the published literature and the Healthcare Cost and Utilization Project database. A multivariate probabilistic sensitivity analysis was performed to account for uncertainty surrounding mean values used in the reference case. The reference case demonstrated that the cost of the late tracheostomy strategy was $45 943.81 for 0.36 of effectiveness. The cost of the early tracheostomy strategy was $31 979.12 for 0.19 of effectiveness. The incremental cost-effectiveness ratio for the late tracheostomy strategy compared with the early tracheostomy strategy was $82 145.24 per tracheostomy avoided. With a willingness-to-pay threshold of $50 000, the early tracheostomy strategy is cost-effective with 56% certainty. The adaptation of an early vs a late tracheostomy strategy depends on the priorities of the decision-maker. Up to a willingness-to-pay threshold of $80 000 per tracheostomy avoided, the early tracheostomy strategy has a higher probability of being the more cost-effective intervention.

  10. Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters

    SciTech Connect

    Damodaran, T.V., E-mail: tdamodar@nccu.edu; Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC; Dept of Biology, North Carolina Central University, Durham, NC 27707

    quantitative analysis revealed that the order of severity of damage declines from the spino-cerebellar, ventral, and dorsal tract respectively, suggesting neuroanatomical specificity. Thus, early activation of cell death and cell survival processes may play significant role in the clinical progression and syndromic clinical feature presentation of OPIDN. -- Highlights: Black-Right-Pointing-Pointer Multiple mechanisms of neurodegeneration were indicated in a study on OPIDN model. Black-Right-Pointing-Pointer Altered expressions of BCL2 and GADD45 were recorded in various tissues of CNS. Black-Right-Pointing-Pointer Multiple anomalous cellular (neuronal and astroglial) features were recorded. Black-Right-Pointing-Pointer Anatomical specificity of the neurodegeneration was described.« less

  11. Effect of Cellular Mobile Phone Use and Cetrizine on Hand-Eye Coordination and Visual Acuity.

    PubMed

    Gawit, Kalpita Ganpat; Tiwari, Smita Anand; Kasabe, Gauri Hari; Deshpande, Pradeep Kisanrao; Ghongane, Balasaheb Baburao

    2017-09-01

    Cellular mobile phones are a major cause of distraction especially while driving. The aggressive and inappropriate use of cellular mobile phones has increased the risk of accidents. Similar alerts are available in literature for certain substances and drugs (e.g. second generation anti H1 drug -Cetirizine) which also derange psychomotor performance and parameters of alertness. This study measured variations in hand-eye coordination and visual acuity due to use of cellular mobile phone in comparison to that of commonly used antihistaminic drug viz., single dose Cetirizine 10 mg. It was a single blind, single dose, interventional study, 100 healthy human volunteers divided into two groups. Baseline readings of all volunteers were noted. Group-I (n=50) was Cetirizine group (10mg orally stat), Group -II (n=50) Cellular mobile phone user group. Alertness was tested on hand- steadiness tester (Reaction Time Index = RTI) and on Flicker-fusion apparatus (visual acuity - Critical Flicker Fusion Frequency per second= CFFF/sec). Baseline readings of all volunteers were noted before intervention. Baseline was compared with readings at three hour post-intervention and was analysed by paired t-test. Inter-group comparison of parameters was also done and was analysed by unpaired t-test. The baseline RTI (95.46±41.74, 85.11±39.05) and CFF low and high (40.07±9.970, 40.76±9.309 and 40.42±9.035, 40.48±9.863) respectively, in Cetirizine group and Mobile user group were comparable. The RTI increased significantly (116.4±51.46, 102.8±49.26) in both the groups after intervention. However, there is no significant change in CFF intensity from baseline in either group post-intervention. Concurrent use of mobile phone while performing tasks, showed significant impairment of hand-steadiness which was comparable to that produced by single dose Cetirizine 10 mg and this may be one of the factors contributing to their close association with road traffic accidents.

  12. The Effect of Early Marriages and Early Childbearing on Women's Nutritional Status in India.

    PubMed

    Goli, Srinivas; Rammohan, Anu; Singh, Deepti

    2015-08-01

    The consequences of early childbearing on the growth and nutritional status of women in India has not been quantified in previous studies. Our study aimed to fill this gap by analysing the association between early marriage and early childbearing on nutritional status of Indian women, with a focus on Bihar and Andhra Pradesh, the two states accounting for the highest proportion of women marrying and giving first birth before 18 years of age. Our findings revealed that a substantial number of women were married before 18 years and thereby exposed to early pregnancy. Furthermore, a significantly higher proportion of women in the 'thin' category were married before 18 years, both in the Indian sample (33 %, p < 0.001) and in the selected states, Andhra Pradesh (31 %, p < 0.001) and Bihar (43 %, p < 0.001), compared to those women married at higher ages. Similarly, across all our samples women whose first birth was before age 18 years also had a significantly higher probability of being in the 'thin' category across all our samples. This pattern was also observed for associations between early childbirth and anemia levels. We conclude that the net effect of the early age at marriage and age at first birth on nutritional status is significant. Our results underline the need for preventing early marriages and the consequent high adolescent pregnancies in India, particularly in high prevalence states. This will help to improve nutritional status and health care utilisation among women, thereby, prevent maternal and child mortality and thus, achieve the MDGs 4-5.

  13. Traumatic Brain Injury in Early Childhood: Developmental Effects and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara; Lowenthal, Barbara

    1998-01-01

    Describes the unique effects of traumatic brain injury (TBI) on development in early childhood and offers suggestions for interventions in the cognitive, language, social-emotional, motor, and adaptive domains. Urges more intensive, long-term studies on the immediate and long-term effects of TBI. (Author/DB)

  14. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  15. The Self-Reference Effect on Memory in Early Childhood

    ERIC Educational Resources Information Center

    Cunningham, Sheila J.; Brebner, Joanne L.; Quinn, Francis; Turk, David J.

    2014-01-01

    The self-reference effect in memory is the advantage for information encoded about self, relative to other people. The early development of this effect was explored here using a concrete encoding paradigm. Trials comprised presentation of a self- or other-image paired with a concrete object. In Study 1, 4- to 6-year-old children (N = 53) were…

  16. Effects of fade distribution on a mobile satellite downlink and uplink performance in a frequency reuse cellular configuration

    NASA Technical Reports Server (NTRS)

    Boutin, Karl; Lecours, Michel; Pelletier, Marcel; Delisle, Gilles Y.

    1990-01-01

    In a mobile satellite system with a frequency reuse cellular configuration, significant co-channel interference can be experienced due to the antenna sidelobe level. The signal will be subjected not only to its own fading, but also to the effect of the varying degree of fading on co-channel interferer, and this interference will behave differently in the up and in the down link. This paper presents a quantitative evaluation of the combined effects of fades and co-channel interference on a mobile satellite link.

  17. The effect of sedimentation and diffusion on cellular uptake of gold nanoparticles

    PubMed Central

    Cho, Eun Chul; Zhang, Qiang; Xia, Younan

    2011-01-01

    In vitro experiments typically measure the uptake of nanoparticles by exposing cells at the bottom of a culture plate to a suspension of nanoparticles, which is assumed to be well-dispersed. However, nanoparticles can sediment and this means the concentration of particles on the cell surface and those actually taken up by the cells may be higher than the initial bulk concentration. Here we use upright and inverted cell culture configurations to show that cellular uptake of gold nanoparticles depends on the sedimentation and diffusion velocities of the nanoparticles and is independent of size, shape, density, surface coating and initial concentration of the nanoparticles. Generally more nanoparticles are taken up in the upright configuration than the inverted one and nanoparticles that sediment faster showed greater differences in uptake between the two configurations. Our results suggest that cellular uptake of nanoparticles is sensitive to the way cells are positioned and sedimentation need to be considered when performing in vitro studies for large and heavy nanoparticles. PMID:21516092

  18. Cellular uptake and transport of zein nanoparticles: effects of sodium caseinate.

    PubMed

    Luo, Yangchao; Teng, Zi; Wang, Thomas T Y; Wang, Qin

    2013-08-07

    Cellular evaluation of zein nanoparticles has not been studied systematically due to their poor redispersibility. Caseinate (CAS)-stabilized zein nanoparticles have been recently developed with better redispersibility in salt solutions. In this study, zein-CAS nanoparticles were prepared with different zein/CAS mass ratios. The prepared nanoparticles demonstrated good stabilities to maintain particle size (120-140 nm) in cell culture medium and HBSS buffer at 37 °C. The nanoparticles showed no cytotoxicity for Caco-2 cells for 72 h. CAS not only significantly enhanced cell uptake of zein nanoparticles in a concentration- and time-dependent manner but also remarkably improved epithelial transport through Caco-2 cell monolayer. The cell uptake of zein-CAS nanoparticles indicated an energy-dependent endocytosis process as evidenced by cell uptake under blocking conditions, that is, 4 °C, sodium azide, and colchicine. Fluorescent microscopy clearly showed the internalization of zein-CAS nanoparticles. This study may shed some light on the cellular evaluations of hydrophobic protein nanoparticles.

  19. Toxic effects of magnesium oxide nanoparticles on early developmental and larval stages of zebrafish (Danio rerio).

    PubMed

    Ghobadian, Mehdi; Nabiuni, Mohammad; Parivar, Kazem; Fathi, Mojtaba; Pazooki, Jamileh

    2015-12-01

    Magnesium oxide nanoparticles (MgONPs) are used in medicine, manufacturing and food industries. Because of their extensive application in our daily lives, environmental exposure to these nanoparticles is inevitable. The present study examined the effects of MgONPs on zebrafish (Danio rerio) early developmental stages. The results showed that, at different concentrations, MgONPs induced cellular apoptosis and intracellular reactive oxygen species. The hatching rate and survival of embryos decreased in a dose dependent manner. The 96-h LC50 value of MgONPs on zebrafish survival was 428 mg/l and the 48-h EC50 value of MgONPs on zebrafish embryo hatching rate was 175 mg/l. Moreover different types of malformation were observed in exposed embryos. The results demonstrate the toxic effects of MgONPs on zebrafish embryos and emphasize the need for further studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. The prooxidant action of dietary antioxidants leading to cellular DNA breakage and anticancer effects: implications for chemotherapeutic action against cancer.

    PubMed

    Ullah, M F; Ahmad, Aamir; Khan, Husain Y; Zubair, H; Sarkar, Fazlul H; Hadi, S M

    2013-11-01

    Plant-derived dietary antioxidants have attracted considerable interest in recent past for their ability to induce apoptosis and regression of tumors in animal models. While it is believed that the antioxidant properties of these agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, it could not account for apoptosis induction and chemotherapeutic observations. In this article, we show that dietary antioxidants can alternatively switch to a prooxidant action in the presence of transition metals such as copper. Such a prooxidant action leads to strand breaks in cellular DNA and growth inhibition in cancer cells. Further, the cellular DNA breakage and anticancer effects were found to be significantly enhanced in the presence of copper ions. Moreover, inhibition of antioxidant-induced DNA strand breaks and oxidative stress by Cu(I)-specific chelators bathocuproine and neocuproine demonstrated the role of endogenous copper in the induction of the prooxidant mechanism. Since it is well established that tissue, cellular, and serum copper levels are considerably elevated in various malignancies, such a prooxidant cytotoxic mechanism better explains the anticancer activity of dietary antioxidants against cancer cells.

  1. Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation

    SciTech Connect

    Yoon, Dong Suk; Choi, Yoorim; Choi, Seong Mi

    2015-11-27

    Resveratrol is a sirtuin 1 (SIRT1) activator and can function as an anti-inflammatory and antioxidant factor. In mesenchymal stem cells (MSCs), resveratrol enhances the proliferation and differentiation potential and has an anti-aging effect. However, contradictory effects of resveratrol on MSC cultures have been reported. In this study, we found that resveratrol had different effects on MSC cultures according to their cell passage and SIRT1 expression. Resveratrol enhanced the self-renewal potential and multipotency of early passage MSCs, but accelerated cellular senescence of late passage MSCs. In early passage MSCs expressing SIRT1, resveratrol decreased ERK and GSK-3β phosphorylation, suppressing β-catenin activity. Inmore » contrast, in late passage MSCs, which did not express SIRT1, resveratrol increased ERK and GSK-3β phosphorylation, activating β-catenin. We confirmed that SIRT1-deficient early passage MSCs treated with resveratrol lost their self-renewal potential and multipotency, and became senescent due to increased β-catenin activity. Sustained treatment with resveratrol at early passages maintained the self-renewal potential and multipotency of MSCs up to passage 10. Our findings suggest that resveratrol can be effectively applied to early passage MSC cultures, whereas parameters such as cell passage and SIRT1 expression must be taken into consideration before applying resveratrol to late passage MSCs. - Highlights: • Resveratrol enhances self-renewal potential and multipotency of early passage MSCs. • Resveratrol accelerates the cellular senescence of late passage MSCs. • The effects of resveratrol on MSCs are dependent on the presence of SIRT1. • SIRT1 modulates ERK/GSK-3β/β-catenin signaling. • Sustained resveratrol treatment maintains MSC stemness up to P10.« less

  2. Combined Effect of Cameo2 and CBP on the Cellular Uptake of Lutein in the Silkworm, Bombyx mori

    PubMed Central

    Dong, Xiao-Long; Chai, Chun-Li; Pan, Cai-Xia; Tang, Hui; Chen, Yan-Hong; Dai, Fang-Yin; Pan, Min-Hui; Lu, Cheng

    2014-01-01

    Formation of yellow-red color cocoons in the silkworm, Bombyx mori, occurs as the result of the selective delivery of carotenoids from the midgut to the silk gland via the hemolymph. This process of pigment transport is thought to be mediated by specific cellular carotenoids carrier proteins. Previous studies indicated that two proteins, Cameo2 and CBP, are associated with the selective transport of lutein from the midgut into the silk gland in Bombyx mori. However, the exact roles of Cameo2 and CBP during the uptake and transport of carotenoids are still unknown. In this study, we investigated the respective contributions of these two proteins to lutein and β-carotene transport in Bombyx mori as well as commercial cell-line. We found that tissues, expressed both Cameo2 and CBP, accumulate lutein. Cells, co-expressed Cameo2 and CBP, absorb 2 fold more lutein (P<0.01) than any other transfected cells, and the rate of cellular uptake of lutein was concentration-dependent and reached saturation. From immunofluorescence staining, confocal microscopy observation and western blot analysis, Cameo2 was localized at the membrane and CBP was expressed in the cytosol. What’s more, bimolecular fluorescence complementation analysis showed that these two proteins directly interacted at cellular level. Therefore, Cameo2 and CBP are necessarily expressed in midguts and silk glands for lutein uptake in Bombyx mori. Cameo2 and CBP, as the membrane protein and the cytosol protein, respectively, have the combined effect to facilitate the cellular uptake of lutein. PMID:24475153

  3. Effect of molecular characteristics on cellular uptake, subcellular localization, and phototoxicity of Zn(II) N-alkylpyridylporphyrins.

    PubMed

    Ezzeddine, Rima; Al-Banaw, Anwar; Tovmasyan, Artak; Craik, James D; Batinic-Haberle, Ines; Benov, Ludmil T

    2013-12-20

    Tetra-cationic Zn(II) meso-tetrakis(N-alkylpyridinium-2 (or -3 or -4)-yl)porphyrins (ZnPs) with progressively increased lipophilicity were synthesized to investigate how the tri-dimensional shape and lipophilicity of the photosensitizer (PS) affect cellular uptake, subcellular distribution, and photodynamic efficacy. The effect of the tri-dimensional shape of the molecule was studied by shifting the N-alkyl substituent attached to the pyridyl nitrogen from ortho to meta and para positions. Progressive increase of lipophilicity from shorter hydrophilic (methyl) to longer amphiphilic (hexyl) alkyl chains increased the phototoxicity of the ZnP PSs. PS efficacy was also increased for all derivatives when the alkyl substituents were shifted from ortho to meta, and from meta to para positions. Both cellular uptake and subcellular distribution of the PSs were affected by the lipophilicity and the position of the alkyl chains on the periphery of the porphyrin ring. Whereas the hydrophilic ZnPs demonstrated mostly lysosomal distribution, the amphiphilic hexyl derivatives were associated with mitochondria, endoplasmic reticulum, and plasma membrane. A comparison of hexyl isomers revealed that cellular uptake and partition into membranes followed the order para > meta > ortho. Varying the position and length of the alkyl substituents affects (i) the exposure of cationic charges for electrostatic interactions with anionic biomolecules and (ii) the lipophilicity of the molecule. The charge, lipophilicity, and the tri-dimensional shape of the PS are the major factors that determine cellular uptake, subcellular distribution, and as a consequence, the phototoxicity of the PSs.

  4. Effect of Molecular Characteristics on Cellular Uptake, Subcellular Localization, and Phototoxicity of Zn(II) N-Alkylpyridylporphyrins*

    PubMed Central

    Ezzeddine, Rima; Al-Banaw, Anwar; Tovmasyan, Artak; Craik, James D.; Batinic-Haberle, Ines; Benov, Ludmil T.

    2013-01-01

    Tetra-cationic Zn(II) meso-tetrakis(N-alkylpyridinium-2 (or -3 or -4)-yl)porphyrins (ZnPs) with progressively increased lipophilicity were synthesized to investigate how the tri-dimensional shape and lipophilicity of the photosensitizer (PS) affect cellular uptake, subcellular distribution, and photodynamic efficacy. The effect of the tri-dimensional shape of the molecule was studied by shifting the N-alkyl substituent attached to the pyridyl nitrogen from ortho to meta and para positions. Progressive increase of lipophilicity from shorter hydrophilic (methyl) to longer amphiphilic (hexyl) alkyl chains increased the phototoxicity of the ZnP PSs. PS efficacy was also increased for all derivatives when the alkyl substituents were shifted from ortho to meta, and from meta to para positions. Both cellular uptake and subcellular distribution of the PSs were affected by the lipophilicity and the position of the alkyl chains on the periphery of the porphyrin ring. Whereas the hydrophilic ZnPs demonstrated mostly lysosomal distribution, the amphiphilic hexyl derivatives were associated with mitochondria, endoplasmic reticulum, and plasma membrane. A comparison of hexyl isomers revealed that cellular uptake and partition into membranes followed the order para > meta > ortho. Varying the position and length of the alkyl substituents affects (i) the exposure of cationic charges for electrostatic interactions with anionic biomolecules and (ii) the lipophilicity of the molecule. The charge, lipophilicity, and the tri-dimensional shape of the PS are the major factors that determine cellular uptake, subcellular distribution, and as a consequence, the phototoxicity of the PSs. PMID:24214973

  5. Early histological and functional effects of chronic copper exposure in rat liver.

    PubMed

    Cisternas, Felipe A; Tapia, Gladys; Arredondo, Miguel; Cartier-Ugarte, Denise; Romanque, Pamela; Sierralta, Walter D; Vial, María T; Videla, Luis A; Araya, Magdalena

    2005-10-01

    Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1,200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.

  6. Effects of seawater acidification on the early development of sea urchin Glyptocidaris crenularis

    NASA Astrophysics Data System (ADS)

    Zhan, Yaoyao; Hu, Wanbin; Duan, Lizhu; Liu, Minbo; Zhang, Weijie; Chang, Yaqing; Li, Cong

    2017-10-01

    In this study, we evaluated the effects of CO2-induced seawater acidification on fertilization, embryogenesis and early larval development in the sea urchin Glyptocidaris crenularis, that inhabits subtidal coastal areas in northern China. The range in seawater pH used in experiments was based on the projections of the Intergovernmental Panel on Climate Change (IPCC), to the year 2100. A natural seawater treatment (pHnbs=7.98±0.03) and three laboratory-controlled acidified treatments (OA1, ΔpHnbs=-0.3 units; OA2, ΔpHnbs=-0.4 units; OA3, ΔpHnbs=-0.5 units) were used in experiments. Results show that: (1) there was a negative effect of seawater acidification on fertilization and on the percentage of abnormal fertilized eggs; (2) the size of early cleavage stage embryos decreased in a dose-dependent manner with decreasing pH; (3) both the hatching rate of blastulae and the survival rate of four-armed pluteus larvae decreased as pH declined; (4) larval abnormalities including asymmetrical development, changes in the length of skeletal elements, and corroded spicules were observed in all seawater acidified-treatments compared with the control. These data indicate that seawater acidification has a negative impact on the early development of G. crenularis, and supports the hypothesis that the response of echinoderms to ocean acidification (OA) varies among species. Further research is required to clarify the specific cellular mechanisms involved.

  7. Epoxy-functionalized mesostructured cellular foams as effective support for covalent immobilization of penicillin G acylase

    NASA Astrophysics Data System (ADS)

    Xue, Ping; Xu, Fang; Xu, Lidong

    2008-12-01

    The epoxy-functionalized mesoporous cellular foams (G-MCFs) with high specific surface area (˜400 m 2/g) and large-size mesopores (˜17 nm) were obtained by condensation of 3-glycidoxypropyltriethoxysilane (GPTS) and the surface silanol groups of mesoporous cellular foams (MCFs) and used as the support for immobilization of penicillin G acylase (PGA). The structural properties of G-MCF were characterized by FT-IR, N 2 adsorption, TG-DTA and 29Si MAS NMR. The studies indicated that the glycidoxypropyl groups were chemically bonded to the silicon atoms on the surface of MCF. The epoxy-functionalized mesoporous cellular foams can provide the microenvironments suitable for the immobilization of PGA, and the enzyme molecules could be immobilized covalently onto the G-MCF under mild conditions by reaction between the amino groups of the enzyme molecules and the epoxy groups on the surface of G-MCF. The PGA immobilized on G-MCF (PGA/G-MCF) exhibited the apparent activity of 1782 IU/g and 46.6% of activity recovery for hydrolyzing penicillin G potassium to produce 6-aminopenicillanic acid at 37 °C which were higher than that of PGA on pure silica MCF (1521 IU/g and 39.8%, respectively). The kinetic study also indicated that PGA immobilized on G-MCF has a Km of 2.1 × 10 -2 mol/L lower than that of PGA immobilized on the pure silica MCF (5.0 × 10 -2 mol/L). These may be attributed to the enhanced surface affinity between G-MCF support and the substrate molecules. Due to the covalent immobilization of PGA molecules on the surface of G-MCF, the immobilized PGA with considerable operational stability was achieved. The activity of PGA/G-MCF is still about 91.4% of its initial activity at the 10th cycle reuse while that of PGA/MCF only remains 41.5% of its initial activity at the same reuse numbers. In addition, the investigation results show the thermal stability and durability on acid or basic medium of PGA immobilized on G-MCF were improved remarkably.

  8. Cellular automaton simulation examining progenitor hierarchy structure effects on mammary ductal carcinoma in situ.

    PubMed

    Bankhead, Armand; Magnuson, Nancy S; Heckendorn, Robert B

    2007-06-07

    A computer simulation is used to model ductal carcinoma in situ, a form of non-invasive breast cancer. The simulation uses known histological morphology, cell types, and stochastic cell proliferation to evolve tumorous growth within a duct. The ductal simulation is based on a hybrid cellular automaton design using genetic rules to determine each cell's behavior. The genetic rules are a mutable abstraction that demonstrate genetic heterogeneity in a population. Our goal was to examine the role (if any) that recently discovered mammary stem cell hierarchies play in genetic heterogeneity, DCIS initiation and aggressiveness. Results show that simpler progenitor hierarchies result in greater genetic heterogeneity and evolve DCIS significantly faster. However, the more complex progenitor hierarchy structure was able to sustain the rapid reproduction of a cancer cell population for longer periods of time.

  9. Effects of salinity on the cellular physiological responses of Natrinema sp. J7-2

    PubMed Central

    Mei, Yunjun; Liu, Huan; Zhang, Shunxi; Yang, Ming; Hu, Chun; Zhang, Jian; Shen, Ping; Chen, Xiangdong

    2017-01-01

    The halophilic archaea (haloarchaea) live in hyersaline environments such as salt lakes, salt ponds and marine salterns. To cope with the salt stress conditions, haloarchaea have developed two fundamentally different strategies: the "salt-in" strategy and the "compatible-solute" strategy. Although investigation of the molecular mechanisms underlying the tolerance to high salt concentrations has made outstanding achievements, experimental study from the aspect of transcription is rare. In the present study, we monitored cellular physiology of Natrinema sp. J7-2 cells incubated in different salinity media (15%, 25% and 30% NaCl) from several aspects, such as cellular morphology, growth, global transcriptome and the content of intracellular free amino acids. The results showed that the cells were polymorphic and fragile at a low salt concentration (15% NaCl) but had a long, slender rod shape at high salt concentrations (25% and 30% NaCl). The cells grew best in 25% NaCl, mediocre in 30% NaCl and struggled in 15% NaCl. An RNA-seq analysis revealed differentially expressed genes (DEGs) in various salinity media. A total of 1,148 genes were differentially expressed, consisting of 719 DEGs (348 up-regulated and 371 down-regulated genes) between cells in 15% vs 25% NaCl, and 733 DEGs (521 up-regulated and 212 down-regulated genes) between cells in 25% vs 30% NaCl. Moreover, 304 genes were commonly differentially expressed in both 15% vs 25% and 25% vs30% NaCl. The DEGs were enriched in different KEGG metabolic pathways, such as amino acids, glycerolipid, ribosome, nitrogen, protoporphyrin, porphyrin and porhiniods. The intracellular predominant free amino acids consisted of the glutamate family (Glu, Arg and Pro), aspartate family (Asp) and aromatic amino acids (Phe and Trp), especially Glu and Asp. PMID:28926633

  10. Static Magnetic Field Exposure Reproduces Cellular Effects of the Parkinson's Disease Drug Candidate ZM241385

    PubMed Central

    Wang, Zhiyun; Che, Pao-Lin; Du, Jian; Ha, Barbara; Yarema, Kevin J.

    2010-01-01

    Background This study was inspired by coalescing evidence that magnetic therapy may be a viable treatment option for certain diseases. This premise is based on the ability of moderate strength fields (i.e., 0.1 to 1 Tesla) to alter the biophysical properties of lipid bilayers and in turn modulate cellular signaling pathways. In particular, previous results from our laboratory (Wang et al., BMC Genomics, 10, 356 (2009)) established that moderate strength static magnetic field (SMF) exposure altered cellular endpoints associated with neuronal function and differentiation. Building on this background, the current paper investigated SMF by focusing on the adenosine A2A receptor (A2AR) in the PC12 rat adrenal pheochromocytoma cell line that displays metabolic features of Parkinson's disease (PD). Methodology and Principal Findings SMF reproduced several responses elicited by ZM241385, a selective A2AR antagonist, in PC12 cells including altered calcium flux, increased ATP levels, reduced cAMP levels, reduced nitric oxide production, reduced p44/42 MAPK phosphorylation, inhibited proliferation, and reduced iron uptake. SMF also counteracted several PD-relevant endpoints exacerbated by A2AR agonist CGS21680 in a manner similar to ZM241385; these include reduction of increased expression of A2AR, reversal of altered calcium efflux, dampening of increased adenosine production, reduction of enhanced proliferation and associated p44/42 MAPK phosphorylation, and inhibition of neurite outgrowth. Conclusions and Significance When measured against multiple endpoints, SMF elicited qualitatively similar responses as ZM241385, a PD drug candidate. Provided that the in vitro results presented in this paper apply in vivo, SMF holds promise as an intriguing non-invasive approach to treat PD and potentially other neurological disorders. PMID:21079735

  11. Delineating the Tes Interaction Site in Zyxin and Studying Cellular Effects of Its Disruption.

    PubMed

    Hadzic, Ermin; Catillon, Marie; Halavatyi, Aliaksandr; Medves, Sandrine; Van Troys, Marleen; Moes, Michèle; Baird, Michelle A; Davidson, Michael W; Schaffner-Reckinger, Elisabeth; Ampe, Christophe; Friederich, Evelyne

    2015-01-01

    Focal adhesions are integrin-based structures that link the actin cytoskeleton and the extracellular matrix. They play an important role in various cellular functions such as cell signaling, cell motility and cell shape. To ensure and fine tune these different cellular functions, adhesions are regulated by a large number of proteins. The LIM domain protein zyxin localizes to focal adhesions where it participates in the regulation of the actin cytoskeleton. Because of its interactions with a variety of binding partners, zyxin has been proposed to act as a molecular scaffold. Here, we studied the interaction of zyxin with such a partner: Tes. Similar to zyxin, Tes harbors three highly conserved LIM domains of which the LIM1 domain directly interacts with zyxin. Using different zyxin variants in pull-down assays and ectopic recruitment experiments, we identified the Tes binding site in zyxin and showed that four highly conserved amino acids are crucial for its interaction with Tes. Based upon these findings, we used a zyxin mutant defective in Tes-binding to assess the functional consequences of abrogating the zyxin-Tes interaction in focal adhesions. Performing fluorescence recovery after photobleaching, we showed that zyxin recruits Tes to focal adhesions and modulates its turnover in these structures. However, we also provide evidence for zyxin-independent localization of Tes to focal adhesions. Zyxin increases focal adhesion numbers and reduces focal adhesion lifetimes, but does so independent of Tes. Quantitative analysis showed that the loss of interaction between zyxin and Tes affects the process of cell spreading. We conclude that zyxin influences focal adhesion dynamics, that it recruits Tes and that this interaction is functional in regulating cell spreading.

  12. Cellular automata simulation of topological effects on the dynamics of feed-forward motifs

    PubMed Central

    Apte, Advait A; Cain, John W; Bonchev, Danail G; Fong, Stephen S

    2008-01-01

    Background Feed-forward motifs are important functional modules in biological and other complex networks. The functionality of feed-forward motifs and other network motifs is largely dictated by the connectivity of the individual network components. While studies on the dynamics of motifs and networks are usually devoted to the temporal or spatial description of processes, this study focuses on the relationship between the specific architecture and the overall rate of the processes of the feed-forward family of motifs, including double and triple feed-forward loops. The search for the most efficient network architecture could be of particular interest for regulatory or signaling pathways in biology, as well as in computational and communication systems. Results Feed-forward motif dynamics were studied using cellular automata and compared with differential equation modeling. The number of cellular automata iterations needed for a 100% conversion of a substrate into a target product was used as an inverse measure of the transformation rate. Several basic topological patterns were identified that order the specific feed-forward constructions according to the rate of dynamics they enable. At the same number of network nodes and constant other parameters, the bi-parallel and tri-parallel motifs provide higher network efficacy than single feed-forward motifs. Additionally, a topological property of isodynamicity was identified for feed-forward motifs where different network architectures resulted in the same overall rate of the target production. Conclusion It was shown for classes of structural motifs with feed-forward architecture that network topology affects the overall rate of a process in a quantitatively predictable manner. These fundamental results can be used as a basis for simulating larger networks as combinations of smaller network modules with implications on studying synthetic gene circuits, small regulatory systems, and eventually dynamic whole-cell models

  13. Delineating the Tes Interaction Site in Zyxin and Studying Cellular Effects of Its Disruption

    PubMed Central

    Hadzic, Ermin; Catillon, Marie; Halavatyi, Aliaksandr; Medves, Sandrine; Van Troys, Marleen; Moes, Michèle; Baird, Michelle A.; Davidson, Michael W.; Schaffner-Reckinger, Elisabeth; Ampe, Christophe; Friederich, Evelyne

    2015-01-01

    Focal adhesions are integrin-based structures that link the actin cytoskeleton and the extracellular matrix. They play an important role in various cellular functions such as cell signaling, cell motility and cell shape. To ensure and fine tune these different cellular functions, adhesions are regulated by a large number of proteins. The LIM domain protein zyxin localizes to focal adhesions where it participates in the regulation of the actin cytoskeleton. Because of its interactions with a variety of binding partners, zyxin has been proposed to act as a molecular scaffold. Here, we studied the interaction of zyxin with such a partner: Tes. Similar to zyxin, Tes harbors three highly conserved LIM domains of which the LIM1 domain directly interacts with zyxin. Using different zyxin variants in pull-down assays and ectopic recruitment experiments, we identified the Tes binding site in zyxin and showed that four highly conserved amino acids are crucial for its interaction with Tes. Based upon these findings, we used a zyxin mutant defective in Tes-binding to assess the functional consequences of abrogating the zyxin-Tes interaction in focal adhesions. Performing fluorescence recovery after photobleaching, we showed that zyxin recruits Tes to focal adhesions and modulates its turnover in these structures. However, we also provide evidence for zyxin-independent localization of Tes to focal adhesions. Zyxin increases focal adhesion numbers and reduces focal adhesion lifetimes, but does so independent of Tes. Quantitative analysis showed that the loss of interaction between zyxin and Tes affects the process of cell spreading. We conclude that zyxin influences focal adhesion dynamics, that it recruits Tes and that this interaction is functional in regulating cell spreading. PMID:26509500

  14. High Severity Wildfire Effect On Rainfall Infiltration And Runoff: A Cellular Automata Based Simulation

    NASA Astrophysics Data System (ADS)

    Vergara-Blanco, J. E.; Leboeuf-Pasquier, J.; Benavides-Solorio, J. D. D.

    2017-12-01

    A simulation software that reproduces rainfall infiltration and runoff for a storm event in a particular forest area is presented. A cellular automaton is utilized to represent space and time. On the time scale, the simulation is composed by a sequence of discrete time steps. On the space scale, the simulation is composed of forest surface cells. The software takes into consideration rain intensity and length, individual forest cell soil absorption capacity evolution, and surface angle of inclination. The software is developed with the C++ programming language. The simulation is executed on a 100 ha area within La Primavera Forest in Jalisco, Mexico. Real soil texture for unburned terrain and high severity wildfire affected terrain is employed to recreate the specific infiltration profile. Historical rainfall data of a 92 minute event is used. The Horton infiltration equation is utilized for infiltration capacity calculation. A Digital Elevation Model (DEM) is employed to reproduce the surface topography. The DEM is displayed with a 3D mesh graph where individual surface cells can be observed. The plot colouring renders water content development at the cell level throughout the storm event. The simulation shows that the cumulative infiltration and runoff which take place at the surface cell level depend on the specific storm intensity, fluctuation and length, overall terrain topography, cell slope, and soil texture. Rainfall cumulative infiltration for unburned and high severity wildfire terrain are compared: unburned terrain exhibits a significantly higher amount of rainfall infiltration.It is concluded that a cellular automaton can be utilized with a C++ program to reproduce rainfall infiltration and runoff under diverse soil texture, topographic and rainfall conditions in a forest setting. This simulation is geared for an optimization program to pinpoint the locations of a series of forest land remediation efforts to support reforestation or to minimize runoff.

  15. Impulsive effect on global exponential stability of BAM fuzzy cellular neural networks with time-varying delays

    NASA Astrophysics Data System (ADS)

    Li, Kelin

    2010-02-01

    In this article, a class of impulsive bidirectional associative memory (BAM) fuzzy cellular neural networks (FCNNs) with time-varying delays is formulated and investigated. By employing delay differential inequality and M-matrix theory, some sufficient conditions ensuring the existence, uniqueness and global exponential stability of equilibrium point for impulsive BAM FCNNs with time-varying delays are obtained. In particular, a precise estimate of the exponential convergence rate is also provided, which depends on system parameters and impulsive perturbation intention. It is believed that these results are significant and useful for the design and applications of BAM FCNNs. An example is given to show the effectiveness of the results obtained here.

  16. Manifestation of the shape-memory effect in polyetherurethane cellular plastics, fabric composites, and sandwich structures under microgravity

    NASA Astrophysics Data System (ADS)

    Babaevskii, P. G.; Kozlov, N. A.; Agapov, I. G.; Reznichenko, G. M.; Churilo, N. V.; Churilo, I. V.

    2016-09-01

    The results of experiments that were performed to test the feasibility of creating sandwich structures (consisting of thin-layer sheaths of polymer composites and a cellular polymer core) with the shapememory effect as models of the transformable components of space structures have been given. The data obtained indicate that samples of sandwich structures under microgravity conditions on board the International Space Station have recovered their shape to almost the same degree as under terrestrial conditions, which makes it possible to recommend them for creating components of transformable space structures on their basis.

  17. A Fork in the Road: The Effects of Different Cellular Pathways on Melanoma | Center for Cancer Research

    Cancer.gov

    Malignant melanoma is one of the most deadly forms of cancer because of its high capacity to metastasize and because there are few treatments effective in stopping its progression. The extensive body of research on melanoma has identified several important protein mutations that contribute to development of the disease. One of these proteins, Ras, is mutated in 25 percent of cutaneous malignant melanomas. These mutations disrupt Ras regulation, switching the protein permanently "on," leading to constant signaling of cellular messengers and stimulating growth without normal checks and balances.

  18. Protective effect of an intrinsic antioxidant, HMH (5-hydroxy-1-methylhydantoin; NZ-419), against cellular damage of kidney tubules.

    PubMed

    Ienaga, Kazuharu; Park, Chan Hum; Yokozawa, Takako

    2013-07-01

    HMH (5-hydroxy-1-methylhydantoin; NZ-419) is a mammalian creatinine metabolite and an intrinsic antioxidant. HMH prevents the progression of chronic kidney disease in rats when a sufficient amount is taken orally. We assessed whether intrinsic and higher levels of HMH could protect tubular epithelial cells, LLC-PK(1) cells, against known cellular damage caused by xenobiotics, such as cisplatin and cephaloridine, or by hypoxia/reoxygenation treatment. Both cell damage and peroxidation, monitored as the leakage of lactate dehydrogenase (LDH) and malondialdehyde (MDA), respectively, from cells into the media, were inhibited by HMH in a concentration-dependent manner. The minimum effective concentration of HMH (2.5 μM) seemed to be too low for HMH to only be a direct hydroxyl radical scavenger. Additional antioxidant effect(s) inhibiting reactive oxygen species generation and/or modulating signal transduction pathways were suggested. The possibility that intrinsic HMH could be a protectant for the kidney was indicated. At the same time, for sufficient inhibition, higher concentrations than intrinsic HMH concentrations may be necessary. Patterns of efficacies of HMH on LDH and MDA against different kinds of cellular damage were compared with our reported data on those of corresponding, naturally occurring antioxidants. A common and specific inhibitory mechanism as well as common target(s) in kidney injuries were indicated. Copyright © 2012 Elsevier GmbH. All rights reserved.

  19. Ag Nanoparticles (Ag NM300K) in the Terrestrial Environment: Effects at Population and Cellular Level in Folsomia candida (Collembola)

    PubMed Central

    Mendes, Luís André; Maria, Vera L.; Scott-Fordsmand, Janeck J.; Amorim, Mónica J. B.

    2015-01-01

    The effects of nanomaterials have been primarily assessed based on standard ecotoxicity guidelines. However, by adapting alternative measures the information gained could be enhanced considerably, e.g., studies should focus on more mechanistic approaches. Here, the environmental risk posed by the presence of silver nanoparticles (Ag NM300K) in soil was investigated, anchoring population and cellular level effects, i.e., survival, reproduction (28 days) and oxidative stress markers (0, 2, 4, 6, 10 days). The standard species Folsomia candida was used. Measured markers included catalase (CAT), glutathione reductase (GR), glutathione S-transferase (GST), total glutathione (TG), metallothionein (MT) and lipid peroxidation (LPO). Results showed that AgNO3 was more toxic than AgNPs at the population level: reproduction EC20 and EC50 was ca. 2 and 4 times lower, respectively. At the cellular level Correspondence Analysis showed a clear separation between AgNO3 and AgNP throughout time. Results showed differences in the mechanisms, indicating a combined effect of released Ag+ (MT and GST) and of AgNPs (CAT, GR, TG, LPO). Hence, clear advantages from mechanistic approaches are shown, but also that time is of importance when measuring such responses. PMID:26473892

  20. Understanding the effect of alkyl chains of gemini cations on the physicochemical and cellular properties of polyurethane micelles.

    PubMed

    Pan, Zhicheng; Fang, Danxuan; Song, Yuanqing; Song, Nijia; Ding, Mingming; Li, Jiehua; Luo, Feng; Li, Jianshu; Tan, Hong; Fu, Qiang

    2018-06-06

    Cationic gemini quaternary ammonium (GQA) has been used as a cell internalization promoter to improve the permeability of the cell membrane and enhance the cellular uptake. However, the effect of the alkyl chain length on the cellular properties of nanocarriers has not been elucidated yet. In this study, we developed a series of polyurethane micelles containing GQAs with various alkyl chain lengths. The alteration of the gemini alkyl chain length was found to change the distribution of GQA surfactants in the micellar structure and affect the surface charge exposure, stability, and the protein absorption properties of nanocarriers. Moreover, we also clarified the role of the alkyl chain length in tumor cell internalization and macrophage uptake of polyurethane micelles. This work provides a new understanding on the effect of the GQA alkyl chain length on the physicochemical and biological properties of nanomedicines, and offers guidance on the rational design of effective drug delivery systems where the issue of functional group exposure at the micellar surface should be considered.

  1. A Cost-Effectiveness Analysis of Early Literacy Interventions

    ERIC Educational Resources Information Center

    Simon, Jessica

    2011-01-01

    Success in early literacy activities is associated with improved educational outcomes, including reduced dropout risk, in-grade retention, and special education referrals. When considering programs that will work for a particular school and context; cost-effectiveness analysis may provide useful information for decision makers. The study…

  2. Effects of Progress Monitoring Feedback on Early Literacy Student Achievement

    ERIC Educational Resources Information Center

    Lopuch, Jeremy Jon

    2016-01-01

    The purpose of this study was to examine the effects of diagnostic formative assessment feedback on early literacy skills. The participants were 12 first-grade general education teachers and 51 of their students who were assigned to the following treatments, diagnostic feedback and skills feedback (control) which lasted for 10 weeks. During the…

  3. Effect of a Targeted Early Literacy Intervention for English Learners

    ERIC Educational Resources Information Center

    Arellano, Elizabeth Michelle

    2013-01-01

    This study examined the effectiveness of a targeted early literacy intervention among Spanish-speaking kindergarten English Learners (ELs). Using a Response to Intervention (RtI) framework, participants were screened in English to ensure a need for additional literacy support. Selected students were then screened in Spanish, and students with…

  4. Boosting Early Development: The Mixed Effects of Kindergarten Enrollment Age

    ERIC Educational Resources Information Center

    Zhang, Jiahui; Xin, Tao

    2012-01-01

    This study aimed to investigate the effects of kindergarten enrollment age on four-year-old Chinese children's early cognition and problem behavior using multilevel models. The sample comprised of 1,391 pre-school children (the mean age is 4.58 years old) from 74 kindergartens in six different provinces. The results demonstrated curvilinear…

  5. Longitudinal Effects on Early Adolescent Language: A Twin Study

    ERIC Educational Resources Information Center

    Harlarr, Nicole; De Thorne, Laura Segebart; Smith, Jamie Mahurin; Betancourt, Mariana Aparicio; Petrill, Stephen A.

    2016-01-01

    Purpose: We evaluated genetic and environmental contributions to individual differences in language skills during early adolescence, measured by both language sampling and standardized tests, and examined the extent to which these genetic and environmental effects are stable across time. Purpose: We evaluated genetic and environmental…

  6. Spatial Working Memory Effects in Early Visual Cortex

    ERIC Educational Resources Information Center

    Munneke, Jaap; Heslenfeld, Dirk J.; Theeuwes, Jan

    2010-01-01

    The present study investigated how spatial working memory recruits early visual cortex. Participants were required to maintain a location in working memory while changes in blood oxygen level dependent (BOLD) signals were measured during the retention interval in which no visual stimulation was present. We show working memory effects during the…

  7. The Effectiveness of Early Foreign Language Learning in the Netherlands

    ERIC Educational Resources Information Center

    de Bot, Kees

    2014-01-01

    This article reports on a number of projects on early English teaching in the Netherlands. The focus of these projects has been on the impact of English on the development of the mother tongue and the development of skills in the foreign language. Overall the results show that there is no negative effect on the mother tongue and that the gains in…

  8. ATRAZINE EFFECTS ON EARLY PREGNANCY AND IMPLANATION IN THE RAT

    EPA Science Inventory

    Atrazine Effects on Early Pregnancy and Implantation in the Rat.
    A.M. Cummings, B.E. Rhodes*, and R.L. Cooper*.
    Reproductive Toxicology Division, NHEERL, USEPA, Research Triangle Park, NC
    Atrazine (ATR), an herbicide, can induce mammary tumors in rats. ATR can also sup...

  9. HIV Infection: Transmission, Effects on Early Development, and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1997-01-01

    Describes the modes of transmission of HIV and the course of the disease in infants and toddlers. Information is provided on its effects on early development, medical screening and treatments, therapies, psychosocial assistance, and interventions, including nutritional therapy, occupational and physical therapies, and speech and language therapy.…

  10. Effects of Nerve Injury and Segmental Regeneration on the Cellular Correlates of Neural Morphallaxis

    PubMed Central

    Martinez, Veronica G.; Manson, Josiah M.B.; Zoran, Mark J.

    2009-01-01

    Functional recovery of neural networks after injury requires a series of signaling events similar to the embryonic processes that governed initial network construction. Neural morphallaxis, a form of nervous system regeneration, involves reorganization of adult neural connectivity patterns. Neural morphallaxis in the worm, Lumbriculus variegatus, occurs during asexual reproduction and segmental regeneration, as body fragments acquire new positional identities along the anterior–posterior axis. Ectopic head (EH) formation, induced by ventral nerve cord lesion, generated morphallactic plasticity including the reorganization of interneuronal sensory fields and the induction of a molecular marker of neural morphallaxis. Morphallactic changes occurred only in segments posterior to an EH. Neither EH formation, nor neural morphallaxis was observed after dorsal body lesions, indicating a role for nerve cord injury in morphallaxis induction. Furthermore, a hierarchical system of neurobehavioral control was observed, where anterior heads were dominant and an EH controlled body movements only in the absence of the anterior head. Both suppression of segmental regeneration and blockade of asexual fission, after treatment with boric acid, disrupted the maintenance of neural morphallaxis, but did not block its induction. Therefore, segmental regeneration (i.e., epimorphosis) may not be required for the induction of morphallactic remodeling of neural networks. However, on-going epimorphosis appears necessary for the long-term consolidation of cellular and molecular mechanisms underlying the morphallaxis of neural circuitry. PMID:18561185

  11. Effects of multiple enzyme-substrate interactions in basic units of cellular signal processing

    NASA Astrophysics Data System (ADS)

    Seaton, D. D.; Krishnan, J.

    2012-08-01

    Covalent modification cycles are a ubiquitous feature of cellular signalling networks. In these systems, the interaction of an active enzyme with the unmodified form of its substrate is essential for signalling to occur. However, this interaction is not necessarily the only enzyme-substrate interaction possible. In this paper, we analyse the behaviour of a basic model of signalling in which additional, non-essential enzyme-substrate interactions are possible. These interactions include those between the inactive form of an enzyme and its substrate, and between the active form of an enzyme and its product. We find that these additional interactions can result in increased sensitivity and biphasic responses, respectively. The dynamics of the responses are also significantly altered by the presence of additional interactions. Finally, we evaluate the consequences of these interactions in two variations of our basic model, involving double modification of substrate and scaffold-mediated signalling, respectively. We conclude that the molecular details of protein-protein interactions are important in determining the signalling properties of enzymatic signalling pathways.

  12. The effects of aggregation and protein corona on the cellular internalization of iron oxide nanoparticles.

    PubMed

    Safi, M; Courtois, J; Seigneuret, M; Conjeaud, H; Berret, J-F

    2011-12-01

    Engineered inorganic nanoparticles are essential components in the development of nanotechnologies. For applications in nanomedicine, particles need to be functionalized to ensure a good dispersibility in biological fluids. In many cases however, functionalization is not sufficient: the particles become either coated by a corona of serum proteins or precipitate out of the solvent. In the present paper, we show that by changing the coating of iron oxide nanoparticles from a low-molecular weight ligand (citrate ions) to small carboxylated polymers (poly(acrylic acid)), the colloidal stability of the dispersion is improved and the adsorption/internalization of iron toward living mammalian cells is profoundly affected. Citrate-coated particles are shown to destabilize in all fetal-calf-serum based physiological conditions tested, whereas the polymer coated particles exhibit an outstanding dispersibility as well as a structure devoid of protein corona. The interactions between nanoparticles and human lymphoblastoid cells are investigated by transmission electron microscopy and flow cytometry. Two types of nanoparticle/cell interactions are underlined. Iron oxides are found either adsorbed on the cellular membranes, or internalized into membrane-bound endocytosis compartments. For the precipitating citrate-coated particles, the kinetics of interactions reveal a massive and rapid adsorption of iron oxide on the cell surfaces. The quantification of the partition between adsorbed and internalized iron was performed from the cytometry data. The results highlight the importance of resilient adsorbed nanomaterials at the cytoplasmic membrane. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Characteristics of effective professional development for early career science teachers

    NASA Astrophysics Data System (ADS)

    Simon, Shirley; Campbell, Sandra; Johnson, Sally; Stylianidou, Fani

    2011-04-01

    The research reported here set out to investigate the features in schools and science departments that were seen as effective in contributing to the continuing professional development (CPD) of early career science teachers. Ten schools took part in the study, selected on the basis of their reputation for having effective CPD practices. To gain different perspectives from within the organisations we conducted interviews with senior members of staff, heads of science departments and early career teachers. A thematic analysis of the interviews is presented, drawing on findings from across the 10 schools, and exemplified in more detail by a vignette to show specific features of effective CPD practice. The study has revealed a wealth of practice across the 10 schools, which included a focus on broadening experience beyond the classroom, having an open, sharing, non-threatening culture and systemic procedures for mentoring and support that involved ring-fenced budgets. The schools also deployed staff judiciously in critical roles that model practice and motivate early career science teachers. Early career teachers were concerned primarily with their overall development as teachers, though some science specific examples such as observing practical work and sessions to address subject knowledge were seen as important.

  14. Cellular glucose-6-phosphate dehydrogenase (G6PD) status modulates the effects of nitric oxide (NO) on human foreskin fibroblasts.

    PubMed

    Cheng, M L; Ho, H Y; Liang, C M; Chou, Y H; Stern, A; Lu, F J; Chiu, D T

    2000-06-23

    Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in cellular redox homeostasis, which is crucial for cell survival. In the present study, we found that G6PD status determines the response of cells exposed to nitric oxide (NO) donor. Treatment with NO donor, sodium nitroprusside (SNP), caused apoptosis in G6PD-deficient human foreskin fibroblasts (HFF1), whereas it was growth stimulatory in the normal counterpart (HFF3). Such effects were abolished by NO scavengers like hemoglobin. Ectopic expression of G6PD in HFF1 cells switched the cellular response to NO from apoptosis to growth stimulation. Experiments with 1H-¿1,2,4ŏxadiazolo¿4, 3-aquinoxalin-1-one and 8-bromo-cGMP showed that the effects of NO on HFF1 and HFF3 cells were independent of cGMP signalling pathway. Intriguingly, trolox prevented the SNP-induced apoptosis in HFF1 cells. These data demonstrate that G6PD plays a critical role in regulation of cell growth and survival.

  15. Effects of Nanoparticle Size on Cellular Uptake and Liver MRI with PVP-Coated Iron Oxide Nanoparticles

    PubMed Central

    Huang, Jing; Bu, Lihong; Xie, Jin; Chen, Kai; Cheng, Zhen; Li, Xingguo; Chen, Xiaoyuan

    2010-01-01

    The effect of nanoparticle size (30–120 nm) on magnetic resonance imaging (MRI) of hepatic lesions in vivo has been systematically examined using polyvinylpyrrolidone (PVP)-coated iron oxide nanoparticles (PVP-IOs). Such biocompatible PVP-IOs with different sizes were synthesized by a simple one-pot pyrolysis method. These PVP-IOs exhibited good crystallinity and high T2 relaxivities, and the relaxivity increased with the size of the magnetic nanoparticles. It was found that cellular uptake changed with both size and surface physiochemical properties, and that PVP-IO-37 with a core size of 37 nm and hydrodynamic particle size of 100 nm exhibited higher cellular uptake rate and greater distribution than other PVP-IOs and Feridex. We systematically investigated the effect of nanoparticle size on MRI of normal liver and hepatic lesions in vivo. The physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their ability to accumulate in the liver. The contrast enhancement of PVP-IOs within the liver was highly dependent on the overall size of the nanoparticles, and the 100 nm PVP-IO-37 nanoparticles exhibited the greatest enhancement. These results will have implications in designing engineered nanoparticles that are optimized as MR contrast agents or for use in therapeutics. PMID:21043459

  16. Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes

    PubMed Central

    Samson, Eugenie; Arlia-Ciommo, Anthony; Dakik, Pamela; Cortes, Berly; Feldman, Rachel; Mohtashami, Sadaf; McAuley, Mélissa; Chancharoen, Marisa; Rukundo, Belise; Simard, Éric; Titorenko, Vladimir I.

    2016-01-01

    We discovered six plant extracts that increase yeast chronological lifespan to a significantly greater extent than any of the presently known longevity-extending chemical compounds. One of these extracts is the most potent longevity-extending pharmacological intervention yet described. We show that each of the six plant extracts is a geroprotector which delays the onset and decreases the rate of yeast chronological aging by eliciting a hormetic stress response. We also show that each of these extracts has different effects on cellular processes that define longevity in organisms across phyla. These effects include the following: 1) increased mitochondrial respiration and membrane potential; 2) augmented or reduced concentrations of reactive oxygen species; 3) decreased oxidative damage to cellular proteins, membrane lipids, and mitochondrial and nuclear genomes; 4) enhanced cell resistance to oxidative and thermal stresses; and 5) accelerated degradation of neutral lipids deposited in lipid droplets. Our findings provide new insights into mechanisms through which chemicals extracted from certain plants can slow biological aging. PMID:26918729

  17. Effectiveness of a clinical practice intervention in early rheumatoid arthritis.

    PubMed

    Descalzo, Miguel Ángel; Carbonell, Jordi; González-Álvaro, Isidoro; Sanmartí, Raimon; Balsa, Alejandro; Hernandez-Barrera, Valentín; Román-Ivorra, José Andrés; Ivorra-Cortés, José; Lisbona, Pilar; Alperi, Mercedes; Jiménez-Garcia, Rodrigo; Carmona, Loreto

    2012-03-01

    To compare the outcome of early rheumatoid arthritis (RA) patients in a country where early clinics were established versus the outcome of patients in nonprotocolized clinics. We compared 2 multicenter cohorts: an RA cohort derived from an early arthritis registry set in 36 reference hospitals in which a specific intervention was established (Evaluation of a Model for Arthritis Care in Spain [SERAP]), and a historical control cohort of patients with early RA attending 34 rheumatology departments (Prognosis in Rheumatoid Arthritis [PROAR] cohort). Effectiveness was tested by comparing the change in the Disease Activity Score in 28 joints (DAS28), the change in the Health Assessment Questionnaire (HAQ), and the change in the Sharp/van der Heijde radiologic score using marginal structural models. A total of 161 early RA patients were recruited in the PROAR cohort and 447 in the SERAP cohort. Being a SERAP patient was inversely correlated with activity, resulting in a decrease of -0.24 (95% confidence interval [95% CI] -0.39, -0.08) units in the population average of the DAS28 after adjustment was made. Moreover, intervention may be seen as a protective factor of radiologic damage, with a decrease of -0.05 (95% CI -0.09, -0.01) units in the logarithm of the total Sharp/van der Heijde score. On the other hand, a decrease in functional impairment was detected, but intervention was not statistically associated with HAQ changes. Preventing major radiographic progression in a 2-year term inside structured and organized special programs for the management of disease, such as early arthritis clinics, are effective compared to nonprotocolized referrals, treatment, and followup. Copyright © 2012 by the American College of Rheumatology.

  18. Cellular Contraction and Polarization Drive Collective Cellular Motion.

    PubMed

    Notbohm, Jacob; Banerjee, Shiladitya; Utuje, Kazage J C; Gweon, Bomi; Jang, Hwanseok; Park, Yongdoo; Shin, Jennifer; Butler, James P; Fredberg, Jeffrey J; Marchetti, M Cristina

    2016-06-21

    Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  19. Simulation of land use change and effect on potential deforestation using Markov Chain - Cellular Automata

    NASA Astrophysics Data System (ADS)

    Mujiono, Indra, T. L.; Harmantyo, D.; Rukmana, I. P.; Nadia, Z.

    2017-07-01

    The purpose of this study was to simulate land use change in 1996-2016 and its prediction in 2035 as well as its potential to deforestation. Both of these purposes were obtained through modeling analysis using Markov Chain Cellular Automata. This modeling method was considered important for understanding the causes and impacts. Based on the analysis, the land use change between 1996 to 2007 has caused forest loss (the region and non-region) covering an area of 62,012 ha. While in the period of 2007 to 2016, the change has lead to the east side of the slope grade of 0-15 percent and an altitude between 500-1000 meters above sea level. In this period, plantation area has increased by 50,822 ha, while the forest area has reduced from 80,038 ha. In a period of 20 years, North Bengkulu Regency has lost the forest area of 80,038 ha. The amount of intervention against forest suggested the potential for deforestation in this area. Simulation of land use change in 2035 did not indicate significant deforestation due to the limited land on physical factors such as slope and elevation. However, it should be noted that, in 2035, the area of conservation forest was reduced by 16,793 ha (29 %), while the areas of protected and production forest were reduced by 4,933 ha (19 %) and 2,114 ha (3 %), respectively. Land use change is a serious threat of deforestation, especially in forest areas in North Bengkulu Regency, where any decline in forest area means the addition of plantation area.

  20. Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

    PubMed Central

    Navarro-Zaragoza, Javier; Ros-Simó, Clara; Milanés, María-Victoria; Valverde, Olga; Laorden, María-Luisa

    2015-01-01

    Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone. PMID:26509576

  1. Phytoplankton calcification as an effective mechanism to alleviate cellular calcium poisoning

    NASA Astrophysics Data System (ADS)

    Müller, M. N.; Ramos, J. Barcelos e.; Schulz, K. G.; Riebesell, U.; Kaźmierczak, J.; Gallo, F.; Mackinder, L.; Li, Y.; Nesterenko, P. N.; Trull, T. W.; Hallegraeff, G. M.

    2015-11-01

    Marine phytoplankton have developed the remarkable ability to tightly regulate the concentration of free calcium ions in the intracellular cytosol at a level of ~ 0.1 μmol L-1 in the presence of seawater Ca2+ concentrations of 10 mmol L-1. The low cytosolic calcium ion concentration is of utmost importance for proper cell signalling function. While the regulatory mechanisms responsible for the tight control of intracellular Ca2+ concentration are not completely understood, phytoplankton taxonomic groups appear to have evolved different strategies, which may affect their ability to cope with changes in seawater Ca2+ concentrations in their environment on geological timescales. For example, the Cretaceous (145 to 66 Ma), an era known for the high abundance of coccolithophores and the production of enormous calcium carbonate deposits, exhibited seawater calcium concentrations up to 4 times present-day levels. We show that calcifying coccolithophore species (Emiliania huxleyi, Gephyrocapsa oceanica and Coccolithus braarudii) are able to maintain their relative fitness (in terms of growth rate and photosynthesis) at simulated Cretaceous seawater calcium concentrations, whereas these rates are severely reduced under these conditions in some non-calcareous phytoplankton species (Chaetoceros sp., Ceratoneis closterium and Heterosigma akashiwo). Most notably, this also applies to a non-calcifying strain of E. huxleyi which displays a calcium sensitivity similar to the non-calcareous species. We hypothesize that the process of calcification in coccolithophores provides an efficient mechanism to alleviate cellular calcium poisoning and thereby offered a potential key evolutionary advantage, responsible for the proliferation of coccolithophores during times of high seawater calcium concentrations. The exact function of calcification and the reason behind the highly ornate physical structures of coccoliths remain elusive.

  2. Phytoplankton calcification as an effective mechanism to prevent cellular calcium poisoning

    NASA Astrophysics Data System (ADS)

    Müller, M. N.; Ramos, J. Barcelos e.; Schulz, K. G.; Riebesell, U.; Kaźmierczak, J.; Gallo, F.; Mackinder, L.; Li, Y.; Nesterenko, P. N.; Trull, T. W.; Hallegraeff, G. M.

    2015-08-01

    Marine phytoplankton has developed the remarkable ability to tightly regulate the concentration of free calcium ions in the intracellular cytosol at a level of ~ 0.1 μmol L-1 in the presence of seawater Ca2+ concentrations of 10 mmol L-1. The low cytosolic calcium ion concentration is of utmost importance for proper cell signalling function. While the regulatory mechanisms responsible for the tight control of intracellular Ca2+ concentration are not completely understood, phytoplankton taxonomic groups appear to have evolved different strategies, which may affect their ability to cope with changes in seawater Ca2+ concentrations in their environment on geological time scales. For example, the Cretaceous (145 to 66 Ma ago), an era known for the high abundance of coccolithophores and the production of enormous calcium carbonate deposits, exhibited seawater calcium concentrations up to four times present-day levels. We show that calcifying coccolithophore species (Emiliania huxleyi, Gephyrocapsa oceanica and Coccolithus braarudii) are able to maintain their relative fitness (in terms of growth rate and photosynthesis) at simulated Cretaceous seawater calcium concentrations, whereas these rates are severely reduced under these conditions in some non-calcareous phytoplankton species (Chaetoceros sp., Ceratoneis closterium and Heterosigma akashiwo). Most notably, this also applies to a non-calcifying strain of E. huxleyi which displays a calcium-sensitivity similar to the non-calcareous species. We hypothesize that the process of calcification in coccolithophores provides an efficient mechanism to prevent cellular calcium poisoning and thereby offered a potential key evolutionary advantage, responsible for the proliferation of coccolithophores during times of high seawater calcium concentrations.

  3. Differential effects of subtype-specific nicotinic acetylcholine receptor agonists on early and late hippocampal LTP.

    PubMed

    Kroker, Katja S; Rast, Georg; Rosenbrock, Holger

    2011-12-05

    Brain nicotinic acetylcholine receptors are involved in several neuropsychiatric disorders, e.g. Alzheimer's and Parkinson's diseases, Tourette's syndrome, schizophrenia, depression, autism, attention deficit hyperactivity disorder, and anxiety. Currently, approaches selectively targeting the activation of specific nicotinic acetylcholine receptors are in clinical development for treatment of memory impairment of Alzheimer's disease patients. These are α4β2 and α7 nicotinic acetylcholine receptor agonists which are believed to enhance cholinergic and glutamatergic neurotransmission, respectively. In order to gain a better insight into the mechanistic role of these two nicotinic acetylcholine receptors in learning and memory, we investigated the effects of the α4β2 nicotinic acetylcholine receptor agonist TC-1827 and the α7 nicotinic acetylcholine receptor partial agonist SSR180711 on hippocampal long-term potentiation (LTP), a widely accepted cellular experimental model of memory formation. Generally, LTP is distinguished in an early and a late form, the former being protein-synthesis independent and the latter being protein-synthesis dependent. TC-1827 was found to increase early LTP in a bell-shaped dose dependent manner, but did not affect late LTP. In contrast, the α7 nicotinic acetylcholine receptor partial agonist SSR180711 showed enhancing effects on both early and late LTP in a bell-shaped manner. Furthermore, SSR180711 not only increased early LTP, but also transformed it into late LTP, which was not observed with the α4β2 nicotinic acetylcholine receptor agonist. Therefore, based on these findings α7 nicotinic acetylcholine receptor (partial) agonists appear to exhibit stronger efficacy on memory improvement than α4β2 nicotinic acetylcholine receptor agonists. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy.

    PubMed

    Valdez, Benigno C; Li, Yang; Murray, David; Brammer, Jonathan E; Liu, Yan; Hosing, Chitra; Nieto, Yago; Champlin, Richard E; Andersson, Borje S

    2016-09-27

    HDAC inhibitors, DNA alkylators and nucleoside analogs are effective components of combination chemotherapy. To determine a possible mechanism of their synergism, we analyzed the effects of HDAC inhibitors on the expression of drug transporters which export DNA alkylators. Exposure of PEER lymphoma T-cells to 15 nM romidepsin (Rom) resulted in 40%-50% reduction in mRNA for the drug transporter MRP1 and up to ~500-fold increase in the MDR1 mRNA within 32-48 hrs. MRP1 protein levels concomitantly decreased while MDR1 increased. Other HDAC inhibitors - panobinostat, belinostat and suberoylanilide hydroxamic acid (SAHA) - had similar effects on these transporters. The protein level of MRP1 correlated with cellular resistance to busulfan and chlorambucil, and Rom exposure sensitized cells to these DNA alkylators. The decrease in MRP1 correlated with decreased cellular drug export activity, and increased level of MDR1 correlated with increased export of daunorubicin. A similar decrease in the level of MRP1 protein, and increase in MDR1, were observed when mononuclear cells derived from patients with T-cell malignancies were exposed to Rom. Decreased MRP1 and increased MDR1 expressions were also observed in blood mononuclear cells from lymphoma patients who received SAHA-containing chemotherapy in a clinical trial. This inhibitory effect of HDAC inhibitors on the expression of MRP1 suggests that their synergism with DNA alkylating agents is partly due to decreased efflux of these alkylators. Our results further imply the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy.

  5. Effect of Heat Stress on Reproduction in Dairy Cows: Insights into the Cellular and Molecular Responses of the Oocyte.

    PubMed

    Roth, Zvi

    2017-02-08

    Among the components of the female reproductive tract, the ovarian pool of follicles and their enclosed oocytes are highly sensitive to hyperthermia. Heat-induced alterations in small antral follicles can be expressed later as compromised maturation and developmental capacity of the ovulating oocyte. This review summarizes the most up-to-date information on the effects of heat stress on the oocyte with an emphasis on unclear points and open questions, some of which might involve new research directions, for instance, whether preantral follicles are heat resistant. The review focuses on the follicle-enclosed oocytes, provides new insights into the cellular and molecular responses of the oocyte to elevated temperature, points out the role of the follicle microenvironment, and discusses some mechanisms that might underlie oocyte impairment. Mechanisms include nuclear and cytoplasmic maturation, mitochondrial function, apoptotic pathways, and oxidative stress. Understanding the mechanism by which heat stress compromises fertility might enable development of new strategies to mitigate its effects.

  6. Comparative effect of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction on antioxidant enzymes activity in cellular ageing of human diploid fibroblasts

    PubMed Central

    2013-01-01

    Background Human diploid fibroblasts (HDFs) undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular ageing. Even though beneficial effects of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction (TRF) have been reported, ongoing studies in relation to ageing is of interest to determine possible protective effects that may reverse the effect of ageing. The aim of this study was to evaluate the effect of P. betle, C. vulgaris and TRF in preventing cellular ageing of HDFs by determining the activity of antioxidant enzymes viz.; catalase, superoxide dismutase (SOD) and glutathione peroxidase. Methods Different passages of HDFs were treated with P. betle, C. vulgaris and TRF for 24 h prior to enzymes activity determination. Senescence-associated beta-galactosidase (SA β-gal) expression was assayed to validate cellular ageing. Results In cellular ageing of HDFs, catalase and glutathione peroxidase activities were reduced, but SOD activity was heightened during pre-senescence. P. betle exhibited the strongest antioxidant activity by reducing SA β-gal expression, catalase activities in all age groups, and SOD activity. TRF exhibited a strong antioxidant activity by reducing SA β-gal expression, and SOD activity in senescent HDFs. C. vulgaris extract managed to reduce SOD activity in senescent HDFs. Conclusion P. betle, C. vulgaris, and TRF have the potential as anti-ageing entities which compensated the role of antioxidant enzymes in cellular ageing of HDFs. PMID:23948056

  7. Comparative effect of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction on antioxidant enzymes activity in cellular ageing of human diploid fibroblasts.

    PubMed

    Makpol, Suzana; Yeoh, Thong Wei; Ruslam, Farah Adilah Che; Arifin, Khaizurin Tajul; Yusof, Yasmin Anum Mohd

    2013-08-16

    Human diploid fibroblasts (HDFs) undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular ageing. Even though beneficial effects of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction (TRF) have been reported, ongoing studies in relation to ageing is of interest to determine possible protective effects that may reverse the effect of ageing. The aim of this study was to evaluate the effect of P. betle, C. vulgaris and TRF in preventing cellular ageing of HDFs by determining the activity of antioxidant enzymes viz.; catalase, superoxide dismutase (SOD) and glutathione peroxidase. Different passages of HDFs were treated with P. betle, C. vulgaris and TRF for 24 h prior to enzymes activity determination. Senescence-associated beta-galactosidase (SA β-gal) expression was assayed to validate cellular ageing. In cellular ageing of HDFs, catalase and glutathione peroxidase activities were reduced, but SOD activity was heightened during pre-senescence. P. betle exhibited the strongest antioxidant activity by reducing SA β-gal expression, catalase activities in all age groups, and SOD activity. TRF exhibited a strong antioxidant activity by reducing SA β-gal expression, and SOD activity in senescent HDFs. C. vulgaris extract managed to reduce SOD activity in senescent HDFs. P. betle, C. vulgaris, and TRF have the potential as anti-ageing entities which compensated the role of antioxidant enzymes in cellular ageing of HDFs.

  8. Modeling the effect of microscopic driving behaviors on Kerner's time-delayed traffic breakdown at traffic signal using cellular automata

    NASA Astrophysics Data System (ADS)

    Wang, Yang; Chen, Yan-Yan

    2016-12-01

    The signalized traffic is considerably complex due to the fact that various driving behaviors have emerged to respond to traffic signals. However, the existing cellular automaton models take the signal-vehicle interactions into account inadequately, resulting in a potential risk that vehicular traffic flow dynamics may not be completely explored. To remedy this defect, this paper proposes a more realistic cellular automaton model by incorporating a number of the driving behaviors typically observed when the vehicles are approaching a traffic light. In particular, the anticipatory behavior proposed in this paper is realized with a perception factor designed by considering the vehicle speed implicitly and the gap to its preceding vehicle explicitly. Numerical simulations have been performed based on a signal controlled road which is partitioned into three sections according to the different reactions of drivers. The effects of microscopic driving behaviors on Kerner's time-delayed traffic breakdown at signal (Kerner 2011, 2013) have been investigated with the assistance of spatiotemporal pattern and trajectory analysis. Furthermore, the contributions of the driving behaviors on the traffic breakdown have been statistically examined. Finally, with the activation of the anticipatory behavior, the influences of the other driving behaviors on the formation of platoon have been investigated in terms of the number of platoons, the averaged platoon size, and the averaged flow rate.

  9. Effect of solid distribution on elastic properties of open-cell cellular solids using numerical and experimental methods.

    PubMed

    Zargarian, A; Esfahanian, M; Kadkhodapour, J; Ziaei-Rad, S

    2014-09-01

    Effect of solid distribution between edges and vertices of three-dimensional cellular solid with an open-cell structure was investigated both numerically and experimentally. Finite element analysis (FEA) with continuum elements and appropriate periodic boundary condition was employed to calculate the elastic properties of cellular solids using tetrakaidecahedral (Kelvin) unit cell. Relative densities between 0.01 and 0.1 and various values of solid fractions were considered. In order to validate the numerical model, three scaffolds with the relative density of 0.08, but different amounts of solid in vertices, were fabricated via 3-D printing technique. Good agreement was observed between numerical simulation and experimental results. Results of numerical simulation showed that, at low relative densities (<0.03), Young׳s modulus increased by shifting materials away from edges to vertices at first and then decreased after reaching a critical point. However, for the high values of relative density, Young׳s modulus increased monotonically. Mechanisms of such a behavior were discussed in detail. Results also indicated that Poisson׳s ratio decreased by increasing relative density and solid fraction in vertices. By fitting a curve to the data obtained from the numerical simulation and considering the relative density and solid fraction in vertices, empirical relations were derived for Young׳s modulus and Poisson׳s ratio. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Effect of culture age on 1,3-dinitrobenzene metabolism and indicators of cellular toxicity in rat testicular cells.

    PubMed

    Brown, C D; Miller, M G

    1991-01-01

    The metabolism and toxicity of 1,3-dinitrobenzene(1,3-DNB) were examined in rat testicular cells that had been cultured for various amounts of time. The three cell systems utilized were: freshly isolated suspensions of Sertoli/germ cells; the same Sertoli/germ cells co-cultured for 24 hr; and Sertoli cell-enriched monolayers derived from the co-cultures and cultured for 96 hr. Indicators of toxicity were MTT reduction, neutral red incorporation, cellular ATP levels and lactate secretion into the media. 1,3-DNB (5-50 mum) caused a significant concentration-dependent decline in cellular ATP levels in the fresh cell suspension, but not in the cells that had been cultured for longer. No changes were observed either in MTT reduction or neutral red incorporation. Increased secretion of lactate into the media also did not prove to be a sensitive indicator of toxicity. Interestingly, 1,3-DNB metabolism to nitroaniline, nitroacetanilide and a covalently bound species was two to three times greater in the fresh cells, compared with either the 24- or 96-hr cell cultures. The data indicate that time in culture may have significant effects on both the capacity of testicular cells to metabolize 1,3-DNB and susceptibility to toxicity.

  11. Comparing the effects of nano-sized sugarcane fiber with cellulose and psyllium on hepatic cellular signaling in mice

    PubMed Central

    Wang, Zhong Q; Yu, Yongmei; Zhang, Xian H; Floyd, Z Elizabeth; Boudreau, Anik; Lian, Kun; Cefalu, William T

    2012-01-01

    Aim To compare the effects of dietary fibers on hepatic cellular signaling in mice. Methods Mice were randomly divided into four groups (n = 9/group): high-fat diet (HFD) control, cellulose, psyllium, and sugarcane fiber (SCF) groups. All mice were fed a HFD with or without 10% dietary fiber (w/w) for 12 weeks. Body weight, food intake, fasting glucose, and fasting insulin levels were measured. At the end of the study, hepatic fibroblast growth factor (FGF) 21, AMP-activated protein kinase (AMPK) and insulin signaling protein content were determined. Results Hepatic FGF21 content was significantly lowered, but βKlotho, fibroblast growth factor receptor 1, fibroblast growth factor receptor 3, and peroxisome proliferator-activated receptor alpha proteins were significantly increased in the SCF group compared with those in the HFD group (P < 0.01). SCF supplementation also significantly enhanced insulin and AMPK signaling, as well as decreased hepatic triglyceride and cholesterol in comparison with the HFD mice. The study has shown that dietary fiber, especially SCF, significantly attenuates lipid accumulation in the liver by enhancing hepatic FGF21, insulin, and AMPK signaling in mice fed a HFD. Conclusion This study suggests that the modulation of gastrointestinal factors by dietary fibers may play a key role in both enhancing hepatic multiple cellular signaling and reducing lipid accumulation. PMID:22787396

  12. The effects of chemotherapeutics on cellular metabolism and consequent immune recognition.

    PubMed

    Newell, M Karen; Melamede, Robert; Villalobos-Menuey, Elizabeth; Swartzendruber, Douglas; Trauger, Richard; Camley, Robert E; Crisp, William

    2004-02-02

    Awidely held view is that oncolytic agents induce death of tumor cells directly. In this report we review and discuss the apoptosis-inducing effects of chemotherapeutics, the effects of chemotherapeutics on metabolic function, and the consequent effects of metabolic function on immune recognition. Finally, we propose that effective chemotherapeutic and/or apoptosis-inducing agents, at concentrations that can be achieved physiologically, do not kill tumor cells directly. Rather, we suggest that effective oncolytic agents sensitize immunologically altered tumor cells to immune recognition and immune-directed cell death.

  13. The effects of chemotherapeutics on cellular metabolism and consequent immune recognition

    PubMed Central

    Newell, M Karen; Melamede, Robert; Villalobos-Menuey, Elizabeth; Swartzendruber, Douglas; Trauger, Richard; Camley, Robert E; Crisp, William

    2004-01-01

    A widely held view is that oncolytic agents induce death of tumor cells directly. In this report we review and discuss the apoptosis-inducing effects of chemotherapeutics, the effects of chemotherapeutics on metabolic function, and the consequent effects of metabolic function on immune recognition. Finally, we propose that effective chemotherapeutic and/or apoptosis-inducing agents, at concentrations that can be achieved physiologically, do not kill tumor cells directly. Rather, we suggest that effective oncolytic agents sensitize immunologically altered tumor cells to immune recognition and immune-directed cell death. PMID:14756899

  14. Earthquake Early Warning: User Education and Designing Effective Messages

    NASA Astrophysics Data System (ADS)

    Burkett, E. R.; Sellnow, D. D.; Jones, L.; Sellnow, T. L.

    2014-12-01

    The U.S. Geological Survey (USGS) and partners are transitioning from test-user trials of a demonstration earthquake early warning system (ShakeAlert) to deciding and preparing how to implement the release of earthquake early warning information, alert messages, and products to the public and other stakeholders. An earthquake early warning system uses seismic station networks to rapidly gather information about an occurring earthquake and send notifications to user devices ahead of the arrival of potentially damaging ground shaking at their locations. Earthquake early warning alerts can thereby allow time for actions to protect lives and property before arrival of damaging shaking, if users are properly educated on how to use and react to such notifications. A collaboration team of risk communications researchers and earth scientists is researching the effectiveness of a chosen subset of potential earthquake early warning interface designs and messages, which could be displayed on a device such as a smartphone. Preliminary results indicate, for instance, that users prefer alerts that include 1) a map to relate their location to the earthquake and 2) instructions for what to do in response to the expected level of shaking. A number of important factors must be considered to design a message that will promote appropriate self-protective behavior. While users prefer to see a map, how much information can be processed in limited time? Are graphical representations of wavefronts helpful or confusing? The most important factor to promote a helpful response is the predicted earthquake intensity, or how strong the expected shaking will be at the user's location. Unlike Japanese users of early warning, few Californians are familiar with the earthquake intensity scale, so we are exploring how differentiating instructions between intensity levels (e.g., "Be aware" for lower shaking levels and "Drop, cover, hold on" at high levels) can be paired with self-directed supplemental

  15. Acetaldehyde involvement in ethanol's postabsortive effects during early ontogeny.

    PubMed

    March, Samanta M; Abate, P; Molina, Juan C

    2013-01-01

    Clinical and biomedical studies sustains the notion that early ontogeny is a vulnerable window to the impact of alcohol. Experiences with the drug during these stages increase latter disposition to prefer, use or abuse ethanol. This period of enhanced sensitivity to ethanol is accompanied by a high rate of activity in the central catalase system, which metabolizes ethanol in the brain. Acetaldehyde (ACD), the first oxidation product of ethanol, has been found to share many neurobehavioral effects with the drug. Cumulative evidence supports this notion in models employing adults. Nevertheless very few studies have been conducted to analyze the role of ACD in ethanol postabsorptive effects, in newborns or infant rats. In this work we review recent experimental literature that syndicates ACD as a mediator agent of reinforcing aspects of ethanol, during early ontogenetic stages. We also show a meta-analytical correlational approach that proposes how differences in the activity of brain catalase across ontogeny, could be modulating patterns of ethanol consumption.

  16. Interleukin-7 in Patients With Chronic Hepatitis B May Have Effect on T Follicular Helper Cells and Specific Cellular Immunity.

    PubMed

    Zhong, Hua; Xibing, Gu; Yaping, Dai; Zheng, Wang; Decai, Fu; Xiaoye, Guo; Hangyuan, Wu; Dong, Wang; Zhonghua, Lu

    2016-09-01

    In patients with chronic hepatitis B (CHB), the relation of interkeukin-7 (IL-7) to either the T follicular helper cells (Tfh cells) or to a specific cellular immune response is not clear. The present study aims to explore the possible relationship of IL-7 to Tfh cells and to hepatitis B virus (HBV)-specific cellular immune response in patients with CHB. Ninety-one adult patients with CHB were divided into groups A, B, and C, according to the patients' IL-7 levels (low, medium, and high). Tfh cells and HBV-specific cytotoxic T lymphocytes (CTLs) were detected with flow cytometry; IL-7 and IL-21 were determined with a double antibody sandwich enzyme-linked immunosorbent assay; and HBV DNA was determined by using a real-time fluorescent quantitative polymerase chain reaction. The results showed that the levels of IL-7, Tfh cells, IL-21, and HBV-specific CTLs of patients in group C were significantly higher than those of patients in group B, (P < 0.01 for each comparison) and that the levels of these four parameters of patients in group B were significantly higher than those of the patients in group A (P < 0.01 for each comparison). Meanwhile, the level of HBV DNA of the patients in group C was significantly lower than that of the patients in group B (P < 0.01), and that of the patients in group B was significantly lower than that of the patients in group A (P < 0.05). Multiple linear regression analyses showed that IL-7, Tfh cells, IL-21, and HBV-specific CTL might have effects on HBV DNA and that only the HBV-specific CTL had an independent effect on HBV DNA (P < 0.01). IL-7, Tfh cells, and IL-21 showed independent effects on HBV-specific CTL (P < 0.05, P < 0.01, and P < 0.01). This study suggests that the IL-7 level of CHB patients may be related to Tfh cells. In CHB patients, IL-7 possibly increases the level of Tfh cells and HBV-specific cellular immune responses and thereby reduces the HBV DNA level.

  17. Comparing the effects of mitochondrial targeted and localized antioxidants with cellular antioxidants in human skin cells exposed to UVA and hydrogen peroxide.

    PubMed

    Oyewole, Anne O; Wilmot, Marie-Claire; Fowler, Mark; Birch-Machin, Mark A

    2014-01-01

    Skin cancer and aging are linked to increased cellular reactive oxygen species (ROS), particularly following exposure to ultraviolet A (UVA) in sunlight. As mitochondria are the main source of cellular ROS, this study compared the protective effects of mitochondria-targeted and -localized antioxidants (MitoQ and tiron, respectively) with cellular antioxidants against oxidative stress-induced [UVA and hydrogen peroxide (H2O2)] mitochondrial DNA (mtDNA) damage in human dermal fibroblasts. With the use of a long quantitative PCR assay, tiron (EC50 10 mM) was found to confer complete (100%) protection (P<0.001) against both UVA- and H2O2-induced mtDNA damage, whereas MitoQ (EC50 750 nM) provided less protection (17 and 32%, respectively; P<0.05). This particular protective effect of tiron was greater than a range of cellular antioxidants investigated. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway provides cellular protection against oxidative stress. An ELISA assay for the Nrf2 target gene heme oxygenase-1 (HO-1) and studies using Nrf2 small interfering RNA both indicated that tiron's mode of action was Nrf2 independent. The comet assay showed that tiron's protective effect against H2O2-induced nuclear DNA damage was greater than the cellular antioxidants and MitoQ (P<0.001). This study provides a platform to investigate molecules with similar structure to tiron as potent and clinically relevant antioxidants.

  18. Distinct Effects of Rotenone, 1-methyl-4-phenylpyridinium and 6-hydroxydopamine on Cellular Bioenergetics and Cell Death

    PubMed Central

    Giordano, Samantha; Lee, Jisun; Darley-Usmar, Victor M.; Zhang, Jianhua

    2012-01-01

    Parkinson’s disease is characterized by dopaminergic neurodegeneration and is associated with mitochondrial dysfunction. The bioenergetic susceptibility of dopaminergic neurons to toxins which induce Parkinson’s like syndromes in animal models is then of particular interest. For example, rotenone, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+), and 6-hydroxydopamine (6-OHDA), have been shown to induce dopaminergic cell death in vivo and in vitro. Exposure of animals to these compounds induce a range of responses characteristics of Parkinson’s disease, including dopaminergic cell death, and Reactive Oxygen Species (ROS) production. Here we test the hypothesis that cellular bioenergetic dysfunction caused by these compounds correlates with induction of cell death in differentiated dopaminergic neuroblastoma SH-SY5Y cells. At increasing doses, rotenone induced significant cell death accompanied with caspase 3 activation. At these concentrations, rotenone had an immediate inhibition of mitochondrial basal oxygen consumption rate (OCR) concomitant with a decrease of ATP-linked OCR and reserve capacity, as well as a stimulation of glycolysis. MPP+ exhibited a different behavior with less pronounced cell death at doses that nearly eliminated basal and ATP-linked OCR. Interestingly, MPP+, unlike rotenone, stimulated bioenergetic reserve capacity. The effects of 6-OHDA on bioenergetic function was markedly less than the effects of rotenone or MPP+ at cytotoxic doses, suggesting a mechanism largely independent of bioenergetic dysfunction. These studies suggest that these dopaminergic neurotoxins induce cell death through distinct mechanisms and differential effects on cellular bioenergetics. PMID:22970265

  19. Effects of early life stress on amygdala and striatal development

    PubMed Central

    Fareri, Dominic S.; Tottenham, Nim

    2016-01-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one’s social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. PMID:27174149

  20. Effects of early life stress on amygdala and striatal development.

    PubMed

    Fareri, Dominic S; Tottenham, Nim

    2016-06-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one's social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. A probabilistic cellular automata model for the dynamics of a population driven by logistic growth and weak Allee effect

    NASA Astrophysics Data System (ADS)

    Mendonça, J. R. G.

    2018-04-01

    We propose and investigate a one-parameter probabilistic mixture of one-dimensional elementary cellular automata under the guise of a model for the dynamics of a single-species unstructured population with nonoverlapping generations in which individuals have smaller probability of reproducing and surviving in a crowded neighbourhood but also suffer from isolation and dispersal. Remarkably, the first-order mean field approximation to the dynamics of the model yields a cubic map containing terms representing both logistic and weak Allee effects. The model has a single absorbing state devoid of individuals, but depending on the reproduction and survival probabilities can achieve a stable population. We determine the critical probability separating these two phases and find that the phase transition between them is in the directed percolation universality class of critical behaviour.

  2. [Dose rate-dependent cellular and molecular effects of ionizing radiation].

    PubMed

    Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

    2008-09-11

    The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

  3. Endocrine, teratogenic and neurotoxic effects of cyanobacteria detected by cellular in vitro and zebrafish embryos assays.

    PubMed

    Jonas, Adam; Scholz, Stefan; Fetter, Eva; Sychrova, Eliska; Novakova, Katerina; Ortmann, Julia; Benisek, Martin; Adamovsky, Ondrej; Giesy, John P; Hilscherova, Klara

    2015-02-01

    Cyanobacteria contain various types of bioactive compounds, which could cause adverse effects on organisms. They are released into surface waters during cyanobacterial blooms, but there is little information on their potential relevance for effects in vivo. In this study presence of bioactive compounds was characterized in cyanobacteria Microcystis aeruginosa (Chroococcales), Planktothrix agardhii (Oscillatoriales) and Aphanizomenon gracile (Nostocales) with selected in vitro assays. The in vivo relevance of detected bioactivities was analysed using transgenic zebrafish embryos tg(cyp19a1b-GFP). Teratogenic potency was assessed by analysis of developmental disorders and effects on functions of the neuromuscular system by video tracking of locomotion. Estrogenicity in vitro corresponded to 0.95-54.6 ng estradiol equivalent(g dry weight (dw))(-1). In zebrafish embryos, estrogenic effects could not be detected potentially because they were masked by high toxicity. There was no detectable (anti)androgenic/glucocorticoid activity in any sample. Retinoid-like activity was determined at 1-1.3 μg all-trans-retinoic acid equivalent(g dw)(-1). Corresponding to the retinoid-like activity A. gracile extract also caused teratogenic effects in zebrafish embryos. Furthermore, exposure to biomass extracts at 0.3 gd wL(-1) caused increase of body length in embryos. There were minor effects on locomotion caused by 0.3 gd wL(-1)M. aeruginosa and P. agardhii extracts. The traditionally measured cyanotoxins microcystins did not seem to play significant role in observed effects. This indicates importance of other cyanobacterial compounds at least towards some species or their developmental phases. More attention should be paid to activity of retinoids, estrogens and other bioactive substances in phytoplankton using in vitro and in vivo bioassays. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Effect of the nanoformulation of siRNA-lipid assemblies on their cellular uptake and immune stimulation

    PubMed Central

    Kubota, Kohei; Onishi, Kohei; Sawaki, Kazuaki; Li, Tianshu; Mitsuoka, Kaoru; Sato, Takaaki; Takeoka, Shinji

    2017-01-01

    Two lipid-based nanoformulations have been used to date in clinical studies: lipoplexes and lipid nanoparticles (LNPs). In this study, we prepared small interfering RNA (siRNA)-loaded carriers using lipid components of the same composition to form molecular assemblies of differing structures, and evaluated the impact of structure on cellular uptake and immune stimulation. Lipoplexes are electrostatic complexes formed by mixing preformed cationic lipid liposomes with anionic siRNA in an aqueous environment, whereas LNPs are nanoparticles embedding siRNA prepared by mixing an alcoholic lipid solution with an aqueous siRNA solution in one step. Although the physicochemical properties of lipoplexes and LNPs were similar except for small increases in apparent size of lipoplexes and zeta potential of LNPs, siRNA uptake efficiency of LNPs was significantly higher than that of lipoplexes. Furthermore, in the case of LNPs, both siRNA and lipid were effectively incorporated into cells in a co-assembled state; however, in the case of lipoplexes, the amount of siRNA internalized into cells was small in comparison with lipid. siRNAs in lipoplexes were thought to be more likely to localize on the particle surface and thereby undergo dissociation into the medium. Inflammatory cytokine responses also appeared to differ between lipoplexes and LNPs. For tumor necrosis factor-α, release was mainly caused by siRNA. On the other hand, the release of interleukin-1β was mainly due to the cationic nature of particles. LNPs released lower amounts of tumor necrosis factor-α and interleukin-1β than lipoplexes and were thus considered to be better tolerated with respect to cytokine release. In conclusion, siRNA-loaded nanoformulations effect their cellular uptake and immune stimulation in a manner that depends on the structure of the molecular assembly; therefore, nanoformulations should be optimized before extending studies into the in vivo environment. PMID:28790820

  5. Effects of cell culture media on the dynamic formation of protein-nanoparticle complexes and influence on the cellular response.

    PubMed

    Maiorano, Gabriele; Sabella, Stefania; Sorce, Barbara; Brunetti, Virgilio; Malvindi, Maria Ada; Cingolani, Roberto; Pompa, Pier Paolo

    2010-12-28

    The development of appropriate in vitro protocols to assess the potential toxicity of the ever expanding range of nanoparticles represents a challenging issue, because of the rapid changes of their intrinsic physicochemical properties (size, shape, reactivity, surface area, etc.) upon dispersion in biological fluids. Dynamic formation of protein coating around nanoparticles is a key molecular event, which may strongly impact the biological response in nanotoxicological tests. In this work, by using citrate-capped gold nanoparticles (AuNPs) of different sizes as a model, we show, by several spectroscopic techniques (dynamic light scattering, UV-visible, plasmon resonance light scattering), that proteins-NP interactions are differently mediated by two widely used cellular media (i.e., Dulbecco Modified Eagle's medium (DMEM) and Roswell Park Memorial Institute medium (RPMI), supplemented with fetal bovine serum). We found that, while DMEM elicits the formation of a large time-dependent protein corona, RPMI shows different dynamics with reduced protein coating. Characterization of these nanobioentities was also performed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and mass spectroscopy, revealing that the average composition of protein corona does not reflect the relative abundance of serum proteins. To evaluate the biological impact of such hybrid bionanostructures, several comparative viability assays onto two cell lines (HeLa and U937) were carried out in the two media, in the presence of 15 nm AuNPs. We observed that proteins/NP complexes formed in RPMI are more abundantly internalized in cells as compared to DMEM, overall exerting higher cytotoxic effects. These results show that, beyond an in-depth NPs characterization before cellular experiments, a detailed understanding of the effects elicited by cell culture media on NPs is crucial for standardized nanotoxicology tests.

  6. Cell viability studies and operation in cellular culture medium of n-type organic field-effect transistors

    NASA Astrophysics Data System (ADS)

    Barra, M.; Viggiano, D.; Di Capua, R.; Di Girolamo, F.; Santoro, F.; Taglialatela, M.; Cassinese, A.

    2012-02-01

    The possibility of the fabrication of organic devices suitable to be applied in bio-sensing fields depends largely on the availability of organic compounds displaying robust electrical properties even in aqueous solutions and effective biocompatibility features. In this paper, we report about the good cellular biocompatibility and the electrical response stability in an ionic medium of n-type organic transistors based on the recently developed PDI-8CN2 oligomer. The biocompatibility has been tested by analyzing the adhesion and viability of two different cell lines, human epithelial HeLa cells and murine neuronal F11 cells, on PDI-8CN2 films grown by organic molecular beam deposition (OMBD) on SiO2 substrates. The effect of film thickness on cell attachment was also tested. Uncoated SiO2 substrates were used as control surfaces and sexithiophene (T6) as device testing control. Moreover, the possible toxicity of -CN groups of PDI-8CN2 was tested on HeLa cell cultures, using PDI-8 and T6 molecules as controls. Results showed that, although at high concentration these organic compounds are toxic in solution, if they are presented in form of film, cell lines can attach and grow on them. The electrical response stability of PDI-8CN2 transistors in a cellular culture medium characterized by high concentrations of ionic species has been also investigated. For this purpose, low-voltage operation devices with VGS ranging from -5 V to 5 V, able to strongly reduce the influence of Faradaic currents coming from the electrical operation in an highly ionic environment, have been fabricated on 35 nm thick SiO2 layers and electrically characterized. These results are useful to experimentally define the main critical issues to be further addressed for the fabrication of reliable bio-sensors based on organic transistors.

  7. The effect of glucagon-like peptide-1 in the management of diabetes mellitus: cellular and molecular mechanisms.

    PubMed

    Lotfy, Mohamed; Singh, Jaipaul; Rashed, Hameed; Tariq, Saeed; Zilahi, Erika; Adeghate, Ernest

    2014-11-01

    Incretins, such as glucagon-like peptide-1 (GLP)-1, have been shown to elevate plasma insulin concentration. The purpose of this study is to investigate the cellular and molecular basis of the beneficial effects of GLP-1. Normal and diabetic male Wistar rats were treated with GLP-1 (50 ng/kg body weight) for 10 weeks. At the end of the experiment, pancreatic tissues were taken for immunohistochemistry, immunoelectron microscopy and real-time polymerase chain reaction studies. Samples of blood were retrieved from the animals for the measurement of enzymes and insulin. The results show that treatment of diabetic rats with GLP-1 caused significant (P < 0.05) reduction in body weight gain and blood glucose level. GLP-1 (10(-12)-10(-6) M) induced significant (P < 0.01) dose-dependent increases in insulin release from the pancreas of normal and diabetic rats compared to basal. Diabetes-induced abnormal liver (aspartate aminotransferase and alanine aminotransferase) and kidney (blood urea nitrogen and uric acid) parameters were corrected in GLP-1-treated rats compared to controls. GLP-1 treatment induced significant (P < 0.05) elevation in the expression of pancreatic duodenal homeobox-1, heat shock protein-70, glutathione peroxidase, insulin receptor and GLP-1-receptor genes in diabetic animals compared to controls. GLP-1 is present in pancreatic beta cells and significantly (P < 0.05) increased the number of insulin-, glutathione reductase- and catalase-immunoreactive islet cells. The results of this study show that GLP-1 is co-localized with insulin and seems to exert its beneficial effects by increasing cellular concentrations of endogenous antioxidant genes and other genes involved in the maintenance of pancreatic beta cell structure and function.

  8. Effect of the nanoformulation of siRNA-lipid assemblies on their cellular uptake and immune stimulation.

    PubMed

    Kubota, Kohei; Onishi, Kohei; Sawaki, Kazuaki; Li, Tianshu; Mitsuoka, Kaoru; Sato, Takaaki; Takeoka, Shinji

    2017-01-01

    Two lipid-based nanoformulations have been used to date in clinical studies: lipoplexes and lipid nanoparticles (LNPs). In this study, we prepared small interfering RNA (siRNA)-loaded carriers using lipid components of the same composition to form molecular assemblies of differing structures, and evaluated the impact of structure on cellular uptake and immune stimulation. Lipoplexes are electrostatic complexes formed by mixing preformed cationic lipid liposomes with anionic siRNA in an aqueous environment, whereas LNPs are nanoparticles embedding siRNA prepared by mixing an alcoholic lipid solution with an aqueous siRNA solution in one step. Although the physicochemical properties of lipoplexes and LNPs were similar except for small increases in apparent size of lipoplexes and zeta potential of LNPs, siRNA uptake efficiency of LNPs was significantly higher than that of lipoplexes. Furthermore, in the case of LNPs, both siRNA and lipid were effectively incorporated into cells in a co-assembled state; however, in the case of lipoplexes, the amount of siRNA internalized into cells was small in comparison with lipid. siRNAs in lipoplexes were thought to be more likely to localize on the particle surface and thereby undergo dissociation into the medium. Inflammatory cytokine responses also appeared to differ between lipoplexes and LNPs. For tumor necrosis factor-α, release was mainly caused by siRNA. On the other hand, the release of interleukin-1β was mainly due to the cationic nature of particles. LNPs released lower amounts of tumor necrosis factor-α and interleukin-1β than lipoplexes and were thus considered to be better tolerated with respect to cytokine release. In conclusion, siRNA-loaded nanoformulations effect their cellular uptake and immune stimulation in a manner that depends on the structure of the molecular assembly; therefore, nanoformulations should be optimized before extending studies into the in vivo environment.

  9. Effect of compound glycyrrhizin injection on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment.

    PubMed

    Cao, Zong-xin; Zhao, Zhong-fang; Zhao, Xiu-fen

    2006-12-01

    To investigate the effects of Compound Glycyrrhizin Injection (CGI) on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment (IM-LI) and to explore its clinical therapeutic effect. Forty-two patients with IM-LI were randomly assigned, according to the randomizing number table, to two groups, 20 in the control group and 22 in the treated group. All the patients were treated with conventional treatment, but to those in the treated group, CGI was given additionally once a day, at the dosage of 10 ml for children aged below 2 years, 20 ml for 2-4 years old, 30 ml for 5-7 years old and 40 ml for 8- 12 years old, in 100-200 ml of 5% glucose solution by intravenous dripping. The treatment lasted for 2 weeks. T lymphocyte subsets and serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) were detected before and after treatment. Besides, a normal control group consisting of 20 healthy children was also set up. Baseline of the percentage of CD3 + , CD8 + lymphocyte and serum levels of ALT, AST, TBiL in the children with IM-LI were markedly higher, while the percentage of CD4 + lymphocyte and the CD4 + /CD8 + ratio was markedly lower in IM-LI children as compared with the corresponding indices in the healthy children ( P<0.01). These indices were improved after treatment in both groups of patients, but the improvement in the treated group was better than that in the control group (P<0.01). Cellular immunity dysfunction often occurs in patients with IM-LI, and CGI treatment can not only obviously promote the recovery of liver function, but also regulate the immune function in organism.

  10. Augmented cellular uptake of nanoparticles using tea catechins: effect of surface modification on nanoparticle-cell interaction

    NASA Astrophysics Data System (ADS)

    Lu, Yi-Ching; Luo, Pei-Chun; Huang, Chun-Wan; Leu, Yann-Lii; Wang, Tzu-Hao; Wei, Kuo-Chen; Wang, Hsin-Ell; Ma, Yunn-Hwa

    2014-08-01

    Nanoparticles may serve as carriers in targeted therapeutics; interaction of the nanoparticles with a biological system may determine their targeting effects and therapeutic efficacy. Epigallocatechin-3-gallate (EGCG), a major component of tea catechins, has been conjugated with nanoparticles and tested as an anticancer agent. We investigated whether EGCG may enhance nanoparticle uptake by tumor cells. Cellular uptake of a dextran-coated magnetic nanoparticle (MNP) was determined by confocal microscopy, flow cytometry or a potassium thiocyanate colorimetric method. We demonstrated that EGCG greatly enhanced interaction and/or internalization of MNPs (with or without polyethylene glycol) by glioma cells, but not vascular endothelial cells. The enhancing effects are both time- and concentration-dependent. Such effects may be induced by a simple mix of MNPs with EGCG at a concentration as low as 1-3 μM, which increased MNP uptake 2- to 7-fold. In addition, application of magnetic force further potentiated MNP uptake, suggesting a synergetic effect of EGCG and magnetic force. Because the effects of EGCG were preserved at 4 °C, but not when EGCG was removed from the culture medium prior to addition of MNPs, a direct interaction of EGCG and MNPs was implicated. Use of an MNP-EGCG composite produced by adsorption of EGCG and magnetic separation also led to an enhanced uptake. The results reveal a novel interaction of a food component and nanocarrier system, which may be potentially amenable to magnetofection, cell labeling/tracing, and targeted therapeutics.

  11. Cellular and laminar expression of Dab-1 during the postnatal critical period in cat visual cortex and the effects of dark rearing.

    PubMed

    Kiser, Paul J; Liu, Zijing; Wilt, Steven D; Mower, George D

    2011-04-06

    This study describes postnatal critical period changes in cellular and laminar expression of Dab-1, a gene shown to play a role in controlling neuronal positioning during embryonic brain development, in cat visual cortex and the effects of dark rearing (DR). At 1week, there is dense cellular staining which is uniform across cortical layers and very light neuropil staining. At the peak of the critical period (5weeks), dense cell staining is largely restricted to large pyramidal cells of deep layer III and layer V, there is faint cell body staining throughout all cortical layers, neuropil staining is markedly increased and uniform in layers III to VI. This dramatic change in laminar and cellular labeling is independent of visual input, since immunostaining is similar in 5-week DR cats. By 10weeks, the mature laminar and cellular staining pattern is established and the major subsequent change is a further reduction in the density of cellular staining in all cortical layers. Neuropil staining is pronounced and uniform across cortical layers. These developmental changes are altered by DR. Quantification by cell counts indicated that age and DR interact such that differences in cellular expression are opposite in direction between 5- and 20-week-old cats. This bidirectional regulation of cellular expression is the same in all cortical laminae. The bidirectional regulation of cellular expression matches the effects of age and DR on physiological plasticity during the critical period as assessed by ocular dominance shifts in response to monocular deprivation. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. [Effects of electromagnetic fields emitted by cellular phone on auditory and vestibular labyrinth].

    PubMed

    Sievert, U; Eggert, S; Goltz, S; Pau, H W

    2007-04-01

    It is the subject of this study to investigate the biological effect of the HF radiation produced by the Global System for Mobile Communications-( GSM)-mobile phone on the inner ear with its sensors of the vestibular and auditive systems. Thermographic investigations made on various model materials and on the human temporal bone should show whether mobile phone does induce any increases of temperature which would lead to a relevant stimulus for the auditive and vestibular system or not. We carried out video-nystagmographic recordings of 13 subjects, brainstem electric response audiometry of 24 ears, and recordings of distorsion products of otoacoustic emissions of 20 ears. All tests were made with and without a mobile phone in use. The data was then analyzed for variation patterns in the functional parameters of the hearing and balance system that are subject to the (non)existence of electromagnetic radiation from the mobile phone. The thermographic investigations suggest that the mobile phone does not induce any increases of temperature which would lead to a relevant stimulus for the auditive and vestibular system. Video-nystagmographic recordings under field effect do not furnish any indication of vestibular reactions generated by field effects. Compared with the recording without field, the brainstem electric response audiometry under field effect did not reveal any changes of the parameters investigated, i. e. absolute latency of the peaks I, III, V and the interpeak latency between the peaks I and V. The distorsion products of otoacoustic emissions do not indicate, comparing the three measuring situations, i. e. before field effect, pulsed field and continuous field, any possible impacts of the HF field on the spectrum or levels of emissions for none of the probands. The investigations made show that the electromagnetic fields generated in using the mobile phone do not have an effect on the inner ear and auditive system to the colliculus inferior in the

  13. At the interface of antioxidant signalling and cellular function: Key polyphenol effects

    PubMed Central

    Kerimi, Asimina

    2016-01-01

    The hypothesis that dietary (poly)phenols promote well‐being by improving chronic disease‐risk biomarkers, such as endothelial dysfunction, chronic inflammation and plasma uric acid, is the subject of intense current research, involving human interventions studies, animal models and in vitro mechanistic work. The original claim that benefits were due to the direct antioxidant properties of (poly)phenols has been mostly superseded by detailed mechanistic studies on specific molecular targets. Nevertheless, many proposed mechanisms in vivo and in vitro are due to modulation of oxidative processes, often involving binding to specific proteins and effects on cell signalling. We review the molecular mechanisms for 3 actions of (poly)phenols on oxidative processes where there is evidence in vivo from human intervention or animal studies. (1) Effects of (poly) phenols on pathways of chronic inflammation leading to prevention of some of the damaging effects associated with the metabolic syndrome. (2) Interaction of (poly)phenols with endothelial cells and smooth muscle cells, leading to effects on blood pressure and endothelial dysfunction, and consequent reduction in cardiovascular disease risk. (3) The inhibition of xanthine oxidoreductase leading to modulation of intracellular superoxide and plasma uric acid, a risk factor for developing type 2 diabetes. PMID:26887821

  14. Low-temperature plasma-induced antiproliferative effects on multi-cellular tumor spheroids

    NASA Astrophysics Data System (ADS)

    Plewa, Joseph-Marie; Yousfi, Mohammed; Frongia, Céline; Eichwald, Olivier; Ducommun, Bernard; Merbahi, Nofel; Lobjois, Valérie

    2014-04-01

    Biomedical applications of low-temperature plasmas are of growing interest, especially in the field of plasma-induced anti-tumor effects. The present work is aimed at investigating the regionalized antiproliferative effects of low-temperature plasmas on a multicellular tumor spheroid (MCTS), a model that mimics the 3D organization and regionalization of a microtumor region. We report that a low-temperature plasma jet, using helium flow in open air, inhibits HCT116 colon carcinoma MCTS growth in a dose-dependent manner. This growth inhibition is associated with the loss of Ki67, and the regionalized accumulation of DNA damage detected by histone H2AX phosphorylation. This regionalized genotoxic effect leads to massive cell death and loss of the MCTS proliferative region. The use of reactive oxygen species (ROS), scavenger N-acetyl cysteine (NAC) and plasma-conditioned media demonstrate that the ROS generated in the media after exposure to low-temperature plasma play a major role in these observed effects. These findings strengthen the interest in the use of MCTS for the evaluation of antiproliferative strategies, and open new perspectives for studies dedicated to demonstrate the potential of low-temperature plasma in cancer therapy.

  15. Effects of homeopathic preparations on human prostate cancer growth in cellular and animal models.

    PubMed

    MacLaughlin, Brian W; Gutsmuths, Babett; Pretner, Ewald; Jonas, Wayne B; Ives, John; Kulawardane, Don Victor; Amri, Hakima

    2006-12-01

    The use of dietary supplements for various ailments enjoys unprecedented popularity. As part of this trend, Sabal serrulata (saw palmetto) constitutes the complementary treatment of choice with regard to prostate health. In homeopathy, Sabal serrulata is commonly prescribed for prostate problems ranging from benign prostatic hyperplasia to prostate cancer. The authors' work assessed the antiproliferative effects of homeopathic preparations of Sabal serrulata, Thuja occidentalis, and Conium maculatum, in vivo, on nude mouse xenografts, and in vitro, on PC-3 and DU-145 human prostate cancer as well as MDA-MB-231 human breast cancer cell lines. Treatment with Sabal serrulata in vitro resulted in a 33% decrease of PC-3 cell proliferation at 72 hours and a 23% reduction of DU-145 cell proliferation at 24 hours (P<.01). The difference in reduction is likely due to the specific doubling time of each cell line. No effect was observed on MDA-MB-231 human breast cancer cells. Thuja occidentalis and Conium maculatum did not have any effect on human prostate cancer cell proliferation. In vivo, prostate tumor xenograft size was significantly reduced in Sabal serrulata-treated mice compared to untreated controls (P=.012). No effect was observed on breast tumor growth. Our study clearly demonstrates a biologic response to homeopathic treatment as manifested by cell proliferation and tumor growth. This biologic effect was (i)significantly stronger to Sabal serrulata than to controls and (ii)specific to human prostate cancer. Sabal serrulata should thus be further investigated as a specific homeopathic remedy for prostate pathology.

  16. Effect of the Route of Administration and PEGylation of Poly(amidoamine) Dendrimers on Their Systemic and Lung Cellular Biodistribution.

    PubMed

    Zhong, Qian; Merkel, Olivia M; Reineke, Joshua J; da Rocha, Sandro R P

    2016-06-06

    There are many opportunities in the development of oral inhalation (oi) formulations for the delivery of small molecule therapeutics and biologics to and through the lungs. Nanocarriers have the potential to play a key role in advancing oi technologies and pushing the boundary of the pulmonary delivery market. In this work we investigate the effect of the route of administration and PEGylation on the systemic and lung cellular biodistribution of generation 3, amino-terminated poly(amidoamine) (PAMAM) dendrimers (G3NH2). Pharmacokinetic profiles show that the dendrimers reach their peak concentration in systemic circulation within a few hours after pulmonary delivery, independent of their chemistry (PEGylated or not), charge (+24 mV for G3NH2 vs -3.7 mV for G3NH2-24PEG1000), or size (5.1 nm for G3NH2 and 9.9 nm for G3NH2-24PEG1000). However, high density of surface modification with PEG enhances pulmonary absorption and the peak plasma concentration upon pulmonary delivery. The route of administration and PEGylation also significantly impact the whole body and local (lung cellular) distribution of the dendrimers. While ca. 83% of G3NH2 is found in the lungs upon pulmonary delivery at 6.5 h post administration, only 2% reached the lungs upon intravenous (iv) delivery. Moreover, no measurable concentration of either G3NH2 or G3NH2-24PEG1000 is found in the lymph nodes upon iv administration, while these are the tissues with the second highest mass distribution of dendrimers post pulmonary delivery. Dendrimer chemistry also significantly impacts the (cellular) distribution of the nanocarriers in the lung tissue. Upon pulmonary delivery, approximately 20% of the lung endothelial cells are seen to internalize G3NH2-24PEG1000, compared to only 6% for G3NH2. Conversely, G3NH2 is more readily taken up by lung epithelial cells (35%) when compared to its PEGylated counterpart (24%). The results shown here suggest that both the pulmonary route of administration and dendrimer

  17. Effect of the Route of Administration and PEGylation of Poly(amidoamine) Dendrimers on Their Systemic and Lung Cellular Biodistribution

    PubMed Central

    Zhong, Qian; Merkel, Olivia M.; Reineke, Joshua J.; da Rocha, Sandro R. P.

    2017-01-01

    There are many opportunities in the development of oral inhalation (oi) formulations for the delivery of small molecule therapeutics and biologics to and through the lungs. Nanocarriers have the potential to play a key role in advancing oi technologies and pushing the boundary of the pulmonary delivery market. In this work we investigate the effect of the route of administration and PEGylation on the systemic and lung cellular biodistribution of generation 3, amino-terminated poly(amidoamine) (PAMAM) dendrimers (G3NH2). Pharmacokinetic profiles show that the dendrimers reach their peak concentration in systemic circulation within a few hours after pulmonary delivery, independent of their chemistry (PEGylated or not), charge (+24 mV for G3NH2 vs −3.7 mV for G3NH2-24PEG1000), or size (5.1 nm for G3NH2 and 9.9 nm for G3NH2-24PEG1000). However, high density of surface modification with PEG enhances pulmonary absorption and the peak plasma concentration upon pulmonary delivery. The route of administration and PEGylation also significantly impact the whole body and local (lung cellular) distribution of the dendrimers. While ca. 83% of G3NH2 is found in the lungs upon pulmonary delivery at 6.5 h post administration, only 2% reached the lungs upon intravenous (iv) delivery. Moreover, no measurable concentration of either G3NH2 or G3NH2-24PEG1000 is found in the lymph nodes upon iv administration, while these are the tissues with the second highest mass distribution of dendrimers post pulmonary delivery. Dendrimer chemistry also significantly impacts the (cellular) distribution of the nanocarriers in the lung tissue. Upon pulmonary delivery, approximately 20% of the lung endothelial cells are seen to internalize G3NH2-24PEG1000, compared to only 6% for G3NH2. Conversely, G3NH2 is more readily taken up by lung epithelial cells (35%) when compared to its PEGylated counterpart (24%). The results shown here suggest that both the pulmonary route of administration and dendrimer

  18. Cellular and synaptic effect of substance P on neonatal phrenic motoneurons.

    PubMed

    Ptak, K; Konrad, M; Di Pasquale, E; Tell, F; Hilaire, G; Monteau, R

    2000-01-01

    Experiments were carried out on the in vitro brainstem-spinal cord preparation of the newborn rat to analyse the effects of substance P (SP) on phrenic motoneuron (PMN) activity. In current-clamp mode, SP significantly depolarized PMNs, increased their input resistance, decreased the rheobase current and shifted the firing frequency-intensity relationships leftwards, but did not affect spike frequency adaptation or single spike configuration. The neurokinin receptor agonist NK1 had SP-mimetic effects, whereas the NK3 and NK2 receptor agonists were less effective and ineffective, respectively. In a tetrodotoxin-containing aCSF, only SP or the NK1 receptor agonist were still active. No depolarization was observed when the NK1 receptor agonist was applied in the presence of muscarine. In voltage-clamp mode, SP or the NK1 receptor agonist produced an inward current (ISP) which was not significantly reduced by extracellular application of tetraethylammonium, Co2+, 4-aminopyridine or Cs+. In aCSF containing tetrodotoxin, Co2+ and Cs+, ISP was blocked by muscarine. No PMN displayed any M-type potassium current but only a current showing no voltage sensitivity over the range -100 to 0 mV, reversing near the expected EK +, hence consistent with a leak current. SP application to the spinal cord only (using a partitioned chamber) significantly increased the phrenic activity. Pretreatment with the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5) decreased the C4 discharge duration and blocked the effect of SP, thus exhibiting an NMDA potentiation by SP. In conclusion, SP modulates postsynaptically the response of phrenic motoneurons to the inspiratory drive through the reduction of a leak conductance and the potentiation of the NMDA component of the synaptic input.

  19. High LET radiation shows no major cellular and functional effects on primary cardiomyocytes in vitro

    NASA Astrophysics Data System (ADS)

    Heselich, Anja; Frieß, Johannes L.; Ritter, Sylvia; Benz, Naja P.; Layer, Paul G.; Thielemann, Christiane

    2018-02-01

    It is well known that ionizing radiation causes adverse effects on various mammalian tissues. However, there is little information on the biological effects of heavy ion radiation on the heart. In order to fill this gap, we systematically examined DNA-damage induction and repair, as well as proliferation and apoptosis in avian cardiomyocyte cultures irradiated with heavy ions such as titanium and iron, relevant for manned space-flight, and carbon ions, as used for radiotherapy. Further, and to our knowledge for the first time, we analyzed the effect of heavy ion radiation on the electrophysiology of primary cardiomyocytes derived from chicken embryos using the non-invasive microelectrode array (MEA) technology. As electrophysiological endpoints beat rate and field action potential duration were analyzed. The cultures clearly exhibited the capacity to repair induced DNA damage almost completely within 24 h, even at doses of 7 Gy, and almost completely recovered from radiation-induced changes in proliferative behavior. Interestingly, no significant effects on apoptosis could be detected. Especially the functionality of primary cardiac cells exhibited a surprisingly high robustness against heavy ion radiation, even at doses of up to 7 Gy. In contrast to our previous study with X-rays the beat rate remained more or less unaffected after heavy ion radiation, independently of beam quality. The only change we could observe was an increase of the field action potential duration of up to 30% after titanium irradiation, diminishing within the following three days. This potentially pathological observation may be an indication that heavy ion irradiation at high doses could bear a long-term risk for cardiovascular disease induction.

  20. Cellular and Molecular Effect of MEHP Involving LXRα in Human Fetal Testis and Ovary

    PubMed Central

    Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N’Tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

    2012-01-01

    Background Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Methodology/Principal Findings Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10−4M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array) and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro. Conclusions/Significance We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells. PMID:23118965

  1. Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.

    PubMed

    Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N'tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

    2012-01-01

    Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4)M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array) and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro. We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.

  2. Cellular Effects of Enamel Matrix Derivative Are Associated With Specific Protein Components

    DTIC Science & Technology

    2005-05-01

    porcine teeth. Although EMD has been shown to enhance both soft tissue healing and regeneration of the periodontium, the mechanism of this action is still...to regenerate periodontal tissues that have been lost due to disease. The effectiveness of EMD has been proven both clinically and histologically in...however, a contrarian study implied that there is no difference in soft - tissue wound healing following periodontal surgery with the use of EMD (Hagenaars

  3. Mechanisms of Cellular Membrane Effects of TCDD, Selected Perfluorinated Acids and Polyhalogenated Aromatic Hydrocarbons

    DTIC Science & Technology

    1985-02-01

    toxic response of both cell lines after treatment with the perfluorinated acids ( perfluoro -n-octanoic acid, 9-H hexadecafluoro-n-nonanoic acid, and...throughout the experiments to eliminate the effect of serum on toxicity. The results for perfluoro -n-octanoic acid ( PFOA ) in both cell lines are presented in...the TK+/+ cells but not in the TK+/- cells. The results for the perfluoro -n-decanoic acid ( PFDA ) are presented in Table 3. A dose-response reldtionship

  4. Cellular uptake and anticancer effects of mucoadhesive curcumin-containing chitosan nanoparticles.

    PubMed

    Chuah, Lay Hong; Roberts, Clive J; Billa, Nashiru; Abdullah, Syahril; Rosli, Rozita

    2014-04-01

    Curcumin, which is derived from turmeric has gained much attention in recent years for its anticancer activities against various cancers. However, due to its poor absorption, rapid metabolism and elimination, curcumin has a very low oral bioavailability. Therefore, we have formulated mucoadhesive nanoparticles to deliver curcumin to the colon, such that prolonged contact between the nanoparticles and the colon leads to a sustained level of curcumin in the colon, improving the anticancer effect of curcumin on colorectal cancer. The current work entails the ex vivo mucoadhesion study of the formulated nanoparticles and the in vitro effect of mucoadhesive interaction between the nanoparticles and colorectal cancer cells. The ex vivo study showed that curcumin-containing chitosan nanoparticles (CUR-CS-NP) have improved mucoadhesion compared to unloaded chitosan nanoparticles (CS-NP), suggesting that curcumin partly contributes to the mucoadhesion process. This may lead to an enhanced anticancer effect of curcumin when formulated in CUR-CS-NP. Our results show that CUR-CS-NP are taken up to a greater extent by colorectal cancer cells, compared to free curcumin. The prolonged contact offered by the mucoadhesion of CUR-CS-NP onto the cells resulted in a greater reduction in percentage cell viability as well as a lower IC50, indicating a potential improved treatment outcome. The formulation and free curcumin appeared to induce cell apoptosis in colorectal cancer cells, by arresting the cell cycle at G2/M phase. The superior anticancer effects exerted by CUR-CS-NP indicated that this could be a potential treatment for colorectal cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Effects of PPARγ Agonist Pioglitazone on Redox-Sensitive Cellular Signaling in Young Spontaneously Hypertensive Rats

    PubMed Central

    Dovinová, Ima; Barancik, Miroslav; Zorad, Stefan; Gajdosechová, Lucia; Gresová, Linda; Cacanyiova, Sona; Kristek, Frantisek; Balis, Peter; Chan, Julie Y. H.

    2013-01-01

    PPARγ receptor plays an important role in oxidative stress response. Its agonists can influence vascular contractility in experimental hypertension. Our study was focused on the effects of a PPARγ agonist pioglitazone (PIO) on blood pressure regulation, vasoactivity of vessels, and redox-sensitive signaling at the central (brainstem, BS) and peripheral (left ventricle, LV) levels in young prehypertensive rats. 5-week-old SHR were treated either with PIO (10 mg/kg/day, 2 weeks) or with saline using gastric gavage. Administration of PIO significantly slowed down blood pressure increase and improved lipid profile and aortic relaxation after insulin stimulation. A significant increase in PPARγ expression was found only in BS, not in LV. PIO treatment did not influence NOS changes, but had tissue-dependent effect on SOD regulation and increased SOD activity, observed in LV. The treatment with PIO differentially affected also the levels of other intracellular signaling components: Akt kinase increased in the the BS, while β-catenin level was down-regulated in the BS and up-regulated in the LV. We found that the lowering of blood pressure in young SHR can be connected with insulin sensitivity of vessels and that β-catenin and SOD levels are important agents mediating PIO effects in the BS and LV. PMID:24454335

  6. The effect of selected monoterpenoids on the cellular slime mold, Dictyostelium discoideum NC4.

    PubMed

    Hwang, J Y; Kim, J H; Yun, K W

    2004-06-01

    We tested the activity of 11 main compounds identified from Pinus plants on the growth of Dictyostelium discoideum NC4. Four concentrations (1, 0.1, 0.01, 0.001 microg/microl) of each compound were tested using a disk volatilization technique following germination of D. discoideum NC4 spores. Photographs of D. discoideum NC4 fruiting bodies were taken 2 days after treatment. Fenchone (at 0.1, 0.01, and 0.001 microg/microl) and camphene (at 0.01 microg/microl) stimulated growth of D. discoideum NC4. (1S)-(-)-verbenone, (1S)-(-)-alpha-pinene, (+)-beta-pinene, myrcene, (-)-menthone, (-)-bornyl acetate, (S)-(+)-carvone, (-)-camphene, and (R)-(+)-limonene inhibit its growth. All of the compounds at 1 microg/microl had a strong inhibitory effect on cell growth of D. discoideum NC4. Microscopic observation of the fruiting bodies matched the results of growth rate analysis. Most of the inhibitory effects were represented by changes in the shapes of the fruiting bodies. These changes include short sorophores, smaller sized sori, and sori without spores. Our results suggest that inhibition of growth is the most common effect of monoterpenoids on D. discoideum NC4. Nevertheless, some of them, like fenchone and camphene, seem to enhance its growth.

  7. New insights into the biological effects of anthrax toxins: linking cellular to organismal responses

    PubMed Central

    Guichard, Annabel; Nizet, Victor; Bier, Ethan

    2013-01-01

    The anthrax toxins lethal toxin (LT) and edema toxin (ET), are essential virulence factors produced by B. anthracis. These toxins act during two distinct phases of anthrax infection. During the first, prodromal phase, which is often asymptomatic, anthrax toxins act on cells of the immune system to help the pathogen establish infection. Then, during the rapidly progressing (or fulminant) stage of the disease bacteria disseminate via a hematological route to various target tissues and organs, which are typically highly vascularized. As bacteria proliferate in the bloodstream LT and ET begin to accumulate rapidly reaching a critical threshold level that will cause death even when the bacterial proliferation is curtailed by antibiotics. During this final phase of infection the toxins cause an increase in vascular permeability and a decrease in function of target organs including the heart, spleen, kidney, adrenal gland, and brain. In this review, we examine the various biological effects of anthrax toxins, focusing on the fulminant stage of the disease and on mechanisms by which the two toxins may collaborate to cause cardiovascular collapse. We discuss normal mechanisms involved in maintaining vascular integrity and based on recent studies indicating that LT and ET cooperatively inhibit membrane trafficking to cell-cell junctions we explore several potential mechanisms by which the toxins may achieve their lethal effects. We also summarize the effects of other potential virulence factors secreted by B. anthracis and consider the role of toxic factors in the evolutionarily recent emergence of this devastating disease. PMID:21930233

  8. Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimer's Disease

    PubMed Central

    Mattioli, Roberto; Costantino, Paolo; Baima, Simona; Punzi, Pasqualina; Giordano, Cesare; Pinto, Alessandro; Donini, Lorenzo Maria; d'Erme, Maria

    2015-01-01

    β-Amyloid peptide (Aβ) aberrant production and aggregation are major factors implicated in the pathogenesis of Alzheimer's disease (AD), causing neuronal death via oxidative stress. Several studies have highlighted the importance of polyphenolic antioxidant compounds in the treatment of AD, but complex food matrices, characterized by a different relative content of these phytochemicals, have been neglected. In the present study, we analyzed the protective effect on SH-SY5Y cells treated with the fragment Aβ 25–35 by two crude juices of broccoli sprouts containing different amounts of phenolic compounds as a result of different growth conditions. Both juices protected against Aβ-induced cytotoxicity and apoptotic cell death as evidenced by cell viability, nuclear chromatin condensation, and apoptotic body formation measurements. These effects were mediated by the modulation of the mitochondrial function and of the HSP70 gene transcription and expression. Furthermore, the juices upregulated the intracellular glutathione content and mRNA levels or activity of antioxidant enzymes such as heme oxygenase-1, thioredoxin, thioredoxin reductase, and NAD(P)H:quinone oxidoreductase 1 via activation of NF-E2-related factor 2 (Nrf2). Although the effects of the two juices were similar, the juice enriched in phenolic compounds showed a greater efficacy in inducing the activation of the Nrf2 signalling pathway. PMID:26180595

  9. Apigenin attenuates streptozotocin-induced pancreatic β cell damage by its protective effects on cellular antioxidant defense.

    PubMed

    Wang, Ning; Yi, Wen Jing; Tan, Lu; Zhang, Jia Hui; Xu, Jiamin; Chen, Yi; Qin, Mengting; Yu, Shuang; Guan, Jing; Zhang, Rui

    2017-06-01

    Pancreatic beta cells are very sensitive to oxidative stress, which is one of the major causes of cell damages in diabetes. Growing interest has focused on the development of effective therapeutics to protect pancreatic cells from oxidative stress and searching for potentially protective antioxidants for treating diabetes. Apigenin, a plant-derived flavonoid, was investigated to determine whether it could protect rat insulinoma cell lines (RINm5F pancreatic beta cells) against streptozotocin (STZ)-induced oxidative damages and the mechanisms implicated. Our results showed that STZ treatment could induce oxidative stress and consequent cytotoxic effects in RINm5F cells. Pretreatment with apigenin effectively decreased the intracellular reactive oxygen species (ROS) production, attenuated cellular DNA damage, diminished lipid peroxidation, relieved protein carbonylation, and restored the cell apoptosis of pancreatic beta cells stressed by STZ. Our further experiments demonstrated that the beneficial effects of apigenin were related to ameliorate the loss of antioxidant enzymes of the STZ-treated cells in the level of gene transcription, protein expression, and enzyme activity. That suggested apigenin was not only a free radical scavenger but also a regulator to antioxidant defenses of pancreatic cells. Taken all together, our findings suggested that apigenin could attenuate the STZ-induced oxidative damages in pancreatic beta cells and might serve as a novel agent for the treatment of diabetes.

  10. Frequency Effects or Context Effects in Second Language Word Learning: What Predicts Early Lexical Production?

    ERIC Educational Resources Information Center

    Crossley, Scott A.; Subtirelu, Nicholas; Salsbury, Tom

    2013-01-01

    This study examines frequency, contextual diversity, and contextual distinctiveness effects in predicting produced versus not-produced frequent nouns and verbs by early second language (L2) learners of English. The study analyzes whether word frequency is the strongest predictor of early L2 word production independent of contextual diversity and…

  11. Effect of chirality on cellular uptake, imaging and photodynamic therapy of photosensitizers derived from chlorophyll-a.

    PubMed

    Srivatsan, Avinash; Pera, Paula; Joshi, Penny; Wang, Yanfang; Missert, Joseph R; Tracy, Erin C; Tabaczynski, Walter A; Yao, Rutao; Sajjad, Munawwar; Baumann, Heinz; Pandey, Ravindra K

    2015-07-01

    We have previously shown that the (124)I-analog of methyl 3-(1'-m-iodobenzyloxy) ethyl-3-devinyl-pyropheophorbide-a derived as racemic mixture from chlorophyll-a can be used for PET (positron emission tomography)-imaging in animal tumor models. On the other hand, as a non-radioactive analog, it showed excellent fluorescence and photodynamic therapy (PDT) efficacy. Thus, a single agent in a mixture of radioactive ((124)I-) and non-radioactive ((127)I) material can be used for both dual-imaging and PDT of cancer. Before advancing to Phase I human clinical trials, we evaluated the activity of the individual isomers as well as the impact of a chiral center at position-3(1) in directing in vitro/in vivo cellular uptake, intracellular localization, epithelial tumor cell-specific retention, fluorescence/PET imaging, and photosensitizing ability. The results indicate that both isomers (racemates), either as methyl ester or carboxylic acid, were equally effective. However, the methyl ester analogs, due to subcellular deposition into vesicular structures, were preferentially retained. All derivatives containing carboxylic acid at the position-17(2) were noted to be substrate for the ABCG2 (a member of the ATP binding cassette transporters) protein explaining their low retention in lung tumor cells expressing this transporter. The compounds in which the chirality at position-3 has been substituted by a non-chiral functionality showed reduced cellular uptake, retention and lower PDT efficacy in mice bearing murine Colon26 tumors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Effects of antioxidant, OPC-14117, on secondary cellular damage and behavioral deficits following cortical contusion in the rat.

    PubMed

    Aoyama, Naoki; Katayama, Yoichi; Kawamata, Tatsuro; Maeda, Takeshi; Mori, Tatsuro; Yamamoto, Takamitsu; Kikuchi, Tetsuro; Uwahodo, Yasuhumi

    2002-05-03

    In the present study, we examined the effects of OPC-14117, a superoxide radical scavenger, on the secondary cellular damage and cognitive dysfunction occurring in a rat model of cerebral contusion induced by a controlled cortical impact (CCI). Histological examinations revealed that the contusion necrosis volume reached 13.6+/-5.3 mm(3) in non-treated animals and declined to 1.9+/-0.6 mm(3) in OPC-14117-treated animals (P<0.01). The cell number of the CA3 region was 120.0+/-12.4 cells/mm in the normal controls, 73.6+/-9.9 cells/mm in the non-treated animals, and 111.2+/-10.2 cells/mm in the OPC-14117-treated animals, indicating that CCI-induced selective neuronal cell death in the CA3 region was attenuated by the OPC-14117 administration (P<0.01). The tissue osmolality, as determined with a vapor pressure osmometer, was 314.5+/-15.4 mmol/kg in the normal brain and increased to 426.0+/-20.1 mmol/kg at 12 h following CCI. The increase in tissue osmolality was significantly attenuated by OPC-14117 administration (P<0.01). The OPC-14117 administration also attenuated the CCI-induced cognitive deficits. The OPC-14117-treated animals showed a tendency to improve on the Morris water maze performance test. The impairment of the habituation of exploratory activity elicited by CCI was significantly attenuated by OPC-14117 administration (P<0.05). In conclusion, OPC-14117 may have a potential for decreasing secondary cellular damage due to traumatic brain injury since it is as efficacious as any other compound tested in this model.

  13. Effects of stepwise nitrogen depletion on carotenoid content, fluorescence parameters and the cellular stoichiometry of Chlorella vulgaris

    NASA Astrophysics Data System (ADS)

    Zhang, Ping; Li, Zhe; Lu, Lunhui; Xiao, Yan; Liu, Jing; Guo, Jinsong; Fang, Fang

    2017-06-01

    Stressful conditions can stimulate the accumulation of carotenoids in some microalgae. To obtain more knowledge of the stress response, we studied the effects of different N concentrations on unicellular content of carotenoids using Raman spectroscopic technique; cellular stoichiometric changes and the fluorescence parameters of Chlorella vulgaris were concomitantly studied. Initially, we optimized the Raman scattering conditions and demonstrated the feasibility of unicellular carotenoid analysis by Raman spectroscopic technique. The results showed that an integration time of 10 s, laser power at 0.1 mW and an accumulation time of 1 were the optimum conditions, and the peak height at 1523 cm- 1 scaled linearly with the carotenoid content in the range of 0.625-1440 mg/L with a recovery rate of 97% 103%. In the experiment, seven different nitrogen levels ranging from 0 to 2.48 × 105 μg/L were imposed. Samples were taken at the start, exponential phase and end of the experiment. The results showed that nitrogen stress can facilitate the synthesis of carotenoids, while at the same time, excessive nitrogen stress led to lower proliferative and photosynthetic activity. Compared with carotenoids, chlorophylls were more sensitive to nitrogen stress; it declined dramatically as stress processed. There existed no significant differences for Fv/Fm among different nitrogen levels during the exponential phase, while in the end, it declined and a significant difference appeared between cells in 2.48 × 105 μg/L N and other experimental levels. Photosynthetic efficiency, namely the C/N mole ratio in algal cells, didnot significantly change during the exponential phase; however, apparent increases ultimately occurred, except for the stable C/N in BG11 medium. This increase matched well with the carotenoid decline, indicating that an increasing cellular C/N mole ratio can be used as an indicator of excessive stress in carotenoid production. Besides, there also existed an inverse

  14. Effects of angiotensin-converting enzyme inhibitor versus valsartan on cellular signaling events in heart transplant.

    PubMed

    White, Michel; Ross, Heather; Levesque, Sylvie; Whittom, Lucette; Pelletier, Guy B; Racine, Normand; Meloche, Sylvain; Voisin, Laure

    2009-05-01

    Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) provide similar biologic effects in model systems and similar clinical impacts in humans. The changes in the cardiac angiotensin system signaling pathways in the human heart in response to ACE inhibitors versus ARBs have been incompletely studied. To investigate the effects of ACE inhibitors versus valsartan on the angiotensin II signal transduction pathways in the transplanted human heart. Twenty-seven stable cardiac transplant recipients were randomized to remain on ACE inhibitor therapy (n = 8) or to receive valsartan (n = 19). Two additional endomyocardial biopsy samples were obtained at baseline and after 9 months of therapy. The expression of cardiac angiotensin type I and II receptors and atrial natriuretic factor (ANF) was measured by quantitative polymerase chain reaction. The expression and phosphorylation levels of selected signal transduction pathways were analyzed by immunoblotting. The mean dose of valsartan was 114 +/- 41 mg/day. The use of valsartan resulted in a similar impact on blood pressure and biochemistry profile. There were no significant changes in the expression of angiotensin type I and II receptors and ANF with valsartan. Similarly, no significant changes in the expression and phosphorylation of Jun N-terminal kinase, extracellular signal-regulated kinase 1 and 2, and p38 mitogen-activated protein kinases or AKT, and mammalian target of rapamycin was observed in the valsartan-treated group. Valsartan use is associated with similar clinical and molecular cardiac effects as ACE inhibitor therapy in stable long-term cardiac transplant recipients.

  15. Controlled Breast Cancer Microarrays for the Deconvolution of Cellular Multilayering and Density Effects upon Drug Responses

    PubMed Central

    Håkanson, Maria; Kobel, Stefan; Lutolf, Matthias P.; Textor, Marcus; Cukierman, Edna; Charnley, Mirren

    2012-01-01

    Background Increasing evidence shows that the cancer microenvironment affects both tumorigenesis and the response of cancer to drug treatment. Therefore in vitro models that selectively reflect characteristics of the in vivo environment are greatly needed. Current methods allow us to screen the effect of extrinsic parameters such as matrix composition and to model the complex and three-dimensional (3D) cancer environment. However, 3D models that reflect characteristics of the in vivo environment are typically too complex and do not allow the separation of discrete extrinsic parameters. Methodology/Principal Findings In this study we used a poly(ethylene glycol) (PEG) hydrogel-based microwell array to model breast cancer cell behavior in multilayer cell clusters that allows a rigorous control of the environment. The innovative array fabrication enables different matrix proteins to be integrated into the bottom surface of microwells. Thereby, extrinsic parameters including dimensionality, type of matrix coating and the extent of cell-cell adhesion could be independently studied. Our results suggest that cell to matrix interactions and increased cell-cell adhesion, at high cell density, induce independent effects on the response to Taxol in multilayer breast cancer cell clusters. In addition, comparing the levels of apoptosis and proliferation revealed that drug resistance mediated by cell-cell adhesion can be related to altered cell cycle regulation. Conversely, the matrix-dependent response to Taxol did not correlate with proliferation changes suggesting that cell death inhibition may be responsible for this effect. Conclusions/Significance The application of the PEG hydrogel platform provided novel insight into the independent role of extrinsic parameters controlling drug response. The presented platform may not only become a useful tool for basic research related to the role of the cancer microenvironment but could also serve as a complementary platform for in

  16. Toxicity effects of di-(2-ethylhexyl) phthalate to Eisenia fetida at enzyme, cellular and genetic levels

    PubMed Central

    Chen, Li’ke; Wu, Longhua; Christie, Peter; Zhang, Haibo; Luo, Yongming

    2017-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is a dominant phthalic acid ester (PAE) that has aroused public concern due to its resistance to degradation and its toxicity as an endocrine-disrupting compound. Effects of different concentrations of DEHP on Eisenia fetida in spiked natural soil have been studied in the body of the earthworm by means of soil cultivation tests 7, 14, 21 and 28 days after exposure. The results indicated that, in general, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, metallothionein (MT) content, the expression of heat shock protein 70 (HSP 70) and all the tested geno-toxicity parameters are promoted as time elapses and with increasing concentration of DEHP. However, peroxidase (POD) activity, neutral red retention time (NRRT) and mitochondrial membrane potential difference values were found to decrease even at a low concentration of DEHP of 1 mg kg-1 soil (p<0.05). Clear toxic effects of DEHP on E. fetida have been generally recognized by means of the disturbance of antioxidant enzyme activity/content and critical proteins, cell membrane and organelle disorder and DNA damage estimated by length of tail, tail DNA ratio, and tail moment parameters. A concentration of DEHP of 3 mg kg-1 may be recommended as a precaution against the potential risk of PAEs in soils and for indicating suitable threshold values for other soil animals and soil micro-organisms. PMID:28319143

  17. Toxicity effects of di-(2-ethylhexyl) phthalate to Eisenia fetida at enzyme, cellular and genetic levels.

    PubMed

    Ma, Tingting; Zhou, Wei; Chen, Li'ke; Wu, Longhua; Christie, Peter; Zhang, Haibo; Luo, Yongming

    2017-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is a dominant phthalic acid ester (PAE) that has aroused public concern due to its resistance to degradation and its toxicity as an endocrine-disrupting compound. Effects of different concentrations of DEHP on Eisenia fetida in spiked natural soil have been studied in the body of the earthworm by means of soil cultivation tests 7, 14, 21 and 28 days after exposure. The results indicated that, in general, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, metallothionein (MT) content, the expression of heat shock protein 70 (HSP 70) and all the tested geno-toxicity parameters are promoted as time elapses and with increasing concentration of DEHP. However, peroxidase (POD) activity, neutral red retention time (NRRT) and mitochondrial membrane potential difference values were found to decrease even at a low concentration of DEHP of 1 mg kg-1 soil (p<0.05). Clear toxic effects of DEHP on E. fetida have been generally recognized by means of the disturbance of antioxidant enzyme activity/content and critical proteins, cell membrane and organelle disorder and DNA damage estimated by length of tail, tail DNA ratio, and tail moment parameters. A concentration of DEHP of 3 mg kg-1 may be recommended as a precaution against the potential risk of PAEs in soils and for indicating suitable threshold values for other soil animals and soil micro-organisms.

  18. Cellular mechanisms of desynchronizing effects of hypothermia in an in vitro epilepsy model.

    PubMed

    Motamedi, Gholam K; Gonzalez-Sulser, Alfredo; Dzakpasu, Rhonda; Vicini, Stefano

    2012-01-01

    Hypothermia can terminate epileptiform discharges in vitro and in vivo epilepsy models. Hypothermia is becoming a standard treatment for brain injury in infants with perinatal hypoxic ischemic encephalopathy, and it is gaining ground as a potential treatment in patients with drug resistant epilepsy. However, the exact mechanism of action of cooling the brain tissue is unclear. We have studied the 4-aminopyridine model of epilepsy in mice using single- and dual-patch clamp and perforated multi-electrode array recordings from the hippocampus and cortex. Cooling consistently terminated 4-aminopyridine induced epileptiform-like discharges in hippocampal neurons and increased input resistance that was not mimicked by transient receptor potential channel antagonists. Dual-patch clamp recordings showed significant synchrony between distant CA1 and CA3 pyramidal neurons, but less so between the pyramidal neurons and interneurons. In CA1 and CA3 neurons, hypothermia blocked rhythmic action potential discharges and disrupted their synchrony; however, in interneurons, hypothermia blocked rhythmic discharges without abolishing action potentials. In parallel, multi-electrode array recordings showed that synchronized discharges were disrupted by hypothermia, whereas multi-unit activity was unaffected. The differential effect of cooling on transmitting or secreting γ-aminobutyric acid interneurons might disrupt normal network synchrony, aborting the epileptiform discharges. Moreover, the persistence of action potential firing in interneurons would have additional antiepileptic effects through tonic γ-aminobutyric acid release.

  19. Differential Effects of Hormones on Cellular Metabolism in Keratoconus In Vitro

    PubMed Central

    McKay, Tina B.; Hjortdal, Jesper; Sejersen, Henrik; Karamichos, Dimitrios

    2017-01-01

    Keratoconus (KC) is a corneal thinning disease with an onset commonly immediately post-puberty and stabilization by 40 to 50 years of age. The role of hormones in regulating corneal tissue structure in homeostatic and pathological conditions is unknown. Our group recently linked altered hormone levels to KC. Our current study sought to investigate and delineate the effects of exogenous hormones, such as androgen, luteotropin, and estrogen, on corneal stroma bioenergetics. We utilized our established 3D in vitro model to characterize the effects of DHEA, prolactin, 17β-estradiol on insulin-growth factor-1 and -2 (IGF-1, -2) signaling and metabolic function in primary corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs). Our data showed that exogenous DHEA significantly downregulated IGF-1 and its receptor in both HCFs and HKCs with HKCs showing consistently lower basal pentose phosphate flux. Prolactin caused no significant change in IGF-1 levels and an increase in IGF-2 in HKCs correlating with an increase in ATP and NADH levels. 17β-estradiol led to a significant upregulation in pentose phosphate flux and glycolytic intermediates in HCFs. Our results identified hormone-specific responses regulated in HKCs compared to HCFs revealing a novel role for hormones on bioenergetics in KC. PMID:28211546

  20. Muramyl peptides in mammalian tissues and their effects at the cellular level.

    PubMed

    Karnovsky, M L

    1986-10-01

    Muramyl peptides (MPs), presumably breakdown products of bacterial cell walls, have been found in the brain, liver, and kidney of the rat. They exert multiple physiological effects on higher animals as immunoadjuvants, activators of macrophages, pyrogens, antitumor agents, inducers of contractility of smooth muscle, and promoters of slow-wave sleep, as well as nonspecific protectors of animals against infection. Structure-function relationships of these substances have been extensively studied, especially with respect to somnogenicity. In the role an intact muramyl ring is required, and the 1,6-anhydro form is active. The presence of free carboxyls or amides on the glutamyl and diaminopimelyl entities have important effects. The stereochemistry is crucial: the alanine adjacent to the N-acetylmuramyl entity must be L, and the glutamate must be D. Studies were carried out with murine macrophages to establish mechanisms of action of these glycopeptides. There are two populations of binding sites for MPs on those cells. When compounds of different structure are compared, binding ability correlates with pyrogenic and somnogenic activity. Serotonin competes with these agents for binding sites. Binding of that substance induces at least one macrophage response characteristic of the binding of MP.

  1. In vitro toxicology of ambient particulate matter: correlation of cellular effects with particle size and components.

    PubMed

    Kroll, Alexandra; Gietl, Johanna K; Wiesmüller, Gerhard A; Günsel, Andreas; Wohlleben, Wendel; Schnekenburger, Jürgen; Klemm, Otto

    2013-02-01

    High concentrations of airborne particulate matter (PM) have been associated with increased rates of morbidity and mortality among exposed populations. Although certain components of PM were suggested to influence these effects, no clear-cut correlation was determined thus far. One of the possible modes of action is the induction of oxidative stress by inhaled PM triggering inflammatory responses. Therefore, the in vitro formation of reactive oxygen species (ROS) in three cell lines in the presence of five subfractions of PM(10), collected in Münster, Germany was investigated. The PM components chloride, nitrate, ammonium, sulfate, 68 chemical elements, and endotoxin were quantified. The highest concentration of endotoxin was found in particles of 0.42-1.2 μm aerodynamic diameters, and therefore probably subject to long-range transport. Intracellular ROS formation in three well established mammalian cell lines (CaCo2, human; MDCK, canine; RAW264.7, mouse) only correlated positively with particle size. The two smallest PM size fractions provoked the highest rise in ROS. However, the latter did not correlate with the concentration of any PM components investigated. The smallest PM size fractions significantly dominated the number of particles. Therefore, the particle number may be most effective in inducing oxidative stress in vitro. Copyright © 2011 Wiley Periodicals, Inc.

  2. Effects of primitive photosynthesis on Earth's early climate system

    NASA Astrophysics Data System (ADS)

    Ozaki, Kazumi; Tajika, Eiichi; Hong, Peng K.; Nakagawa, Yusuke; Reinhard, Christopher T.

    2018-01-01

    The evolution of different forms of photosynthetic life has profoundly altered the activity level of the biosphere, radically reshaping the composition of Earth's oceans and atmosphere over time. However, the mechanistic impacts of a primitive photosynthetic biosphere on Earth's early atmospheric chemistry and climate are poorly understood. Here, we use a global redox balance model to explore the biogeochemical and climatological effects of different forms of primitive photosynthesis. We find that a hybrid ecosystem of H2-based and Fe2+-based anoxygenic photoautotrophs—organisms that perform photosynthesis without producing oxygen—gives rise to a strong nonlinear amplification of Earth's methane (CH4) cycle, and would thus have represented a critical component of Earth's early climate system before the advent of oxygenic photosynthesis. Using a Monte Carlo approach, we find that a hybrid photosynthetic biosphere widens the range of geochemical conditions that allow for warm climate states well beyond either of these metabolic processes acting in isolation. Our results imply that the Earth's early climate was governed by a novel and poorly explored set of regulatory feedbacks linking the anoxic biosphere and the coupled H, C and Fe cycles. We suggest that similar processes should be considered when assessing the potential for sustained habitability on Earth-like planets with reducing atmospheres.

  3. Physiological effects and cellular responses of metamorphic larvae and juveniles of sea urchin exposed to ionic and nanoparticulate silver.

    PubMed

    Magesky, Adriano; Ribeiro, Ciro A Oliveiro; Pelletier, Émilien

    2016-05-01

    The widespread use of silver nanoparticles (AgNPs) would likely result in their discharge into wastewater and inevitable release in densely populated coastal areas. It is known that AgNPs can cause harmful effects to marine fauna, but how they affect development stages is still an open question. In order to understand in details how polymer-coated AgNPs (PAAm-AgNPs) (from 0.19 to 4.64mM as Ag) can affect critical stages of marine invertebrate development, metamorphic larvae and juveniles of sea urchins were used as biological models. Multidimensional scaling (MDS) approach based on Bray-Curtis similarity matrix with PERMANOVA showed organisms in a multivariate space undergoing through different physiological conditions as a function of time, chemical forms of silver, nominal concentrations, and presence or absence of food. Sublethal effects such as lethargy, oedema and immobility mainly characterized PAAm-AgNPs effects with juveniles and postlarvae, whereas necrosis and death arose in Ag(+) conditions in short-term tests. Chronically exposed metamorphic larvae had their morphogenic processes interrupted by PAAm-AgNPs and a high mortality rate was observed in recovery period. On the contrary, Ag(+) ions caused progressive mortality during exposure, but a quick recovery in uncontaminated seawater was observed. By means of fluorescent markers we showed that nanosilver could be transferred between consecutive stages (swimming larvae and postlarvae) and highlighted how important is food to enhance PAAm-AgNPs uptake. Using TEM we observed that unfed juveniles had nanosilver aggregates mostly restricted to their coelomic sinuses, while metamorphic larvae already had nano-contamination overspread in different tissues and blastocoel. Our main hypothesis for nanotoxicity of PAAM-AgNPs relies on the slow dissolution of nano-core over time, but in this study the effects of particulate silver form itself are also evoked. Main mechanisms governing tissular and cellular responses

  4. Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

    SciTech Connect

    Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp; Umeda, Sachiko; Yasuda, Takeshi

    2014-02-01

    Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation withmore » γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can

  5. Effects of intraperitoneal and intranasal application of Lentinan on cellular response in rats.

    PubMed

    Markova, Nadya; Kussovski, Vesselin; Radoucheva, Tatyana; Dilova, Krasimira; Georgieva, Neli

    2002-11-01

    Lentinan (Ajinomoto, Japan) was administrated intraperitoneally (i.p.) and intranasally (i.n.) at different doses (1, 5 and 10 mg/kg) to rats. Effectiveness of Lentinan treatment was evaluated by comparative testing of cell activation (establishing the number, glycolytic and acid phosphatase activity, H2O2 production and killing ability against Salmonella enteritidis and Staphylococcus aureus) at two different compartments--peritoneal and broncho-alveolar cavities. The results indicated that Lentinan induced high-grade activation of peritoneal cells (PCs) and especially of broncho-alveolar cells (BACs) with markedly enhanced effector function (killing ability against S. aureus). Generally, Lentinan, known usually with its parenteral routes of application, can be successful to stimulate the host cell response in the respiratory tract by intranasal route of administration.

  6. Parvovirus particles and movement in the cellular cytoplasm and effects of the cytoskeleton

    SciTech Connect

    Lyi, Sangbom Michael; Tan, Min Jie Alvin, E-mail: tanmja@gis.a-star.edu.sg; Parrish, Colin R., E-mail: crp3@cornell.edu

    2014-05-15

    Cell infection by parvoviruses requires that capsids be delivered from outside the cell to the cytoplasm, followed by genome trafficking to the nucleus. Here we microinject capsids into cells that lack receptors and followed their movements within the cell over time. In general the capsids remained close to the positions where they were injected, and most particles did not move to the vicinity of or enter the nucleus. When 70 kDa-dextran was injected along with the capsids that did not enter the nucleus in significant amounts. Capsids conjugated to peptides containing the SV40 large T-antigen nuclear localization signal remained inmore » the cytoplasm, although bovine serum albumen conjugated to the same peptide entered the nucleus rapidly. No effects of disruption of microfilaments, intermediate filaments, or microtubules on the distribution of the capsids were observed. These results suggest that movement of intact capsids within cells is primarily associated with passive processes.« less

  7. Molecular and cellular mechanisms underlying the therapeutic effects of budesonide in asthma.

    PubMed

    Pelaia, Girolamo; Vatrella, Alessandro; Busceti, Maria Teresa; Fabiano, Francesco; Terracciano, Rosa; Matera, Maria Gabriella; Maselli, Rosario

    2016-10-01

    Inhaled glucocorticoids are the mainstay of asthma treatment. Indeed, such therapeutic agents effectively interfere with many pathogenic circuits underpinning asthma. Among these drugs, during the last decades budesonide has been probably the most used molecule in both experimental studies and clinical practice. Therefore, a large body of evidence clearly shows that budesonide, either alone or in combination with long-acting bronchodilators, provides a successful control of asthma in many patients ranging throughout the overall spectrum of disease severity. These excellent therapeutic properties of budesonide basically depend on its molecular mechanisms of action, capable of inhibiting within the airways the activity of multiple immune-inflammatory and structural cells involved in asthma pathobiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Clinical pharmacology of CAR-T cells: Linking cellular pharmacodynamics to pharmacokinetics and antitumor effects.

    PubMed

    Norelli, M; Casucci, M; Bonini, C; Bondanza, A

    2016-01-01

    Adoptive cell transfer of T cells genetically modified with tumor-reactive chimeric antigen receptors (CARs) is a rapidly emerging field in oncology, which in preliminary clinical trials has already shown striking antitumor efficacy. Despite these premises, there are still a number of open issues related to CAR-T cells, spanning from their exact mechanism of action (pharmacodynamics), to the factors associated with their in vivo persistence (pharmacokinetics), and, finally, to the relative contribution of each of the two in determining the antitumor effects and accompanying toxicities. In light of the unprecedented curative potential of CAR-T cells and of their predicted wide availability in the next few years, in this review we will summarize the current knowledge on the clinical pharmacology aspects of what is anticipated to be a brand new class of biopharmaceuticals to join the therapeutic armamentarium of cancer doctors. Copyright © 2015. Published by Elsevier B.V.

  9. Evaluation of the effects of a freeze/thaw environment on cellular glass

    NASA Technical Reports Server (NTRS)

    Frickland, P.; Cleland, E.; Hasegawa, T.

    1981-01-01

    Using the evaluation criteria of water vapor permeability and conformability, a protective butylrubber/silicone conformal coating system was selected for use on Foamglas substrates in a freeze/thaw environment. The selection of a specific freeze/thaw cycle which closely models field conditions is discussed. A sampling plan is described which allows independent evaluation of the effects of conformal coatings, cycle number and location within the environmental chamber. The results of visual examination, measurement of density, modulus of rupture and Young's modulus are reported. Based upon statistical evaluation of the experimental results, it is concluded that no degradation in mechanical properties of either coated or uncoated Foamglas occurred within the duration of the test (53 freeze/thaw cycles).

  10. Predicting Glucose Sensor Behavior in Blood Using Transport Modeling: Relative Impacts of Protein Biofouling and Cellular Metabolic Effects

    PubMed Central

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

    2013-01-01

    Background Tissue response to indwelling glucose sensors remains a confounding barrier to clinical application. While the effects of fully formed capsular tissue on sensor response have been studied, little has been done to understand how tissue interactions occurring before capsule formation hinder sensor performance. Upon insertion in subcutaneous tissue, the sensor is initially exposed to blood, blood borne constituents, and interstitial fluid. Using human whole blood as a simple ex vivo experimental system, the effects of protein accumulation at the sensor surface (biofouling effects) and cellular consumption of glucose in both the biofouling layer and in the bulk (metabolic effects) on sensor response were assessed. Methods Medtronic MiniMed SofSensor glucose sensors were incubated in whole blood, plasma-diluted whole blood, and cell-free platelet-poor plasma (PPP) to analyze the impact of different blood constituents on sensor function. Experimental conditions were then simulated using MATLAB to predict the relative impacts of biofouling and metabolic effects on the observed sensor responses. Results Protein biofouling in PPP in both the experiments and the simulations was found to have no interfering effect upon sensor response. Experimental results obtained with whole and dilute blood showed that the sensor response was markedly affected by blood borne glucose-consuming cells accumulated in the biofouling layer and in the surrounding bulk. Conclusions The physical barrier to glucose transport presented by protein biofouling does not hinder glucose movement to the sensor surface, and the consumption of glucose by inflammatory cells, and not erythrocytes, proximal to the sensor surface has a substantial effect on sensor response and may be the main culprit for anomalous sensor behavior immediately following implantation. PMID:24351181

  11. The harmful effects of ethanol on ion transport and cellular respiration.

    PubMed

    Blachley, J D; Johnson, J H; Knochel, J P

    1985-01-01

    The deleterious effects of ethanol on a variety of tissues may result largely from altered ion permeabilities and transport. Clinically relevant ethanol concentrations in blood increase the sodium permeability of the plasma membrane and depress active sodium transport by suppressing Na, K-ATPase activity. As a result, intracellular sodium concentration increases. The total tissue content of calcium increases. Important transport mechanisms deranged by ethanol probably include those regulating calcium-sodium and hydrogen-sodium exchange at the plasma membrane and calcium uptake by the sarcoplasmic reticulum. A modest decline in magnesium content of muscle occurs after chronic exposure to ethanol. This also has been associated with accumulation of calcium. After days to weeks of sustained ethanol intake, sodium pump activity, active sodium transport and tissue oxygen consumption increase. The cell membrane potential, initially lowered by alcohol, increases to supraphysiological levels. This is likely an electrogenic effect of increased sodium transport in response to a sodium leak. Eventually the earlier derangements in tissue composition, including retention of sodium, chloride, and calcium, and reductions in magnesium, potassium, and phosphate, slowly undergo correction. This biphasic response of injury and adaptation appears to depend upon adequate nutrition and the absence of other factors that can adversely affect cell function. That the Na, K-ATPase activity and oxygen consumption remain elevated suggests an ongoing sodium leak of the sarcolemmal membrane. Chronic ethanol-induced cell necrosis may be related to the increased intracellular calcium that accompanies the increase in sodium permeability. Conceivably, critically elevated concentrations of calcium in the cytoplasm may activate autolytic enzymes that in turn may be responsible for structural damage to the cell.

  12. The Cellular State Determines the Effect of Melatonin on the Survival of Mixed Cerebellar Cell Culture

    PubMed Central

    Franco, Daiane Gil; Markus, Regina P.

    2014-01-01

    The constitutive activation of nuclear factor-κB (NF-κB), a key transcription factor involved in neuroinflammation, is essential for the survival of neurons in situ and of cerebellar granule cells in culture. Melatonin is known to inhibit the activation of NF-κB and has a cytoprotective function. In this study, we evaluated whether the cytoprotective effect of melatonin depends on the state of activation of a mixed cerebellar culture that is composed predominantly of granule cells; we tested the effect of melatonin on cultured rat cerebellar cells stimulated or not with lipopolysaccharide (LPS). The addition of melatonin (0.1 nM–1 µM) reduced the survival of naïve cells while inhibiting LPS-induced cell death. Melatonin (100 nM) transiently (15 min) inhibited the nuclear translocation of both NF-κB dimers (p50/p50, p50/RelA) and, after 60 min, increased the activation of p50/RelA. Melatonin-induced p50/RelA activity in naïve cells resulted in the transcription of inducible nitric oxide synthase (iNOS) and the production of NO. Otherwise, in cultures treated with LPS, melatonin blocked the LPS-induced activation of p50/RelA and the reduction in p50/p50 levels and inhibited iNOS expression and NO synthesis. Therefore, melatonin in vehicle-treated cells induces cell death, while it protects against LPS-induced cytotoxicity. In summary, we confirmed that melatonin is a neuroprotective drug when cerebellar cells are challenged; however, melatonin can also lead to cell death when the normal balance of the NF-κB pathway is disturbed. Our data provide a mechanistic basis for understanding the influence of cell context on the final output response of melatonin. PMID:25184316

  13. Alterations of erythrocyte rheology and cellular susceptibility in end stage renal disease: Effects of peritoneal dialysis.

    PubMed

    Ertan, Nesrin Zeynep; Bozfakioglu, Semra; Ugurel, Elif; Sinan, Mukaddes; Yalcin, Ozlem

    2017-01-01

    In this study, we investigated the effects of peritoneal dialysis on hemorheological and hematological parameters and their relations with oxidant and antioxidant status of uremic patients. Hemorheological parameters (erythrocyte deformability, erythrocyte aggregation, osmotic deformability, blood and plasma viscosity) were measured in patients with renal insufficiency undergoing peritoneal dialysis (PD) and volunteers. Erythrocyte deformability, osmotic deformability and aggregation in both autologous plasma and 3% dextran 70 were measured by laser diffraction ektacytometry. Enzyme activities of glutathione peroxidase, superoxide dismutase and catalase were studied in erythrocytes; lipid peroxidation was studied by measuring the amount of malondialdehyde in both erythrocytes and plasma samples. Blood viscosity at native hematocrit was significantly lower in PD patients at all measured shear rates compared to controls, but it was high in PD patients at corrected (45%) hematocrit. Erythrocyte deformability did not show any difference between the two groups. Osmotic deformability was significantly lower in PD patients compared to controls. Aggregation index values were significantly high in PD patients in plasma Catalase and glutathione peroxidase activities in erythrocytes were decreased in PD patients whereas superoxide dismutase activity was increased compared to controls. Malondialdehyde was significantly increased in erythrocytes and plasma samples of PD patients which also shows correlations with aggregation parameters. It has been concluded that erythrocytes in PD patients are more prone to aggregation and this tendency could be influenced by lipid peroxidation activity in patient's plasma. These results imply that uremic conditions, loss of plasma proteins and an increased risk of oxidative stress because of decreasing levels of antioxidant enzymes affect erythrocyte rheology during peritoneal dialysis. This level of distortion may have crucial effects

  14. Potential toxic effect of trifloxystrobin on cellular microstructure, mRNA expression and antioxidant enzymes in Chlorella vulgaris.

    PubMed

    Shen, Yu-Feng; Liu, Lei; Gong, Yu-Xin; Zhu, Bin; Liu, Guang-Lu; Wang, Gao-Xue

    2014-05-01

    This study investigated the effects of trifloxystrobin that one strobilurin used widely in the world as an effective fungicidal agent to control Asian soybean rust on aquatic unicellular algae Chlorella vulgaris. We determined the potential toxic effect of trifloxystrobin on C. vulgaris, and found median inhibition concentration (IC(50)) value 255.58 (95% confidence interval, 207.81-330.29)μgL(-1). In addition, the algal cells were obviously depressed or shrunk at different concentrations by electron microscopy. In the study, a real-time polymerase chain reaction (PCR) assay showed changes in transcript abundances of three photosynthetic genes, psaB, psbC, and rbcL, and one energy gene, ATPs. The results showed that trifloxystrobin reduced the transcript abundances of the three genes and enhanced expression of ATPs after 48 and 96 h. The lowest abundances of psaB, psbC and rbcL transcripts in response to trifloxystrobin exposure were 58%, 79% and 60% of those of the control, respectively. For the potential toxic influences, trifloxystrobin could decrease the soluble protein and total antioxidant contents (T-AOC), and increase superoxide dismutase (SOD) and peroxidase (POD) activity with a gradual concentration-response relationship. Overall, the present study demonstrated that trifloxystrobin could affect the activities of antioxidant enzymes, disrupts photosynthesis in C. vulgaris, and damage cellular structure. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. [Effectiveness of an early discharge program after normal childbirth].

    PubMed

    Teulón González, M; Martínez Pillado, M; Cuadrado Martín, M M; Rivero Martín, M J; Cerezuela Requena, J F

    To implement a program of early hospital discharge after an uncomplicated birth, in order to improve the effectiveness, as well as ensuring clinical safety and patient acceptability. Descriptive study of the effectiveness of an early discharge program after uncomplicated delivery between February 2012 and September 2013. The populations are post-partum women and newborns admitted to the University Hospital of Fuenlabrada, with a duration of less than 24h after uncomplicated delivery that met the defined inclusion criteria. Satisfaction was assessed using a Likert scale. The effectiveness of the program was monitored by safety indicators, productivity, adaptation, and continuity of care. A total of 20% of cases capable of early discharge from Fuenlabrada University Hospital completed the program. Almost all (94%) were normal deliveries. The 188 cases included were from 911 patients with uncomplicated childbirth, accounting for 6.5% of the 2,857 total births. The mean stay of patients included showed a decrease of 50% (2.4 to 1.2 days). All patients received continuity of care after hospital discharge. The review consultation was reprogrammed for 4.8% of cases, with 2% of patients re-admitted within 96h. with no serious problems. Four newborns (2%) required attention in the emergency department (mother or newborn) before 96h. The assessment of patient satisfaction achieved a score of 4.5 out of 5. The program achieved a decrease in the average stay by 50%, favouring the autonomy of midwives. This acceptance level is in line with similar interventions. The deployment of the program may be useful for other changes in care processes. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Effects of Gravity, Microgravity or Microgravity Simulation on Early Mammalian Development.

    PubMed

    Ruden, Douglas M; Bolnick, Alan; Awonuga, Awoniyi; Abdulhasan, Mohammed; Perez, Gloria; Puscheck, Elizabeth E; Rappolee, Daniel A

    2018-06-11

    Plant and animal life forms evolved mechanisms for sensing and responding to gravity on Earth where homeostatic needs require responses. The lack of gravity, such as in the International Space Station (ISS), causes acute, intra-generational changes in the quality of life. These include maintaining calcium levels in bone, maintaining muscle tone, and disturbances in the vestibular apparatus in the ears. These problems decrease work efficiency and quality of life of humans not only during microgravity exposures but also after return to higher gravity on Earth or destinations such as Mars or the Moon. It has been hypothesized that lack of gravity during mammalian development may cause prenatal, postnatal and transgenerational effects that conflict with the environment, especially if the developing organism and its progeny are returned, or introduced de novo, into the varied gravity environments mentioned above. Although chicken and frog pregastrulation development, and plant root development, have profound effects due to orientation of cues by gravity-sensing mechanisms and responses, mammalian development is not typically characterized as gravity-sensing. Although no effects of microgravity simulation (MGS) on mouse fertilization were observed in two reports, negative effects of MGS on early mammalian development after fertilization and before gastrulation are presented in four reports that vary with the modality of MGS. This review will analyze the positive and negative mammalian early developmental outcomes, and enzymatic and epigenetic mechanisms known to mediate developmental responses to simulated microgravity on Earth and microgravity during spaceflight experiments. We will update experimental techniques that have already been developed or need to be developed for zero gravity molecular, cellular, and developmental biology experiments.

  17. Equitable service provision for inclusive education and effective early intervention.

    PubMed

    Wicks, K M

    1998-01-01

    This paper illustrates one model of providing an integrated paediatric speech and language therapy service which attempts to meet the demands of both inclusive education and effective early intervention. A move has been made from location-oriented therapy provision to offering children and their families equal opportunities to have appropriate intervention according to need. The model incorporates the philosophy of inclusive education and supports the development of current specialist educational establishments into resource bases of expertise for children with special needs in mainstream schools.

  18. Anticancer Properties of PPARα-Effects on Cellular Metabolism and Inflammation

    PubMed Central

    Grabacka, Maja; Reiss, Krzysztof

    2008-01-01

    Peroxisome proliferator-activated receptors (PPARs) have lately attracted much attention as therapeutic targets. Previously, PPAR ligands were associated with the treatment of diabetes, hyperlipidemia and cardiovascular diseases, as they modulate the expression of genes regulating glucose and lipid metabolism. Recently, PPAR ligands have been also considered as potential anticancer agents, with relatively low systemic toxicity. The emerging evidence for antiproliferative, proapoptotic, antiinflammatory and potential antimetastatic properties of PPARα ligands prompted us to discuss possible roles of PPARα in tumor suppression. PPARα activation can target cancer cells energy balance by blocking fatty acid synthesis and by promoting fatty acid β-oxidation. In the state of limited nutrient availability, frequently presents in the tumor microenvironment, PPARα cooperates with AMP-dependent protein kinase in: (i) repressing oncogenic Akt activity, (ii) inhibiting cell proliferation, and (iii) forcing glycolysis-dependent cancer cells into “metabolic catastrophe.” Other potential anticancer effects of PPARα include suppression of inflammation, and upregulation of uncoupling proteins (UCPs), which attenuates mitochondrial reactive oxygen species production and cell proliferation. In conclusion, there are strong premises that the low-toxic and well-tolerated PPAR ligands should be considered as new therapeutic agents to fight disseminating cancer, which represents the major challenge for modern medicine and basic research. PMID:18509489

  19. Cellular immunocompetence in melanoma: effect of extent of disease and immunotherapy.

    PubMed Central

    Lui, V. K.; Karpuchas, J.; Dent, P. B.; McCulloch, P. B.; Blajchman, M. A.

    1975-01-01

    Cell mediated immunocompetence was measured serially in 35 patients with malignant melanoma in order to determine the effect of extent of disease and prognosis as well as the influence of BCG immunotherapy on immune reactivity. Compared with normal adult controls, statistically significant lymphopenia occurred only in patients with widespread disease. Seventeen of 21 patients with negative pre-therapy PPD skin test converted to skin test positivity. PHA blastogenesis was depressed only in patients in the pre-terminal stages of their disease using optimal mitogen concentrations for stimulation. Threshold concentrations of this mitogen more clearly demonstrated a depressed responsiveness which correlated in severity with extent of disease. PPD induced blastogenesis was normal or increased in the majority of patients; however, the degree of stimulation by PPD was less in the BCG induced convertors than in those patients who were skin test positive before BCG treatment. Comparison of the pre- and post BCG assessments reveals no significant differences except in relation to PPD conversion. We conclude that using threshold concentrations of PHA, impaired responses are regularly associated with disease beyond the regional lymph nodes. Routine assessment of lymphocyte function by these parameters did not provide information that was not available from clinical evaluation. PMID:1233077

  20. Effects of protein kinase inhibitors on in vitro protein phosphorylation and cellular differentiation of Streptomyces griseus.

    PubMed

    Hong, S K; Matsumoto, A; Horinouchi, S; Beppu, T

    1993-01-01

    In vitro phosphorylation reactions using extracts of Streptomyces griseus cells and gamma-[32P]ATP revealed the presence of multiple phosphorylated proteins. Most of the phosphorylations were distinctly inhibited by staurosporine and K-252a which are known to be eukaryotic protein kinase inhibitors. The in vitro experiments also showed that phosphorylation was greatly enhanced by manganese and inhibition of phosphorylation by staurosporine and K-252a was partially circumvented by 10 mM manganese. A calcium-activated protein kinase(s) was little affected by these inhibitors. Herbimycin and radicicol, known to be tyrosine kinase inhibitors, completely inhibited the phosphorylation of one protein. Consistent with their in vitro effects the protein kinase inhibitors inhibited aerial mycelium formation and pigment production by S. griseus. All these data suggest that S. griseus possesses several protein kinases of eukaryotic type which are essential for morphogenesis and secondary metabolism. In vitro phosphorylation of some proteins in a staurosporine-producing Streptomyces sp. was also inhibited by staurosporine, K-252a and herbimycin, which suggests the presence of a mechanism for self-protection in this microorganism.

  1. Extension of TOPAS for the simulation of proton radiation effects considering molecular and cellular endpoints

    PubMed Central

    Polster, Lisa; Schuemann, Jan; Rinaldi, Ilaria; Burigo, Lucas; McNamara, Aimee L.; Stewart, Robert D.; Attili, Andrea; Carlson, David J.; Sato, Tatsuhiko; Méndez, José Ramos; Faddegon, Bruce; Perl, Joseph; Paganetti, Harald

    2015-01-01

    The aim of this work is to extend a widely used proton Monte Carlo tool, TOPAS, towards the modeling of relative biological effect (RBE) distributions in experimental arrangements as well as patients. TOPAS provides a software core which users configure by writing parameter files to, for instance, define application specific geometries and scoring conditions. Expert users may further extend TOPAS scoring capabilities by plugging in their own additional C++ code. This structure was utilized for the implementation of eight biophysical models suited to calculate proton RBE. As far as physics parameters are concerned, four of these models are based on the proton linear energy transfer (LET), while the others are based on DNA Double Strand Break (DSB) induction and the frequency-mean specific energy, lineal energy, or delta electron generated track structure. The biological input parameters for all models are typically inferred from fits of the models to radiobiological experiments. The model structures have been implemented in a coherent way within the TOPAS architecture. Their performance was validated against measured experimental data on proton RBE in a spread-out Bragg peak using V79 Chinese Hamster cells. This work is an important step in bringing biologically optimized treatment planning for proton therapy closer to the clinical practice as it will allow researchers to refine and compare pre-defined as well as user-defined models. PMID:26061666

  2. Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer.

    PubMed

    Thomas, T J; Thomas, Thresia

    2018-03-13

    Polyamine levels are elevated in breast tumors compared to those of adjacent normal tissues. The female sex hormone, estrogen is implicated in the origin and progression of breast cancer. Estrogens stimulate and antiestrogens suppress the expression of polyamine biosynthetic enzyme, ornithine decarboxylate (ODC). Using several bis(ethyl)spermine analogues, we found that these analogues inhibited the proliferation of estrogen receptor-positive and estrogen receptor negative breast cancer cells in culture. There was structure-activity relationship in the efficacy of these compounds in suppressing cell growth. The activity of ODC was inhibited by these compounds, whereas the activity of the catabolizing enzyme, spermidine/spermine N ¹-acetyl transferase (SSAT) was increased by 6-fold by bis(ethyl)norspermine in MCF-7 cells. In a transgenic mouse model of breast cancer, bis(ethyl)norspermine reduced the formation and growth of spontaneous mammary tumor. Recent studies indicate that induction of polyamine catabolic enzymes SSAT and spermine oxidase (SMO) play key roles in the anti-proliferative and apoptotic effects of polyamine analogues and their combinations with chemotherapeutic agents such as 5-fluorouracil (5-FU) and paclitaxel. Thus, polyamine catabolic enzymes might be important therapeutic targets and markers of sensitivity in utilizing polyamine analogues in combination with other therapeutic agents.

  3. Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer

    PubMed Central

    Thomas, Thresia

    2018-01-01

    Polyamine levels are elevated in breast tumors compared to those of adjacent normal tissues. The female sex hormone, estrogen is implicated in the origin and progression of breast cancer. Estrogens stimulate and antiestrogens suppress the expression of polyamine biosynthetic enzyme, ornithine decarboxylate (ODC). Using several bis(ethyl)spermine analogues, we found that these analogues inhibited the proliferation of estrogen receptor-positive and estrogen receptor negative breast cancer cells in culture. There was structure-activity relationship in the efficacy of these compounds in suppressing cell growth. The activity of ODC was inhibited by these compounds, whereas the activity of the catabolizing enzyme, spermidine/spermine N1-acetyl transferase (SSAT) was increased by 6-fold by bis(ethyl)norspermine in MCF-7 cells. In a transgenic mouse model of breast cancer, bis(ethyl)norspermine reduced the formation and growth of spontaneous mammary tumor. Recent studies indicate that induction of polyamine catabolic enzymes SSAT and spermine oxidase (SMO) play key roles in the anti-proliferative and apoptotic effects of polyamine analogues and their combinations with chemotherapeutic agents such as 5-fluorouracil (5-FU) and paclitaxel. Thus, polyamine catabolic enzymes might be important therapeutic targets and markers of sensitivity in utilizing polyamine analogues in combination with other therapeutic agents. PMID:29533973

  4. Effects of ozone on the respiratory health, allergic sensitization, and cellular immune system in children

    SciTech Connect

    Zwick, H.; Popp, W.; Wagner, C.

    1991-11-01

    To investigate the lasting effects of high ozone concentrations under environmental conditions, we examined the respiratory health, pulmonary function, bronchial hyperresponsiveness to methacholine, allergic sensitization, and lymphocyte subpopulations of 10- to 14-yr-old children. A total of 218 children recruited from an area with high ozone concentrations (Group A) were tested against 281 children coming from an area with low ozone concentrations (Group B). As to subjective complaints, categorized as 'usually cough with or without phlegm,' 'breathlessness,' and 'susceptibility to chest colds,' there was no difference between the two groups. The lung function parameters were similar, but in Group A subjects'more » bronchial hyperresponsiveness occurred more frequently and was found to be more severe than in Group B (29.4 versus 19.9%, p less than 0.02; PD20 2,100 {plus minus} 87 versus 2,350 {plus minus} 58 micrograms, p less than 0.05). In both groups the number of children who had been suffering from allergic diseases and sensitization to aeroallergens, found by means of the skin test, was the same. Comparison of the total IgE levels showed no difference at all between the two groups. As far as the white blood cells are concerned, the total and differential cell count was the same, whereas lymphocyte subpopulations showed readily recognizable changes.« less

  5. Extension of TOPAS for the simulation of proton radiation effects considering molecular and cellular endpoints

    NASA Astrophysics Data System (ADS)

    Polster, Lisa; Schuemann, Jan; Rinaldi, Ilaria; Burigo, Lucas; McNamara, Aimee L.; Stewart, Robert D.; Attili, Andrea; Carlson, David J.; Sato, Tatsuhiko; Ramos Méndez, José; Faddegon, Bruce; Perl, Joseph; Paganetti, Harald

    2015-07-01

    The aim of this work is to extend a widely used proton Monte Carlo tool, TOPAS, towards the modeling of relative biological effect (RBE) distributions in experimental arrangements as well as patients. TOPAS provides a software core which users configure by writing parameter files to, for instance, define application specific geometries and scoring conditions. Expert users may further extend TOPAS scoring capabilities by plugging in their own additional C++ code. This structure was utilized for the implementation of eight biophysical models suited to calculate proton RBE. As far as physics parameters are concerned, four of these models are based on the proton linear energy transfer, while the others are based on DNA double strand break induction and the frequency-mean specific energy, lineal energy, or delta electron generated track structure. The biological input parameters for all models are typically inferred from fits of the models to radiobiological experiments. The model structures have been implemented in a coherent way within the TOPAS architecture. Their performance was validated against measured experimental data on proton RBE in a spread-out Bragg peak using V79 Chinese Hamster cells. This work is an important step in bringing biologically optimized treatment planning for proton therapy closer to the clinical practice as it will allow researchers to refine and compare pre-defined as well as user-defined models.

  6. Biochemical Characterization and Cellular Effects of CADASIL Mutants of NOTCH3

    PubMed Central

    Meng, He; Zhang, Xiaojie; Yu, Genggeng; Lee, Soo Jung; Chen, Y. Eugene; Prudovsky, Igor; Wang, Michael M.

    2012-01-01

    Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the best understood cause of dominantly inherited stroke and results from NOTCH3 mutations that lead to NOTCH3 protein accumulation and selective arterial smooth muscle degeneration. Previous studies show that NOTCH3 protein forms multimers. Here, we investigate protein interactions between NOTCH3 and other vascular Notch isoforms and characterize the effects of elevated NOTCH3 on smooth muscle gene regulation. We demonstrate that NOTCH3 forms heterodimers with NOTCH1, NOTCH3, and NOTCH4. R90C and C49Y mutant NOTCH3 form complexes which are more resistant to detergents than wild type NOTCH3 complexes. Using quantitative NOTCH3-luciferase clearance assays, we found significant inhibition of mutant NOTCH3 clearance. In coculture assays of NOTCH function, overexpressed wild type and mutant NOTCH3 significantly repressed NOTCH-regulated smooth muscle transcripts and potently impaired the activity of three independent smooth muscle promoters. Wildtype and R90C recombinant NOTCH3 proteins applied to cell cultures also blocked canonical Notch fuction. We conclude that CADASIL mutants of NOTCH3 complex with NOTCH1, 3, and 4, slow NOTCH3 clearance, and that overexpressed wild type and mutant NOTCH3 protein interfere with key NOTCH-mediated functions in smooth muscle cells. PMID:23028706

  7. Cytotoxic effects of Mn(III) N-alkylpyridylporphyrins in the presence of cellular reductant, ascorbate

    PubMed Central

    Ye, Xiaodong; Fels, Diane; Tovmasyan, Artak; Aird, Katherine M.; Dedeugd, Casey; Allensworth, Jennifer L.; Kos, Ivan; Park, Won; Spasojevic, Ivan; Devi, Gayathri R.; Dewhirst, Mark W.; Leong, Kam W.; Batinic-Haberle, Ines

    2012-01-01

    Due to the ability to easily accept and donate electrons Mn(III) N-alkylpyridylporphyrins (MnPs) can dismute O2˙−, reduce peroxynitrite, but also generate reactive species and behave as pro-oxidants if conditions favour such action. Herein two ortho isomers, MnTE-2-PyP5+, MnTnHex-2-PyP5+, and a meta isomer MnTnHex-3-PyP5+, which differ greatly with regard to their metal-centered reduction potential, E1/2 (MnIIIP/MnIIP) and lipophilicity, were explored. Employing MnIIIP/MnIIP redox system for coupling with ascorbate, these MnPs catalyze ascorbate oxidation and thus peroxide production. Consequently, cancer oxidative burden may be enhanced, which in turn would suppress its growth. Cytotoxic effects on Caco-2, Hela, 4T1, HCT116 and SUM149 were studied. When combined with ascorbate, MnPs killed cancer cells via peroxide produced outside of the cell. MnTE-2-PyP5+ was the most efficacious catalyst for peroxide production, while MnTnHex-3-PyP5+ is most prone to oxidative degradation with H2, and thus the least efficacious. A 4T1 breast cancer mouse study of limited scope and success was conducted. The tumour oxidative stress was enhanced and its microvessel density reduced when mice were treated either with ascorbate or MnP/ascorbate; the trend towards tumour growth suppression was detected. PMID:21859376

  8. Cellular mechanisms underlying the effects of milrinone and cilostazol to suppress arrhythmogenesis associated with Brugada syndrome.

    PubMed

    Szél, Tamás; Koncz, István; Antzelevitch, Charles

    2013-11-01

    Brugada syndrome is an inherited disease associated with vulnerability to ventricular tachycardia and sudden cardiac death in young adults. Milrinone and cilostazol, oral phosphodiesterase (PDE) type III inhibitors, have been shown to increase L-type calcium channel current (ICa) and modestly increase heart rate by elevating the level of intracellular cyclic adenosine monophosphate. To examine the effectiveness of these PDE inhibitors to suppress arrhythmogenesis in an experimental model of Brugada syndrome. Action potential (AP) and electrocardiographic recordings were obtained from epicardial and endocardial sites of coronary-perfused canine right ventricular wedge preparations. The Ito agonist NS5806 (5 μM) and Ca(2+) channel blocker verapamil (2 μM) were used to pharmacologically mimic Brugada phenotype. The combination induced all-or-none repolarization at some epicardial sites but not others, leading to ST-segment elevation as well as an increase in both epicardial and transmural dispersion of repolarization. Under these conditions, phase 2 reentry developed as the epicardial AP dome propagated from sites where it was maintained to sites at which it was lost, generating closely coupled extrasystoles and ventricular tachycardia. The addition of the PDE inhibitor milrinone (2.5 μM) or cilostazol (5-10 μM) to the coronary perfusate restored the epicardial AP dome, reduced dispersion, and abolished phase 2 reentry-induced extrasystoles and ventricular tachycardia. Our study identifies milrinone as a more potent alternative to cilostazol for reversing the repolarization defects responsible for the electrocardiographic and arrhythmic manifestations of Brugada syndrome. Both drugs normalize ST-segment elevation and suppress arrhythmogenesis in experimental models of Brugada syndrome. © 2013 Heart Rhythm Society. All rights reserved.

  9. Cellular Mechanisms Underlying the Effects of Milrinone and Cilostazol to Suppress Arrhythmogenesis Associated with Brugada Syndrome

    PubMed Central

    Szél, Tamás; Koncz, István; Antzelevitch, Charles

    2013-01-01

    Background: Brugada syndrome is an inherited disease associated with vulnerability to ventricular tachycardia and sudden cardiac death in young adults. Milrinone and cilostazol, oral phosphodiesterase (PDE) type III inhibitors, have been shown to increase ICa and modestly increase heart rate by elevating the level of intracellular cyclic AMP. Objective: The present study examines the effectiveness of these PDE inhibitors to suppress arrhythmogenesis in an experimental model of Brugada syndrome. Methods: Action potential (AP) and ECG recordings were obtained from epicardial and endocardial sites of coronary-perfused canine right ventricular wedge preparations. The Ito agonist NS5806 (5 μM) and Ca2+ channel blocker verapamil (2 μM) were used to pharmacologically mimic Brugada phenotype. Results: The combination induced all-or-none repolarization at some epicardial sites but not others, leading to ST-segment elevation as well as an increase in both epicardial and transmural dispersion of repolarization. Under these conditions, phase 2 reentry developed as the epicardial AP dome propagated from sites where it was maintained to sites at which it was lost, generating closely coupled extrasystoles and ventricular tachycardia. Addition of the PDE inhibitor milrinone (2.5 μM) or cilostazol (5-10 μM) to the coronary perfusate restored the epicardial AP dome, reduced dispersion and abolished phase 2 reentry—induced extrasystoles and ventricular tachycardia. Conclusions: Our study identifies milrinone as a more potent alternative to cilostazol for reversing the repolarization defects responsible for the electrocardiographic and arrhythmic manifestations of Brugada syndrome. Both drugs normalize ST segment elevation, and suppress arrhythmogenesis in experimental models of Brugada syndrome. PMID:23911896

  10. Effect of Lower and Upper Body High Intensity Training on Genes Associated with Cellular Stress Response

    PubMed Central

    Kochanowicz, Andrzej; Kochanowicz, Kazimierz; Mieszkowski, Jan; Niespodziński, Bartłomiej; Sawczyn, Stanisław

    2017-01-01

    This study aimed to compare the effect of upper and lower body high intensity exercise (HIE) on select gene expression in athletes. Fourteen elite male artistic gymnasts (age 20.9 ± 2.6 years; weight 68.6 ± 7.2 kg; fat free mass 63.6 ± 6.7 kg; height 1.70 ± 0.04 m) performed lower and upper body 30 s Wingate Tests (WAnTs) before and after eight weeks of specific HIIT. Two milliliters of blood was collected before and after (5, 30 min, resp.) lower and upper body WAnTs, and select gene expression was determined by PCR. Eight weeks of HIIT caused a significant increase in maximal power (722 to 751 Wat), relative peak power in the lower body WAnTs (10.1 to 11 W/kg), mean power (444 to 464 W), and relative mean power (6.5 to 6.8 W/kg). No significant differences in lower versus upper body gene expression were detected after HIIT, and a significant decrease in the IL6/IL10 ratio was observed after lower (−2∧0.57 p = 0.0019) and upper (−2∧0.5 p = 0.03) WAnTs following eight weeks of HIIT. It is hypothesized that a similar adaptive response to exercise may be obtained by lower and upper body exercise. PMID:28589135

  11. Time-dependent observation of individual cellular binding events to field-effect transistors.

    PubMed

    Schäfer, S; Eick, S; Hofmann, B; Dufaux, T; Stockmann, R; Wrobel, G; Offenhäusser, A; Ingebrandt, S

    2009-01-01

    Electrolyte-gate field-effect transistors (EG-FETs) gained continuously more importance in the field of bioelectronics. The reasons for this are the intrinsic properties of these FETs. Binding of analysts or changes in the electrolyte composition are leading to variations of the drain-source current. Furthermore, due to the signal amplification upon voltage-to-current conversion even small extracellular signals can be detected. Here we report about impedance spectroscopy with an FET array to characterize passive components of a cell attached to the transistor gate. We developed a 16-channel readout system, which provides a simultaneous, lock-in based readout. A test signal of known amplitude and phase was applied via the reference electrode. We monitored the electronic transfer function of the FETs with the attached cell. The resulting frequency spectrum was used to investigate the surface adhesion of individual HEK293 cells. We applied different chemical treatments with either the serinpeptidase trypsin or the ionophor amphotericin B (AmpB). Binding studies can be realized by a time-dependent readout of the lock-in amplifier at a constant frequency. We observed cell detachment upon trypsin activity as well as membrane decomposition induced by AmpB. The results were interpreted in terms of an equivalent electrical circuit model of the complete system. The presented method could in future be applied to monitor more relevant biomedical manipulations of individual cells. Due to the utilization of the silicon technology, our method could be easily up-scaled to many output channels for high throughput pharmacological screening.

  12. Effects of Spaceflight on Molecular and Cellular Responses to Bleomycin-induced DNA Damages in Confluent Human Fibroblasts

    NASA Astrophysics Data System (ADS)

    Lu, Tao; Wu, Honglu; Karouia, Fathi; Stodieck, Louis; Zhang, Ye; Wong, Michael

    2016-07-01

    Spaceflights expose human beings to various risk factors. Among them are microgravity related physiological stresses in immune, cytoskeletal, and cardiovascular systems, and space radiation related elevation of cancer risk. Cosmic radiation consists of energetic protons and other heavier charged particles that induce DNA damages. Effective DNA damage response and repair mechanism is important to maintain genomic integrity and reduce cancer risk. There were studies on effects of spaceflight and microgravity on DNA damage response in cell and animal models, but the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on molecular and cellular responses to DNA damages, bleomycin, an anti-cancer drug and radiomimetic reagent, was used to induce DNA damages in confluent human fibroblasts flown to the International Space Station (ISS) and on ground. After exposure to 1.0 mg/ml bleomycin for 3 hours, cells were fixed for immunofluorescence assays and for RNA preparation. Extents of DNA damages were quantified by focus pattern and focus number counting of phosphorylated histone protein H2AX (γg-H2AX). The cells on the ISS showed modestly increased average focus counts per nucleus while the distribution of patterns was similar to that on the ground. PCR array analysis showed that expressions of several genes, including CDKN1A and PCNA, were significantly changed in response to DNA damages induced by bleomycin in both flight and ground control cells. However, there were no significant differences in the overall expression profiles of DNA damage response genes between the flight and ground samples. Analysis of cellular proliferation status with Ki-67 staining showed a slightly higher proliferating population in cells on the ISS than those on ground. Our results suggested that the difference in γg-H2AX focus counts between flight and ground was due to the higher percentage of proliferating cells in space, but spaceflight did not

  13. Effective cellular internalization, cell cycle arrest and improved pharmacokinetics of Tamoxifen by cholesterol based lipopolymeric nanoparticles.

    PubMed

    Mazumdar, Samrat; Italiya, Kishan S; Sharma, Saurabh; Chitkara, Deepak; Mittal, Anupama

    2018-05-30

    nanoparticles offer a more promising approach for delivery of Tamoxifen in breast cancer by improving drug internalization and prolonging the mean residence time of the drug indicating possibility of dose reduction and hence bypassing the adverse effects of TMX therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Cellular effects of mitomycin-C on human corneas after photorefractive keratectomy.

    PubMed

    Rajan, Madhavan S; O'Brart, David P S; Patmore, Anne; Marshall, John

    2006-10-01

    To investigate the effects of mitomycin-C (MMC) on epithelial and keratocyte cell kinetics after photorefractive keratectomy (PRK) using an in vitro human cornea model. Department of Academic Ophthalmology, Rayne Institute, St. Thomas' Hospital, London, United Kingdom. Twenty-four human eye-bank corneas were placed in a specially designed acrylic corneal holder and cultured using the air-interface organ culture technique for up to 4 weeks. The corneas were divided into 3 groups. Group 1 consisted of 8 human corneas that had -9.00 diopter (D) myopic PRK without MMC application. Group 2 consisted of 8 corneas that had -9.00 D PRK with MMC (0.2 microg/mL) application for 1 minute on the stromal surface after ablation. Group 3 consisted of 8 corneas that had -9.00 D PRK with 2-minute exposure to MMC (0.2 microg/mL). Temporal events in epithelial and keratocyte cell kinetics were evaluated using digital imaging, confocal microscopy, and light microscopy. Epithelial latency was significantly delayed with MMC application in Groups 2 and 3 (P<.001). Epithelial migration was delayed in Group 3 (2-minute exposure) compared to migration in Group 2 (P<.04), with a consequent delay in epithelial closure (P<.001). Group 3 corneas had poorly differentiated epithelium that was significantly thinner than in Groups 1 and 2 (P<.0001). A significant delay in keratocyte regeneration occurred after MMC application (P<.0005). At 4 weeks, the anterior stromal cell density was significantly lower in Group 3 than Group 2 (P<.001). There were no significant differences in the mid- and posterior stromal keratocyte density between the groups. Results suggest that epithelial healing after MMC is characterized by prolonged latency and decreased migration rate dependent on exposure time. Mitomycin C application did not result in increased loss of keratocytes, but it significantly delayed keratocyte repopulation in the anterior stroma. The use of MMC 0.2 microg/mL for 1 minute resulted in optimum

  15. Adrenoceptors in Brain: Cellular Gene Expression and Effects on Astrocytic Metabolism and [Ca2+]i

    PubMed Central

    Hertz, Leif; Lovatt, Ditte; Goldman, Steven A.; Nedergaard, Maiken

    2010-01-01

    Recent in vivo studies have established astrocytes as a major target for locus coeruleus activation (Bekar et al., Cereb. Cortex 18, 2789–2795), renewing interest in cell culture studies on noradrenergic effects on astrocytes in primary cultures and calling for additional information about the expression of adrenoceptor subtypes on different types of brain cells. In the present communication, mRNA expression of α1-, α2- and β-adrenergic receptors and their subtypes was determined in freshly-isolated, cell marker-defined populations of astrocytes, NG2-positive cells, microglia, endothelial cells, and Thy1-positive neurons (mainly glutamatergic projection neurons) in murine cerebral cortex. Immediately after dissection of frontal, parietal and occipital cortex of 10–12-week-old transgenic mice, which combined each cell-type marker with a specific fluorescent signal, the tissue was digested, triturated and centrifuged, yielding a solution of dissociated cells of all types, which were separated by fluorescence-activated cell sorting (FACS). mRNA expression in each cell fraction was determined by microarray analysis. α1A-Receptors were unequivocally expressed in astrocytes and NG2-positive cells, but absent in other cell types, and α1B-receptors were not expressed in any cell population. Among α2-receptors only α2A-receptors were expressed, unequivocally in astrocytes and NG-positive cells, tentatively in microglia and questionably in Thy1-positive neurons and endothelial cells. β1-Receptors were unequivocally expressed in astrocytes, tentatively in microglia, and questionably in neurons and endothelial cells, whereas β2-adrenergic receptors showed tentative expression in neurons and astrocytes and unequivocal expression in other cell types. This distribution was supported by immunochemical data and its relevance established by previous studies in well-differentiated primary cultures of mouse astrocytes, showing that stimulation of α2-adrenoceptors

  16. Effects of genistein on early-stage cutaneous wound healing

    SciTech Connect

    Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected bymore » antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These

  17. Late effects of early growth hormone treatment in Down syndrome.

    PubMed

    Myrelid, Å; Bergman, S; Elfvik Strömberg, M; Jonsson, B; Nyberg, F; Gustafsson, J; Annerén, G

    2010-05-01

    Down syndrome (DS) is associated with short stature and psychomotor delay. We have previously shown that growth hormone (GH) treatment during infancy and childhood normalizes growth velocity and improves fine motor skill performance in DS. The aim of this study was to investigate late effects of early GH treatment on growth and psychomotor development in the DS subjects from the previous trial. Twelve of 15 adolescents with DS (3 F) from the GH group and 10 of 15 controls (5 F) participated in this follow-up study. Fifteen other subjects with DS (6 F) were included as controls in anthropometric analyses. Cognitive function was assessed with the Leiter International Performance Scale-Revised (Leiter-R) and selected subtests of the Wechsler Intelligence Scale for Children, Third edition (WISC-III). The Bruininks-Oseretsky Test of Motor Proficiency, Second edition (BOT-2), was used to assess general motor ability. Although early GH treatment had no effect on final height, the treated subjects had a greater head circumference standard deviation score (SDS) than the controls (-1.6 SDS vs. -2.2 SDS). The adolescents previously treated with GH had scores above those of the controls in all subtests of Leiter-R and WISC-III, but no difference in Brief IQ-score was seen between the groups. The age-adjusted motor performance of all subjects was below -2 SD, but the GH-treated subjects performed better than the controls in all but one subtest. The combined finding of a greater head circumference SDS and better psychomotor performance indicates that DS subjects may benefit from early GH treatment.

  18. Dual effects of fluoxetine on mouse early embryonic development.

    PubMed

    Kim, Chang-Woon; Choe, Changyong; Kim, Eun-Jin; Lee, Jae-Ik; Yoon, Sook-Young; Cho, Young-Woo; Han, Sunkyu; Tak, Hyun-Min; Han, Jaehee; Kang, Dawon

    2012-11-15

    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50μM) for different durations. When late 2-cells were incubated with 5μM fluoxetine for 6h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetine (5μM) over 24h showed a reduction in blastocyst formation. The addition of fluoxetine (5μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K(+) channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ~30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Effects of nicotine on cellular proliferation, macromolecular synthesis and cell cycle phase distribution in human and murine cells

    SciTech Connect

    Konno, S.; Chiao, J.; Rossi, J.

    1986-05-01

    Addition of nicotine causes a dose- and time-dependent inhibition of cell growth in established human and murine cells. In the human promyelocytic HL-60 leukemic cells, 3 mM nicotine results in a 50% inhibition of cellular proliferation after 80 h. Nicotine was also found to affect the cell cycle distribution of HL-60 cells. Treatment with 4 mM nicotine for 20 h causes an increase in proportion of Gl-phase cells (from 49% to 57%) and a significant decrease in the proportion of S-phase cells (from 41% to 32%). These results suggest that nicotine causes cell arrest in the Gl-phase which may inmore » part account for its effects on cell growth. To determine whether nicotine has a primary effect on the uptake/transport of macromolecular precursors into cells, HL-60 cells were treated with 2-6 mM nicotine for 30 h/sub 3/ at the end of which time cells were labeled with (/sup 3/H)thymidine, (/sup 3/H)uridine, (/sup 14/C)lysine and (/sup 35/S)methionine, the trichloroacetic acid (TCA) soluble and insoluble radioactivities from each of the labeling conditions were determined. These studies show that nicotine primarily affect the synthesis of proteins.« less

  20. Coupled elasticity–diffusion model for the effects of cytoskeleton deformation on cellular uptake of cylindrical nanoparticles

    PubMed Central

    Wang, Jizeng; Li, Long

    2015-01-01

    Molecular dynamic simulations and experiments have recently demonstrated how cylindrical nanoparticles (CNPs) with large aspect ratios penetrate animal cells and inevitably deform cytoskeletons. Thus, a coupled elasticity–diffusion model was adopted to elucidate this interesting biological phenomenon by considering the effects of elastic deformations of cytoskeleton and membrane, ligand–receptor binding and receptor diffusion. The mechanism by which the binding energy drives the CNPs with different orientations to enter host cells was explored. This mechanism involved overcoming the resistance caused by cytoskeleton and membrane deformations and the change in configurational entropy of the ligand–receptor bonds and free receptors. Results showed that deformation of the cytoskeleton significantly influenced the engulfing process by effectively slowing down and even hindering the entry of the CNPs. Additionally, the engulfing depth was determined quantitatively. CNPs preferred or tended to vertically attack target cells until they were stuck in the cytoskeleton as implied by the speed of vertically oriented CNPs that showed much faster initial engulfing speeds than horizontally oriented CNPs. These results elucidated the most recent molecular dynamics simulations and experimental observations on the cellular uptake of carbon nanotubes and phagocytosis of filamentous Escherichia coli bacteria. The most efficient engulfment showed the stiffness-dependent optimal radius of the CNPs. Cytoskeleton stiffness exhibited more significant influence on the optimal sizes of the vertical uptake than the horizontal uptake. PMID:25411410

  1. Coupled elasticity-diffusion model for the effects of cytoskeleton deformation on cellular uptake of cylindrical nanoparticles.

    PubMed

    Wang, Jizeng; Li, Long

    2015-01-06

    Molecular dynamic simulations and experiments have recently demonstrated how cylindrical nanoparticles (CNPs) with large aspect ratios penetrate animal cells and inevitably deform cytoskeletons. Thus, a coupled elasticity-diffusion model was adopted to elucidate this interesting biological phenomenon by considering the effects of elastic deformations of cytoskeleton and membrane, ligand-receptor binding and receptor diffusion. The mechanism by which the binding energy drives the CNPs with different orientations to enter host cells was explored. This mechanism involved overcoming the resistance caused by cytoskeleton and membrane deformations and the change in configurational entropy of the ligand-receptor bonds and free receptors. Results showed that deformation of the cytoskeleton significantly influenced the engulfing process by effectively slowing down and even hindering the entry of the CNPs. Additionally, the engulfing depth was determined quantitatively. CNPs preferred or tended to vertically attack target cells until they were stuck in the cytoskeleton as implied by the speed of vertically oriented CNPs that showed much faster initial engulfing speeds than horizontally oriented CNPs. These results elucidated the most recent molecular dynamics simulations and experimental observations on the cellular uptake of carbon nanotubes and phagocytosis of filamentous Escherichia coli bacteria. The most efficient engulfment showed the stiffness-dependent optimal radius of the CNPs. Cytoskeleton stiffness exhibited more significant influence on the optimal sizes of the vertical uptake than the horizontal uptake. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  2. Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations.

    PubMed

    Yadav, Monu; Jindal, Deepak Kumar; Dhingra, Mamta Sachdeva; Kumar, Anil; Parle, Milind; Dhingra, Sameer

    2018-04-01

    Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.

  3. The effect of tunicamycin on the glucose uptake, growth, and cellular adhesion in the protozoan parasite Crithidia fasciculata.

    PubMed

    Rojas, Robert; Segovia, Christopher; Trombert, Annette Nicole; Santander, Javier; Manque, Patricio

    2014-10-01

    Crithidia fasciculata represents a very interesting model organism to study biochemical, cellular, and genetic processes unique to members of the family of the Trypanosomatidae. Thus, C. fasciculata parasitizes several species of insects and has been widely used to test new therapeutic strategies against parasitic infections. By using tunicamycin, a potent inhibitor of glycosylation in asparaginyl residues of glycoproteins (N-glycosylation), we demonstrate that N-glycosylation in C. fasciculata cells is involved in modulating glucose uptake, dramatically impacting growth, and cell adhesion. C. fasciculata treated with tunicamycin was severely affected in their ability to replicate and to adhere to polystyrene substrates and losing their ability to aggregate into small and large groups. Moreover, under tunicamycin treatment, the parasites were considerably shorter and rounder and displayed alterations in cytoplasmic vesicles formation. Furthermore, glucose uptake was significantly impaired in a tunicamycin dose-dependent manner; however, no cytotoxic effect was observed. Interestingly, this effect was reversible. Thus, when tunicamycin was removed from the culture media, the parasites recovered its growth rate, cell adhesion properties, and glucose uptake. Collectively, these results suggest that changes in the tunicamycin-dependent glycosylation levels can influence glucose uptake, cell growth, and adhesion in the protozoan parasite C. fasciculata.

  4. Effects of hypotonic stress and ouabain on the apparent diffusion coefficient of water at cellular and tissue levels in Aplysia.

    PubMed

    Jelescu, Ileana Ozana; Ciobanu, Luisa; Geffroy, Françoise; Marquet, Pierre; Le Bihan, Denis

    2014-03-01

    There is evidence that physiological or pathological cell swelling is associated with a decrease of the apparent diffusion coefficient (ADC) of water in tissues, as measured with MRI. However the mechanism remains unclear. Magnetic resonance microscopy, performed on small tissue samples, has the potential to distinguish effects occurring at cellular and tissue levels. A three-dimensional diffusion prepared fast imaging with steady-state free precession sequence for MR microscopy was implemented on a 17.2 T imaging system and used to investigate the effect of two biological challenges known to cause cell swelling, exposure to a hypotonic solution or to ouabain, on Aplysia nervous tissue. The ADC was measured inside isolated neuronal soma and in the region of cell bodies of the buccal ganglia. Both challenges resulted in an ADC increase inside isolated neuronal soma (+31 ± 24% and +30 ± 11%, respectively) and an ADC decrease at tissue level in the buccal ganglia (-12 ± 5% and -18 ± 8%, respectively). A scenario involving a layer of water molecules bound to the inflating cell membrane surface is proposed to reconcile this apparent discrepancy. Copyright © 2014 John Wiley & Sons, Ltd.

  5. The German ISS-Experiment Cellular Responses to Radiation in Space (CERASP): The Effects of Single and Combined Space Flight Conditions on Mammalian Cells

    NASA Astrophysics Data System (ADS)

    Baumstark-Khan, C.; Hellweg, C. E.; Arenz, A.

    The combined action of ionizing radiation and microgravity will continue to influence future space missions with special risks for astronauts on the Moon surface or for long duration missions to Mars Previous space flight experiments have reported additive neither sensitization nor protection as well as synergistic increased radiation effect under microgravity interactions of radiation and microgravity in different cell systems Although a direct effect of microgravity on enzymatic mechanisms can be excluded on thermo dynamical reasons modifications of cellular repair can not be excluded as such processes are under the control of cellular signal transduction systems which are controlled by environmental parameters presumably also by gravity DNA repair studies in space on bacteria yeast cells and human fibroblasts which were irradiated before flight gave contradictory results from inhibition of repair by microgravity to enhancement whereas others did not detect any influence of microgravity on repair At the Radiation Biology Department of the German Aerospace Center DLR recombinant bacterial and mammalian cell systems were developed as reporters for cellular signal transduction modulation by genotoxic environmental conditions The space experiment CERASP Cellular Responses to Radiation in Space to be performed at the International Space Station ISS will make use of such reporter cell lines thereby supplying basic information on the cellular response to radiation applied in microgravity One of the biological endpoints will be survival

  6. Global/temporal gene expression analysis of Escherichia coli in the early stages of symbiotic relationship development with the cellular slime mold Dictyostelium discoideum.

    PubMed

    Kihara, Kumiko; Mori, Kotaro; Suzuki, Shingo; Ono, Naoaki; Furusawa, Chikara; Yomo, Tetsuya

    2009-05-01

    Escherichia coli and the cellular slime mold Dictyostelium discoideum form stable viscous symbiotic colonies in the laboratory. To examine changes in E. coli gene expression during establishment of this symbiotic relationship, cells of symbiotic co-cultures and monocultures at various time points were subjected to microarrays analysis. Genes changed significantly over time compared to the initial gene expression level were determined as characteristics of GO function categories. The categories that appeared significantly at the same sampling time points between the two cultures were also identified. Up-regulation of genes from several GO categories associated with polysaccharide synthesis, cell wall degradation, and iron acquisition as well as down-regulation of genes from GO categories associated with biosynthesis through starvation response were observed in co-cultures, indicating exchange of molecules between the two organisms. Up-regulation of genes from several GO categories associated with anaerobic respiration and flagella biosynthesis were also observed, indicating that the environment inside symbiotic colonies was similar to that in developed biofilms. Up-regulation of genes associated with energy-generating systems indicated that E. coli prolonged survival within the symbiotic colony. Thus, E. coli showed not only molecule exchange but also altered expression of various genes in symbiosis with D. discoideum.

  7. Aggressive effects of prioritizing popularity in early adolescence.

    PubMed

    Cillessen, Antonius H N; Mayeux, Lara; Ha, Thao; de Bruyn, Eddy H; LaFontana, Kathryn M

    2014-01-01

    This study examined the moderating effects of prioritizing popularity on the association between early adolescents' popularity and their aggressive, leadership, and prosocial behaviors with peers. Participants were 288 14-year-olds from The Netherlands who completed a sociometric instrument and an assessment of how much they prioritized popularity over other personal goals. Results indicated that prioritizing popularity was distinct from actual popularity in the peer group. Further, prioritizing popularity moderated the association of popularity with aggressive and leadership behaviors, with adolescents who were both popular and who prioritized popularity being particularly aggressive and scoring high on leadership behaviors. This trend was especially true for boys. The same moderating effect was not found for prosocial behaviors. Motivational and social-cognitive factors in the dynamics of peer popularity are highlighted. © 2013 Wiley Periodicals, Inc.

  8. Early effects of duloxetine on emotion recognition in healthy volunteers

    PubMed Central

    Bamford, Susan; Penton-Voak, Ian; Pinkney, Verity; Baldwin, David S; Munafò, Marcus R; Garner, Matthew

    2015-01-01

    The serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine is an effective treatment for major depression and generalised anxiety disorder. Neuropsychological models of antidepressant drug action suggest therapeutic effects might be mediated by the early correction of maladaptive biases in emotion processing, including the recognition of emotional expressions. Sub-chronic administration of duloxetine (for two weeks) produces adaptive changes in neural circuitry implicated in emotion processing; however, its effects on emotional expression recognition are unknown. Forty healthy participants were randomised to receive either 14 days of duloxetine (60 mg/day, titrated from 30 mg after three days) or matched placebo (with sham titration) in a double-blind, between-groups, repeated-measures design. On day 0 and day 14 participants completed a computerised emotional expression recognition task that measured sensitivity to the six primary emotions. Thirty-eight participants (19 per group) completed their course of tablets and were included in the analysis. Results provide evidence that duloxetine, compared to placebo, may reduce the accurate recognition of sadness. Drug effects were driven by changes in participants’ ability to correctly detect subtle expressions of sadness, with greater change observed in the placebo relative to the duloxetine group. These effects occurred in the absence of changes in mood. Our preliminary findings require replication, but complement recent evidence that sadness recognition is a therapeutic target in major depression, and a mechanism through which SNRIs could resolve negative biases in emotion processing to achieve therapeutic effects. PMID:25759400

  9. Effects of zoledronic acid and geranylgeraniol on the cellular behaviour and gene expression of primary human alveolar osteoblasts.

    PubMed

    Zafar, S; Coates, D E; Cullinan, M P; Drummond, B K; Milne, T; Seymour, G J

    2016-11-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication of bisphosphonate therapy. The mechanism underlying BRONJ pathogenesis is poorly understood. To determine the effects of zoledronic acid (ZA) and geranylgeraniol (GGOH) on the mevalonate pathway (MVP) in osteoblasts generated from the human mandibular alveolar bone in terms of cell viability/proliferation, migration, apoptosis and gene expression. Primary human osteoblasts (HOBs) isolated from the mandibular alveolar bone were phenotyped. HOBs were cultured with or without ZA and GGOH for up to 72 h. Cellular behaviour was examined using a CellTiter-Blue® viability assay, an Ibidi culture-insert migration assay, an Apo-ONE® Homogeneous Caspase-3/7 apoptosis assay and transmission electron microscopy (TEM). Quantitative real-time reverse transcriptase polymerase chain reaction (qRT 2 -PCR) was used to determine the simultaneous expression of 168 osteogenic and angiogenic genes modulated in the presence of ZA and GGOH. ZA decreased cell viability and migration and induced apoptosis in HOBs. TEM revealed signs of apoptosis in ZA-treated HOBs. However, the co-addition of GGOH ameliorated the effect of ZA and partially restored the cells to the control state. Twenty-eight genes in the osteogenic array and 27 genes in the angiogenic array were significantly regulated in the presence of ZA compared with those in the controls at one or more time points. The cytotoxic effect of ZA on HOBs and its reversal by the addition of GGOH suggests that the effect of ZA on HOBs is mediated via the MVP. The results suggest that GGOH could be used as a possible therapeutic/preventive strategy for BRONJ.

  10. Climatic and Chemical Effects of Punctuated Volcanism on Early Mars

    NASA Astrophysics Data System (ADS)

    Halevy, I.; Head, J. W.

    2012-12-01

    The geological record of Mars shows a pronounced peak in volcanic activity during the transition between the late Noachian and early Hesperian epochs. This peak appears coeval with profound climatic and chemical changes in the surface environment, including the formation of the majority of known valley networks, open-basin lakes and the deposition of massive sulfate-bearing deposits of aqueous origin. It has been suggested that volcanism maintained a warmer climate and an active hydrological cycle through the radiative effect of volcanically emitted greenhouse gases, such as CO2, H2O and SO2. However, previous model attempts at explaining overland flow with CO2-H2O greenhouse atmospheres required several bars of CO2, even including the warming effect of infrared scattering by CO2 ice clouds. This amount of CO2 is in apparent disagreement with recent estimates of volcanic outgassing on Mars. The net climatic effect of volcanic SO2 emissions into the atmosphere of early Mars has been the topic of recent debate, because it is unclear whether strong greenhouse warming by SO2 or strong cooling by scattering sulfate aerosols should dominate. To address this problem, we considered two previously neglected phenomena: i) the punctuated, rather than continuous, nature of volcanic eruptions, and ii) the role of preexisting dust grains and volcanic ash as condensation nuclei for sulfuric acid. For this purpose we developed a coupled model of volcanic eruption and atmospheric response, including detailed aerosol microphysics. We find that while SO2 concentrations increase rapidly and dramatically with the initiation of a strong volcanic eruption, the dynamics of sulfate aerosol formation in the martian atmosphere results in a delay of aerosol-related cooling by several months to years. Moreover, the existence of dust in the atmosphere prior to the volcanic eruption, as well as the emission and global distribution of fine volcanic ash particles, results in the formation of H2SO4

  11. Dual effects of fluoxetine on mouse early embryonic development

    SciTech Connect

    Kim, Chang-Woon; Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University, Changwon 630-723; Choe, Changyong

    2012-11-15

    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50 μM) for different durations. When late 2-cells were incubated with 5 μM fluoxetine for 6 h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetinemore » (5 μM) over 24 h showed a reduction in blastocyst formation. The addition of fluoxetine (5 μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K{sup +} channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ∼ 30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Highlights: ► Short-term exposure of 2-cells to fluoxetine enhances mouse blastocyst formation. ► The enhancive effect of fluoxetine is resulted from Ca

  12. Prenatal cocaine effects on brain structure in early infancy.

    PubMed

    Grewen, Karen; Burchinal, Margaret; Vachet, Clement; Gouttard, Sylvain; Gilmore, John H; Lin, Weili; Johns, Josephine; Elam, Mala; Gerig, Guido

    2014-11-01

    Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Adsorption of cellular peptides of Microcystis aeruginosa and two herbicides onto activated carbon: effect of surface charge and interactions.

    PubMed

    Hnatukova, Petra; Kopecka, Ivana; Pivokonsky, Martin

    2011-05-01

    In this research, the adsorption of two herbicides, alachlor (ALA) and terbuthylazine (TBA), on granular activated carbon (GAC) in the presence of well-characterized peptide fraction of cellular organic matter (COM) produced by cyanobacterium Microcystis aeruginosa was studied. Two commercially available GACs were characterized using nitrogen gas adsorption and surface charge titrations. The COM peptides of molecular weight (MW) < 10 kDa were isolated and characterized using MW fractionation technique and high-performance size exclusion chromatography (HPSEC). The effect of surface charge on the adsorption of COM peptides was studied by means of equilibrium adsorption experiments at pH 5 and pH 8.5. Electrostatic interactions and hydrogen bonding proved to be important mechanisms of COM peptides adsorption. The adsorption of ALA and TBA on granular activated carbon preloaded with COM peptides was influenced by solution pH. The reduction in adsorption was significantly greater at pH 5 compared to pH 8.5, which corresponded to the increased adsorption of COM peptides at pH 5. The majority of the competition between COM peptides and both herbicides was attributed to low molecular weight COM peptides with MW of 700, 900, 1300 and 1700 Da. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Characterization of cellular protective effects of ATP13A2/PARK9 expression and alterations resulting from pathogenic mutants.

    PubMed

    Covy, Jason P; Waxman, Elisa A; Giasson, Benoit I

    2012-12-01

    Mutations in ATP13A2, which encodes a lysosomal P-type ATPase of unknown function, cause an autosomal recessive parkinsonian syndrome. With mammalian cells, we show that ATP13A2 expression protects against manganese and nickel toxicity, in addition to proteasomal, mitochondrial, and oxidative stress. Consistent with a recessive mode of inheritance of gene defects, disease-causing mutations F182L and G504R are prone to misfolding and do not protect against manganese and nickel toxicity because they are unstable as a result of degradation via the endoplasmic reticulum-associated degradation (ERAD)-proteasome system. The protective effects of ATP13A2 expression are not due to inhibition of apoptotic pathways or a reduction in typical stress pathways, insofar as these pathways are still activated in challenged ATP13A2-expressing cells; however, these cells display a dramatic reduction in the accumulation of oxidized and damaged proteins. These data indicate that, contrary to a previous suggestion, ATP13A2 is unlikely to convey cellular resilience simply by acting as a lysosomal manganese transporter. Consistent with the recent identification of an ATP13A2 recessive mutation in Tibetan terriers that develop neurodegeneration with neuronal ceroid lipofucinoses, our data suggest that ATP13A2 may function to import a cofactor required for the function of a lysosome enzyme(s). Copyright © 2012 Wiley Periodicals, Inc.

  15. A tripeptide isolated from Bothrops atrox venom has neuroprotective and neurotrophic effects on a cellular model of Parkinson's disease.

    PubMed

    Martins, N M; Santos, N A G; Sartim, M A; Cintra, A C O; Sampaio, S V; Santos, A C

    2015-06-25

    Parkinson's disease (PD) is the second most common neurodegenerative disorder; however, there is no treatment able to prevent the loss of dopaminergic neurons or its consequences. Trophic factors such as NGF and BDNF has positive effects on different disorders of the brain, including neurodegeneration. Additionally, studies have suggested the use of venom peptides as a therapeutic strategy for neurological disorders. Therefore, in the present study, we investigated the neuroprotective activity of a peptide isolated from Bothrops atrox venom and its trophic ability by using a cellular model of dopaminergic neurotoxicity induced by 1-methyl-4-phenylpyridinium (MPP(+)) in PC12 cells. We showed that it decreased the activities of the apoptotic proteases caspase-9 (mitochondrial) and caspase-3 (executor) and increased cell viability and proliferation in this model. Additionally, it increased neuritogenesis in non-treated PC12 cells (neuronal model) as well as in PC12 cells treated with the dopaminergic neurotoxin. The amino acid sequence of the peptide was identified as Glutamic acid-Valine-Tryptophan (Glu-Val-Trp). These findings suggest that this tripeptide has the potential to protect against the dopaminergic neurons loss and that trophic stimulation of neuroplasticity might be involved in its mechanism of neuroprotection. Copyright © 2015. Published by Elsevier Ireland Ltd.

  16. Effects of Graphene Oxide and Oxidized Carbon Nanotubes on the Cellular Division, Microstructure, Uptake, Oxidative Stress, and Metabolic Profiles.

    PubMed

    Hu, Xiangang; Ouyang, Shaohu; Mu, Li; An, Jing; Zhou, Qixing

    2015-09-15

    Nanomaterial oxides are common formations of nanomaterials in the natural environment. Herein, the nanotoxicology of typical graphene oxide (GO) and carboxyl single-walled carbon nanotubes (C-SWCNT) was compared. The results showed that cell division of Chlorella vulgaris was promoted at 24 h and then inhibited at 96 h after nanomaterial exposure. At 96 h, GO and C-SWCNT inhibited the rates of cell division by 0.08-15% and 0.8-28.3%, respectively. Both GO and C-SWCNT covered the cell surface, but the uptake percentage of C-SWCNT was 2-fold higher than that of GO. C-SWCNT induced stronger plasmolysis and mitochondrial membrane potential loss and decreased the cell viability to a greater extent than GO. Moreover, C-SWCNT-exposed cells exhibited more starch grains and lysosome formation and higher reactive oxygen species (ROS) levels than GO-exposed cells. Metabolomics analysis revealed significant differences in the metabolic profiles among the control, C-SWCNT and GO groups. The metabolisms of alkanes, lysine, octadecadienoic acid and valine was associated with ROS and could be considered as new biomarkers of ROS. The nanotoxicological mechanisms involved the inhibition of fatty acid, amino acid and small molecule acid metabolisms. These findings provide new insights into the effects of GO and C-SWCNT on cellular responses.

  17. Effects of temperature, CO2/O2 concentrations and light intensity on cellular multiplication of microalgae, Euglena gracilis

    NASA Technical Reports Server (NTRS)

    Kitaya, Y.; Azuma, H.; Kiyota, M.

    2005-01-01

    Microalgae culture is likely to play an important role in aquatic food production modules in bioregenerative systems for producing feeds for fish, converting CO2 to O2 and remedying water quality as well as aquatic higher plants. In the present study, the effects of culture conditions on the cellular multiplication of microalgae, Euglena gracilis, was investigated as a fundamental study to determine the optimum culture conditions for microalgae production in aquatic food production modules including both microalgae culture and fish culture systems. E. gracilis was cultured under conditions with five levels of temperatures (25-33 degrees C), three levels of CO2 concentrations (2-6%), five levels of O2 concentrations (10-30%), and six levels of photosynthetic photon flux (20-200 micromoles m-2 s-1). The number of Euglena cells in a certain volume of solution was monitored with a microscope under each environmental condition. The multiplication rate of the cells was highest at temperatures of 27-31 degrees C, CO2 concentration of 4%, O2 concentration of 20% and photosynthetic photon flux of about 100 micromoles m-2 s-1. The results demonstrate that E. gracilis could efficiently produce biomass and convert CO2 to O2 under relatively low light intensities in aquatic food production modules. c2005 Published by Elsevier Ltd on behalf of COSPAR.

  18. Effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells.

    PubMed

    Cai, Guoping; Lai, Binbin; Hong, Huaxing; Lin, Peng; Chen, Weifu; Zhu, Zhong; Chen, Haixiao

    2017-07-01

    Cryopreservation is widely used in regenerative medicine for tissue preservation. In the present study, the effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells (HUVECs) were investigated. After 0, 4, 8, 12 or 24 weeks of cryopreservation in liquid nitrogen, the HUVECs were thawed. The excretory functions markers (endothelin‑1, prostaglandin E1, von Willebrand factor and nitric oxide) of HUVECs were measured by ELISA assay. The expression of intercellular adhesion molecule‑1 (ICAM‑1) in HUVECs was analyzed using flow cytometry. An angiogenesis assay was used to determine the angiogeneic capabilities of the thawed HUVECs. The results demonstrated that cryopreserved/thawed and recultivated HUVECs were unsuitable for tissue‑engineered microvascular construction. Specifically, the excretory function of the cells was significantly decreased in the post‑cryopreserved HUVECs at 24 weeks. In addition, the level of ICAM‑1 in HUVECs was significantly upregulated from the fourth week of cryopreservation. Furthermore, the tube‑like structure‑forming potential was weakened with increasing cryopreservation duration, and the numbers of lumen and the length of the pipeline were decreased in the thawed HUVECs, in a time‑dependent manner. In conclusion, the results of the present study revealed that prolonged cryopreservation may lead to HUVEC dysfunction and did not create stable cell lines for tissue‑engineered microvascular construction.

  19. An effective approach of lesion segmentation within the breast ultrasound image based on the cellular automata principle.

    PubMed

    Liu, Yan; Cheng, H D; Huang, Jianhua; Zhang, Yingtao; Tang, Xianglong

    2012-10-01

    In this paper, a novel lesion segmentation within breast ultrasound (BUS) image based on the cellular automata principle is proposed. Its energy transition function is formulated based on global image information difference and local image information difference using different energy transfer strategies. First, an energy decrease strategy is used for modeling the spatial relation information of pixels. For modeling global image information difference, a seed information comparison function is developed using an energy preserve strategy. Then, a texture information comparison function is proposed for considering local image difference in different regions, which is helpful for handling blurry boundaries. Moreover, two neighborhood systems (von Neumann and Moore neighborhood systems) are integrated as the evolution environment, and a similarity-based criterion is used for suppressing noise and reducing computation complexity. The proposed method was applied to 205 clinical BUS images for studying its characteristic and functionality, and several overlapping area error metrics and statistical evaluation methods are utilized for evaluating its performance. The experimental results demonstrate that the proposed method can handle BUS images with blurry boundaries and low contrast well and can segment breast lesions accurately and effectively.

  20. Development of a cell culture surface conversion technique using alginate thin film for evaluating effect upon cellular differentiation

    SciTech Connect

    Nakashima, Y., E-mail: yuta-n@mech.kumamoto-u.ac.jp; Graduate School of Science and Engineering, Yamaguchi University, 2-16-1 Tokiwadai, Ube 755-8611; Tsusu, K.

    2014-06-15

    Here, we sought to develop a cell culture surface conversion technique that would not damage living cells. An alginate thin film, formed on a glass plate by spin coating of sodium alginate solution and dipping into calcium chloride solution, was used to inhibit adhesion of cells. The film could be removed by ethylenediaminetetraacetate (EDTA) at any time during cell culture, permitting observation of cellular responses to conversion of the culture surface in real time. Additionally, we demonstrated the validity of the alginate thin film coating method and the performance of the film. The thickness of the alginate thin film wasmore » controlled by varying the rotation speed during spin coating. Moreover, the alginate thin film completely inhibited the adhesion of cultured cells to the culture surface, irrespective of the thickness of the film. When the alginate thin film was removed from the culture surface by EDTA, the cultured cells adhered to the culture surface, and their morphology changed. Finally, we achieved effective differentiation of C2C12 myoblasts into myotube cells by cell culture on the convertible culture surface, demonstrating the utility of our novel technique.« less

  1. Cellular Phenotype-Dependent and -Independent Effects of Vitamin C on the Renewal and Gene Expression of Mouse Embryonic Fibroblasts

    PubMed Central

    Kuo, Shiu-Ming; Burl, Lana R.; Hu, Zihua

    2012-01-01

    Vitamin C has been shown to delay the cellular senescence and was considered a candidate for chemoprevention and cancer therapy. To understand the reported contrasting roles of vitamin C: growth-promoting in the primary cells and growth-inhibiting in cancer cells, primary mouse embryonic fibroblasts (MEF) and their isogenic spontaneously immortalized fibroblasts with unlimited cell division potential were used as the model pair. We used microarray gene expression profiling to show that the immortalized MEF possess human cancer gene expression fingerprints including a pattern of up-regulation of inflammatory response-related genes. Using the MEF model, we found that a physiological treatment level of vitamin C (10−5 M), but not other unrelated antioxidants, enhanced cell growth. The growth-promoting effect was associated with a pattern of enhanced expression of cell cycle- and cell division-related genes in both primary and immortalized cells. In the immortalized MEF, physiological treatment levels of vitamin C also enhanced the expression of immortalization-associated genes including a down-regulation of genes in the extracellular matrix functional category. In contrast, confocal immunofluorescence imaging of the primary MEF suggested an increase in collagen IV protein upon vitamin C treatment. Similar to the cancer cells, the growth-inhibitory effect of the redox-active form of vitamin C was preferentially observed in immortalized MEF. All effects of vitamin C required its intracellular presence since the transporter-deficient SVCT2−/− MEF did not respond to vitamin C. SVCT2−/− MEF divided and became immortalized readily indicating little dependence on vitamin C for the cell division. Immortalized SVCT2−/− MEF required higher concentration of vitamin C for the growth inhibition compared to the immortalized wildtype MEF suggesting an intracellular vitamin C toxicity. The relevance of our observation in aging and human cancer prevention was discussed

  2. Effects of TORC1 Inhibition during the Early and Established Phases of Polycystic Kidney Disease

    PubMed Central

    Ta, Michelle H. T.; Schwensen, Kristina G.; Foster, Sheryl; Korgaonkar, Mayuresh; Ozimek-Kulik, Justyna E.; Phillips, Jacqueline K.; Peduto, Anthony; Rangan, Gopala K.

    2016-01-01

    The disease-modifying effects of target of rapamycin complex 1 (TORC1) inhibitors during different stages of polycystic kidney disease (PKD) are not well defined. In this study, male Lewis Polycystic Kidney Disease (LPK) rats (a genetic ortholog of human NPHP9, phenotypically characterised by diffuse distal nephron cystic growth) and Lewis controls received either vehicle (V) or sirolimus (S, 0.2 mg/kg by intraperitoneal injection 5 days per week) during the early (postnatal weeks 3 to 10) or late stages of disease (weeks 10 to 20). In early-stage disease, sirolimus reduced kidney enlargement (by 63%), slowed the rate of increase in total kidney volume (TKV) in serial MRI by 78.2% (LPK+V: 132.3±59.7 vs. LPK+S: 28.8±12.0% per week) but only partly reduced the percentage renal cyst area (by 19%) and did not affect the decline in endogenous creatinine clearance (CrCl) in LPK rats. In late-stage disease, sirolimus reduced kidney enlargement (by 22%) and the rate of increase in TKV by 71.8% (LPK+V: 13.1±6.6 vs. LPK+S: 3.7±3.7% per week) but the percentage renal cyst area was unaltered, and the CrCl only marginally better. Sirolimus reduced renal TORC1 activation but not TORC2, NF-κB DNA binding activity, CCL2 or TNFα expression, and abnormalities in cilia ultrastructure, hypertension and cardiac disease were also not improved. Thus, the relative treatment efficacy of TORC1 inhibition on kidney enlargement was consistent at all disease stages, but the absolute effect was determined by the timing of drug initiation. Furthermore, cystic microarchitecture, renal function and cardiac disease remain abnormal with TORC1 inhibition, indicating that additional approaches to normalise cellular dedifferentiation, inflammation and hypertension are required to completely arrest the progression of PKDs. PMID:27723777

  3. Comparison of effects of inhibitors of viral and cellular protein kinases on human cytomegalovirus disruption of nuclear lamina and nuclear egress.

    PubMed

    Sharma, Mayuri; Coen, Donald M

    2014-09-01

    Human cytomegalovirus (HCMV) kinase UL97 is required for efficient nuclear lamina disruption during nuclear egress. However, cellular protein kinase C (PKC) has been implicated in this process in other systems. Comparing the effects of UL97 and cellular kinase inhibitors on HCMV nuclear egress confirms a role for UL97 in lamina disruption and nuclear egress. A pan-PKC inhibitor did not affect lamina disruption but did reduce the number of cytoplasmic capsids more than the number of nuclear capsids. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  4. Studying the Effects of Early Experiences on Women's Career Achievement.

    ERIC Educational Resources Information Center

    Lykes, M. Brinton; Stewart, Abigail J.

    Virtually all psychological theories assume that early life experiences have an impact on later life choices. However, increasing doubts have been expressed about the universality and permanence of the relationship between women's work and family lives. To explore how early family experiences and early adult decisions affect women's later career…

  5. The Effects of Breastfeeding Exclusivity on Early Childhood Outcomes

    PubMed Central

    Foster, E. Michael

    2014-01-01

    Objectives. We examined the relationship between breastfeeding exclusivity and duration and children’s health and cognitive outcomes at ages 2 and 4 years. Methods. We used the Early Childhood Longitudinal Study—Birth Cohort, a nationally representative sample of 10 700 children born in the United States in 2001. Parent interviews and child assessments were conducted in measurement waves at 9 months, 2 years, 4 years, and in kindergarten, with the focus on ages 2 and 4 years. We employed propensity scores as a means of adjusting for confounding involving observed characteristics. Results. Outcome analyses using propensity scores showed some small effects of breastfeeding on key outcomes at age 4 years but not at age 2 years. Effects appeared to be concentrated in reading and cognitive outcomes. Overall, we found no consistent evidence for dosage effects of breastfeeding exclusivity. Our sensitivity analyses revealed that a small amount of unobserved confounding could be responsible for the resulting benefits. Conclusions. Our study revealed little or no effect of breastfeeding exclusivity and duration on key child outcomes. PMID:24354838

  6. Longitudinal Effects on Early Adolescent Language: A Twin Study

    PubMed Central

    DeThorne, Laura Segebart; Smith, Jamie Mahurin; Betancourt, Mariana Aparicio; Petrill, Stephen A.

    2016-01-01

    Purpose We evaluated genetic and environmental contributions to individual differences in language skills during early adolescence, measured by both language sampling and standardized tests, and examined the extent to which these genetic and environmental effects are stable across time. Method We used structural equation modeling on latent factors to estimate additive genetic, shared environmental, and nonshared environmental effects on variance in standardized language skills (i.e., Formal Language) and productive language-sample measures (i.e., Productive Language) in a sample of 527 twins across 3 time points (mean ages 10–12 years). Results Individual differences in the Formal Language factor were influenced primarily by genetic factors at each age, whereas individual differences in the Productive Language factor were primarily due to nonshared environmental influences. For the Formal Language factor, the stability of genetic effects was high across all 3 time points. For the Productive Language factor, nonshared environmental effects showed low but statistically significant stability across adjacent time points. Conclusions The etiology of language outcomes may differ substantially depending on assessment context. In addition, the potential mechanisms for nonshared environmental influences on language development warrant further investigation. PMID:27732720

  7. Effect of secondary metabolite of Actinidia deliciosa on the biofilm and extra-cellular matrix components of Acinetobacter baumannii.

    PubMed

    Tiwari, Vishvanath; Tiwari, Deepika; Patel, Varsha; Tiwari, Monalisa

    2017-09-01

    Acinetobacter baumannii, opportunistic nosocomial pathogen, increases gradually in the clinical setup. The high level of resistance mechanisms acquired by these bacteria makes their eradication difficult and biofilm formation is one of them. Biofilm comprises of closely packed bacterial population crowded together by extra-cellular matrix (ECM). ECM contains bacterial secreted polymers such as exopolysaccharides (EPS), proteins and extracellular-DNA (e-DNA) and rarely amyloidogenic proteins. Biofilm offers protection of underlying bacterial population against chemotherapeutic agents and host immune system. Therefore, present efforts are focused to find a novel therapeutic that targets biofilm-associated infections. Plants are used as a natural therapeutic for numerous ailments. In order to find an alternative of the available antibacterial drugs, we have focused on the natural herbal active compounds. In this study, we have extracted active compounds from various medicinal plants and screened its anti-biofilm activity against carbapenem resistant strain of A. baumannii. Results showed that polar extract of kiwi (Actinidia deliciosa) and clove (Syzygium aromaticum) exhibit effective anti-biofilm activity. These two plants were also used for their phytochemical screening and TLC profiling to find out the constituting secondary metabolites. Actinidia deliciosa extract contains an alkaloid (sanquinarine) as well as a flavonoid (hydroxyflavone). Anti-biofilm effect of this extract on the ECM of A. baumannii showed that it reduces EPS, protein and eDNA contents in the ECM. Proteins of ECM have also shown to form amyloid like structure, which was evident from its interaction with the Congo Red. CFU counting after Actinidia deliciosa extract treatment also supported the results. Therefore, it can be concluded that polar extract of A. deliciosa can be used to find suitable alternative therapeutic to control biofilm formation by carbapenem resistant strain of

  8. Effects of Selected Egyptian Honeys on the Cellular Ultrastructure and the Gene Expression Profile of Escherichia coli.

    PubMed

    Wasfi, Reham; Elkhatib, Walid F; Khairalla, Ahmed S

    2016-01-01

    The purpose of this study was to: (i) evaluate the antibacterial activities of three Egyptian honeys collected from different floral sources (namely, citrus, clover, and marjoram) against Escherichia coli; (ii) investigate the effects of these honeys on bacterial ultrastructure; and (iii) assess the anti-virulence potential of these honeys, by examining their impacts on the expression of eight selected genes (involved in biofilm formation, quorum sensing, and stress survival) in the test organism. The minimum inhibitory concentration (MIC) of the honey samples against E. coli ATCC 8739 were assessed by the broth microdilution assay in the presence and absence of catalase enzyme. Impacts of the honeys on the cellular ultrastructure and the expression profiles of the selected genes of E. coli were examined using transmission electron microscopy (TEM) and quantitative real-time polymerase chain reaction (qPCR) analysis, respectively. The susceptibility tests showed promising antibacterial activities of all the tested honeys against E. coli. This was supported by the TEM observations, which revealed "ghost" cells lacking DNA, in addition to cells with increased vacuoles, and/or with irregular shrunken cytoplasm. Among the tested honeys, marjoram exhibited the highest total antibacterial activity and the highest levels of peroxide-dependent activity. The qPCR analysis showed that all honey-treated cells share a similar overall pattern of gene expression, with a trend toward reduced expression of the virulence genes of interest. Our results indicate that some varieties of the Egyptian honey have the potential to be effective inhibitor and virulence modulator of E. coli via multiple molecular targets.

  9. Effects of Selected Egyptian Honeys on the Cellular Ultrastructure and the Gene Expression Profile of Escherichia coli

    PubMed Central

    Elkhatib, Walid F.

    2016-01-01

    The purpose of this study was to: (i) evaluate the antibacterial activities of three Egyptian honeys collected from different floral sources (namely, citrus, clover, and marjoram) against Escherichia coli; (ii) investigate the effects of these honeys on bacterial ultrastructure; and (iii) assess the anti-virulence potential of these honeys, by examining their impacts on the expression of eight selected genes (involved in biofilm formation, quorum sensing, and stress survival) in the test organism. The minimum inhibitory concentration (MIC) of the honey samples against E. coli ATCC 8739 were assessed by the broth microdilution assay in the presence and absence of catalase enzyme. Impacts of the honeys on the cellular ultrastructure and the expression profiles of the selected genes of E. coli were examined using transmission electron microscopy (TEM) and quantitative real-time polymerase chain reaction (qPCR) analysis, respectively. The susceptibility tests showed promising antibacterial activities of all the tested honeys against E. coli. This was supported by the TEM observations, which revealed “ghost” cells lacking DNA, in addition to cells with increased vacuoles, and/or with irregular shrunken cytoplasm. Among the tested honeys, marjoram exhibited the highest total antibacterial activity and the highest levels of peroxide-dependent activity. The qPCR analysis showed that all honey-treated cells share a similar overall pattern of gene expression, with a trend toward reduced expression of the virulence genes of interest. Our results indicate that some varieties of the Egyptian honey have the potential to be effective inhibitor and virulence modulator of E. coli via multiple molecular targets. PMID:26954570

  10. The cellular and molecular effects of the androgen receptor agonist, Cl-4AS-1, on breast cancer cells.

    PubMed

    Ahram, Mamoun; Mustafa, Ebtihal; Abu Hammad, Shatha; Alhudhud, Mariam; Bawadi, Randa; Tahtamouni, Lubna; Khatib, Faisal; Zihlif, Malek

    2018-03-26

    The androgen receptor (AR) has attracted attention in the treatment of breast cancer. Due to the undesirable side effects of AR agonists, attempts have been undertaken to develop selective AR modulators. One of these compounds is Cl-4AS-1. This study examined this compound more closely at the cellular and molecular levels. Three different breast cancer cell lines were utilized, namely the luminal MCF-7 cells, the molecular apocrine MDA-MB-453 cells, and the triple negative, basal MDA-MB-231 cells. High and significant concordance between dihydrotestosterone (DHT) and Cl-4AS-1 in regulation of gene expression in MDA-MB-453 cells was found. However, some differences were noted including the expression of AR, which was upregulated by DHT, but not Cl-4AS-1. In addition, both DHT and Cl-4AS-1 caused a similar morphological change and reorganization of the actin structure of MDA-MB-453 cells into a mesenchymal phenotype. Treatment of cells with DHT resulted in induction of proliferation of MCF-7 and MDA-MB-453 cells, but no effect was observed on the growth of MDA-MB-231 cells. On the other hand, increasing doses of Cl-4AS-1 resulted in a dose-dependent inhibition on the growth of the three cell lines. This inhibition was a result of induction of apoptosis whereby Cl-4AS-1 caused a block in entry of cells into the S-phase followed by DNA degradation. These results indicate that although Cl-4AS-1 has characteristics of classical AR agonist, it has dissimilar properties that may make it useful in treating breast cancer.

  11. Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells: Characterization of Cellular Responses and Identification of Molecular Determinants

    PubMed Central

    Rodrigues, Valérie; Fernandez, Bernard; Vercoutere, Arthur; Chamayou, Léo; Andersen, Alexandre; Vigy, Oana; Demettre, Edith; Seveno, Martial; Aprelon, Rosalie; Giraud-Girard, Ken; Stachurski, Frédéric; Loire, Etienne; Vachiéry, Nathalie; Holzmuller, Philippe

    2018-01-01

    The tropical bont tick, Amblyomma variegatum, is a tick species of veterinary importance and is considered as one of major pest of ruminants in Africa and in the Caribbean. It causes direct skin lesions, transmits heartwater, and reactivates bovine dermatophilosis. Tick saliva is reported to affect overall host responses through immunomodulatory and anti-inflammatory molecules, among other bioactive molecules. The general objective of this study was to better understand the role of saliva in interaction between the Amblyomma tick and the host using cellular biology approaches and proteomics, and to discuss its impact on disease transmission and/or activation. We first focused on the immuno-modulating effects of semi-fed A. variegatum female saliva on bovine peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages in vitro. We analyzed its immuno-suppressive properties by measuring the effect of saliva on PBMC proliferation, and observed a significant decrease in ConA-stimulated PBMC lymphoproliferation. We then studied the effect of saliva on bovine macrophages using flow cytometry to analyze the expression of MHC-II and co-stimulation molecules (CD40, CD80, and CD86) and by measuring the production of nitric oxide (NO) and pro- or anti-inflammatory cytokines. We observed a significant decrease in the expression of MHC-II, CD40, and CD80 molecules, associated with decreased levels of IL-12-p40 and TNF-α and increased level of IL-10, which could explain the saliva-induced modulation of NO. To elucidate these immunomodulatory effects, crude saliva proteins were analyzed using proteomics with an Orbitrap Elite mass spectrometer. Among the 336 proteins identified in A. variegatum saliva, we evidenced bioactive molecules exhibiting anti-inflammatory, immuno-modulatory, and anti-oxidant properties (e.g., serpins, phospholipases A2, heme lipoprotein). We also characterized an intriguing ubiquitination complex that could be involved in saliva

  12. The effects of perception of risk and importance of answering and initiating a cellular phone call while driving.

    PubMed

    Nelson, Erik; Atchley, Paul; Little, Todd D

    2009-05-01

    Recent data suggest that laws banning cellular phone use while driving may not change use patterns, especially among young drivers with high rates of mobile phone adoption. We examined reasons younger drivers choose or do not choose to talk on a phone while driving among a sample of young drivers (n=276) with very high ownership of cellular phones (over 99%) and a very high use of cellular phones while driving (100% for those that were primary operators of an automobile). Respondents were surveyed for patterns of use, types of call, perceived risk, and motivations for use. The data were analyzed using structural equation modeling (SEM) to explore the relationships between perceived risk of the behavior, emotionality of the call, perceived importance of the call, and how often calls were initiated versus answered. The model suggests that even though people believe that talking on a cellular phone while driving is dangerous, they will tend to initiate a cellular conversation if they believe that the call is important.

  13. Cost-effectiveness model for prevention of early childhood caries.

    PubMed

    Ramos-Gomez, F J; Shepard, D S

    1999-07-01

    This study presents and illustrates a model that determines the cost-effectiveness of three successively more complete levels of preventive intervention (minimal, intermediate, and comprehensive) in treating dental caries in disadvantaged children up to 6 years of age. Using existing data on the costs of early childhood caries (ECC), the authors estimated the probable cost-effectiveness of each of the three preventive intervention levels by comparing treatment costs to prevention costs as applied to a typical low-income California child for five years. They found that, in general, prevention becomes cost-saving if at least 59 percent of carious lesions receive restorative treatment. Assuming an average restoration cost of $112 per surface, the model predicts cost savings of $66 to $73 in preventing a one-surface, carious lesion. Thus, all three levels of preventive intervention should be relatively cost-effective. Comprehensive intervention would provide the greatest oral health benefit; however, because more children would receive reparative care, overall program costs would rise even as per-child treatment costs decline.

  14. Early universe cosmology, effective supergravity, and invariants of algebraic forms

    NASA Astrophysics Data System (ADS)

    Sinha, Kuver

    2015-09-01

    The presence of light scalars can have profound effects on early universe cosmology, influencing its thermal history as well as paradigms like inflation and baryogenesis. Effective supergravity provides a framework to make quantifiable, model-independent studies of these effects. The Riemannian curvature of the Kähler manifold spanned by scalars belonging to chiral superfields, evaluated along supersymmetry breaking directions, provides an order parameter (in the sense that it must necessarily take certain values) for phenomena as diverse as slow roll modular inflation, nonthermal cosmological histories, and the viability of Affleck-Dine baryogenesis. Within certain classes of UV completions, the order parameter for theories with n scalar moduli is conjectured to be related to invariants of n -ary cubic forms (for example, for models with three moduli, the order parameter is given by a function on the ring of invariants spanned by the Aronhold invariants). Within these completions, and under the caveats spelled out, this may provide an avenue to obtain necessary conditions for the above phenomena that are in principle calculable given nothing but the intersection numbers of a Calabi-Yau compactification geometry. As an additional result, abstract relations between holomorphic sectional and bisectional curvatures are utilized to constrain Affleck-Dine baryogenesis on a wide class of Kähler geometries.

  15. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol.

    PubMed

    Hodis, Howard N; Mack, Wendy J; Henderson, Victor W; Shoupe, Donna; Budoff, Matthew J; Hwang-Levine, Juliana; Li, Yanjie; Feng, Mei; Dustin, Laurie; Kono, Naoko; Stanczyk, Frank Z; Selzer, Robert H; Azen, Stanley P

    2016-03-31

    Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested. A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen. After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum. Oral estradiol

  16. Effects of 5-fluorouracil in nuclear and cellular morphology, proliferation, cell cycle, apoptosis, cytoskeletal and caveolar distribution in primary cultures of smooth muscle cells.

    PubMed

    Filgueiras, Marcelo de Carvalho; Morrot, Alexandre; Soares, Pedro Marcos Gomes; Costa, Manoel Luis; Mermelstein, Cláudia

    2013-01-01

    Colon cancer is one of the most prevalent types of cancer in the world and is one of the leading causes of cancer death. The anti-metabolite 5- fluorouracil (5-FU) is widely used in the treatment of patients with colon cancer and other cancer types. 5-FU-based chemotherapy has been shown to be very efficient in the improvement of overall survival of the patients and for the eradication of the disease. Unfortunately, common side effects of 5-FU include severe alterations in the motility of the gastrointestinal tissues. Nevertheless, the molecular and cellular effects of 5-FU in smooth muscle cells are poorly understood. Primary smooth muscle cell cultures are an important tool for studies of the biological consequences of 5-FU at the cellular level. The avian gizzard is one of the most robust organs of smooth muscle cells. Here we studied the molecular and cellular effects of the chemotherapic drug 5-FU in a primary culture of chick gizzard smooth muscle cells. We found that treatment of smooth muscle cells with 5-FU inhibits cell proliferation by the arrest of cells in the G1 phase of cell cycle and induce apoptosis. 5-FU induced a decrease in the percentage of histone H3-positive cells. Treatment of cells with 5-FU induced changes in cellular and nuclear morphology, a decrease in the number of stress fibers and a major decrease in the number of caveolin-3 positive cells. Our results suggest that the disorganization of the actin cytoskeleton and the reduction of caveolin-3 expression could explain the alterations in contractility observed in patients treated with 5-FU. These findings might have an impact in the understanding of the cellular effects of 5-FU in smooth muscle tissues and might help the improvement of new therapeutic protocols for the treatment of colon cancer.

  17. Effects of 5-Fluorouracil in Nuclear and Cellular Morphology, Proliferation, Cell Cycle, Apoptosis, Cytoskeletal and Caveolar Distribution in Primary Cultures of Smooth Muscle Cells

    PubMed Central

    Filgueiras, Marcelo de Carvalho; Morrot, Alexandre; Soares, Pedro Marcos Gomes; Costa, Manoel Luis; Mermelstein, Cláudia

    2013-01-01

    Colon cancer is one of the most prevalent types of cancer in the world and is one of the leading causes of cancer death. The anti-metabolite 5- fluorouracil (5-FU) is widely used in the treatment of patients with colon cancer and other cancer types. 5-FU-based chemotherapy has been shown to be very efficient in the improvement of overall survival of the patients and for the eradication of the disease. Unfortunately, common side effects of 5-FU include severe alterations in the motility of the gastrointestinal tissues. Nevertheless, the molecular and cellular effects of 5-FU in smooth muscle cells are poorly understood. Primary smooth muscle cell cultures are an important tool for studies of the biological consequences of 5-FU at the cellular level. The avian gizzard is one of the most robust organs of smooth muscle cells. Here we studied the molecular and cellular effects of the chemotherapic drug 5-FU in a primary culture of chick gizzard smooth muscle cells. We found that treatment of smooth muscle cells with 5-FU inhibits cell proliferation by the arrest of cells in the G1 phase of cell cycle and induce apoptosis. 5-FU induced a decrease in the percentage of histone H3-positive cells. Treatment of cells with 5-FU induced changes in cellular and nuclear morphology, a decrease in the number of stress fibers and a major decrease in the number of caveolin-3 positive cells. Our results suggest that the disorganization of the actin cytoskeleton and the reduction of caveolin-3 expression could explain the alterations in contractility observed in patients treated with 5-FU. These findings might have an impact in the understanding of the cellular effects of 5-FU in smooth muscle tissues and might help the improvement of new therapeutic protocols for the treatment of colon cancer. PMID:23646193

  18. Telomere dynamics in wild brown trout: effects of compensatory growth and early growth investment.

    PubMed

    Näslund, Joacim; Pauliny, Angela; Blomqvist, Donald; Johnsson, Jörgen I

    2015-04-01

    After a period of food deprivation, animals often respond with a period of faster than normal growth. Such responses have been suggested to result in decreased chromosomal maintenance, which in turn may affect the future fitness of an individual. Here, we present a field experiment in which a food deprivation period of 24 days was enforced on fish from a natural population of juvenile brown trout (Salmo trutta) at the start of the high-growth season in spring. The growth of the food-deprived fish and a non-deprived control group was then monitored in the wild during 1 year. Fin tissue samples were taken at the start of the experiment and 1 year after food deprivation to monitor the telomere dynamics, using reduced telomere length as an indicator of maintenance cost. The food-deprived fish showed partial compensatory growth in both mass and length relative to the control group. However, we found no treatment effects on telomere dynamics, suggesting that growth-compensating brown trout juveniles are able to maintain their telomeres during their second year in the stream. However, body size at the start of the experiment, reflecting growth rate during their first year of life, was negatively correlated with change in telomere length over the following year. This result raises the possibility that rapid growth early in life induces delayed costs in cellular maintenance.

  19. Cellular re- and de-programming by microenvironmental memory: why short TGF-β1 pulses can have long effects

    PubMed Central

    2013-01-01

    Background Fibrosis poses a substantial setback in regenerative medicine. Histopathologically, fibrosis is an excessive accumulation of collagen affected by myofibroblasts and this can occur in any tissue that is exposed to chronic injury or insult. Transforming growth factor (TGF)-β1, a crucial mediator of fibrosis, drives differentiation of fibroblasts into myofibroblasts. These cells exhibit α-smooth muscle actin (α-SMA) and synthesize high amounts of collagen I, the major extracellular matrix (ECM) component of fibrosis. While hormones stimulate cells in a pulsatile manner, little is known about cellular response kinetics upon growth factor impact. We therefore studied the effects of short TGF-β1 pulses in terms of the induction and maintenance of the myofibroblast phenotype. Results Twenty-four hours after a single 30 min TGF-β1 pulse, transcription of fibrogenic genes was upregulated, but subsided 7 days later. In parallel, collagen I secretion rate and α-SMA presence were elevated for 7 days. A second pulse 24 h later extended the duration of effects to 14 days. We could not establish epigenetic changes on fibrogenic target genes to explain the long-lasting effects. However, ECM deposited under singly pulsed TGF-β1 was able to induce myofibroblast features in previously untreated fibroblasts. Dependent on the age of the ECM (1 day versus 7 days’ formation time), this property was diminished. Vice versa, myofibroblasts were cultured on fibroblast ECM and cells observed to express reduced (in comparison with myofibroblasts) levels of collagen I. Conclusions We demonstrated that short TGF-β1 pulses can exert long-lasting effects on fibroblasts by changing their microenvironment, thus leaving an imprint and creating a reciprocal feed-back loop. Therefore, the ECM might act as mid-term memory for pathobiochemical events. We would expect this microenvironmental memory to be dependent on matrix turnover and, as such, to be erasable. Our findings

  20. Effects of chronic copper exposure during early life in rhesus monkeys.

    PubMed

    Araya, Magdalena; Kelleher, Shannon L; Arredondo, Miguel A; Sierralta, Walter; Vial, María Teresa; Uauy, Ricardo; Lönnerdal, Bo

    2005-05-01

    Whether infants regulate copper absorption and the potential effects of excess copper in early life remain poorly defined. The objective of the study was to assess copper retention, liver copper content, and liver function in infant rhesus monkeys fed infant formula containing 6.6 mg Cu/L. From birth to 5 mo of age, infant rhesus monkeys were fed formula that was supplemented with copper (0.6 mg Cu/L; n = 5) or not supplemented (n = 4). In all animals, weight and crown-rump length (by anthropometry), hemoglobin, hematocrit, plasma ceruloplasmin activity, and zinc and copper concentrations were measured monthly (birth to 6 mo) and at 8 and 12 mo. When the animals were 1, 5, and 8 mo old, liver copper and metallothionein concentrations, liver histology (by light and electron microscopy), and the number of Kupffer cells were assessed, and 67Cu retention was measured. Liver function was assessed by measurement of plasma alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase activities and protein, albumin, bilirubin, and blood urea nitrogen concentrations. 67Cu retention was 19.2% and 10.9% after 1 and 5 mo of copper treatment, respectively, compared with approximately 75% in controls at age 2 mo. At age 8 mo, 67Cu retention was 22.9% in copper-treated animals and 31.5% in controls. Liver histology remained normal by light microscopy, with mild ultrastructural signs of cell damage at 5 mo. Liver copper concentration was 4711, 1139, and 498 microg/g dry tissue at 1, 5, and 8 mo, respectively, in copper-treated animals and 250 microg/g at 2 mo in controls. Measurements could not be completed in all animals. No clinical evidence of copper toxicity was observed. Copper absorption was down-regulated; increases in liver copper content at ages 1 and 5 mo did not result in histologic damage. Ultrastructural changes at age 5 mo could signal early cellular damage.

  1. Dose and Effect Thresholds for Early Key Events in a Mode of PPARa-Mediated Action

    EPA Science Inventory

    ABSTRACT Strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. T...

  2. Synergistic effect of topography, surface chemistry and conductivity of the electrospun nanofibrous scaffold on cellular response of PC12 cells.

    PubMed

    Tian, Lingling; Prabhakaran, Molamma P; Hu, Jue; Chen, Menglin; Besenbacher, Flemming; Ramakrishna, Seeram

    2016-09-01

    Electrospun nanofibrous nerve implants is a promising therapy for peripheral nerve injury, and its performance can be tailored by chemical cues, topographical features as well as electrical properties. In this paper, a surface modified, electrically conductive, aligned nanofibrous scaffold composed of poly (lactic acid) (PLA) and polypyrrole (Ppy), referred to as o-PLAPpy_A, was fabricated for nerve regeneration. The morphology, surface chemistry and hydrophilicity of nanofibers were characterized by Scanning Electron Microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and water contact angle, respectively. The effects of these nanofibers on neuronal differentiation using PC12 cells were evaluated. A hydrophilic surface was created by Poly-ornithine coating, which was able to provide a better environment for cell attachment, and furthermore aligned fibers were proved to be able to guide PC12 cells grow along the fiber direction and be beneficial for neurite outgrowth. The cellular response of PC12 cells to pulsed electrical stimulation was evaluated by NF 200 and alpha tubulin expression, indicating that electrical stimulation with a voltage of 40mV could enhance the neurite outgrowth. The PC12 cells stimulated with electrical shock showed greater level of neurite outgrowth and smaller cell body size. Moreover, the PC12 cells under electrical stimulation showed better viability. In summary, the o-PLAPpy_A nanofibrous scaffold supported the attachment, proliferation and differentiation of PC12 cells in the absence of electrical stimulation, which could be potential candidate for nerve regeneration applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Investigation of microgravity effects on basic imune functions on the cellular level - The TRIPLELUX-B experiment

    NASA Astrophysics Data System (ADS)

    Unruh, Eckehardt; Hansen, Peter-Diedrich

    Hemocytes are the primary defence of the Blue Mussel against invading microorganisms and foreign particles. The hemocytes of mussels as part of the immune system of invertebrates has not been studied so far in space. The choice of the phagocytes from invertebrates is justified by the claim to study the universal validity of innate immune responses. The hemocytes of mussels have a lot in common with macrophages of higher organisms. They are able to detect the presence of microorganisms and kill these microorganisms by phagocytosis. The phagocy-tosis related production of ROS will be stimulated with opsonised zymosan. The hemocytes will be stored frozen and reconstituted in-flight for the experiment. The signals of the im-muno cellular responses are translated into luminescence as a rapid optical reporter system. The primary aim of Triplelux B is to investigate under space flight conditions the effect of microgravity on the ability of isolated Blue Mussel hemocytes to perform phagocytosis. As a secondery objectiv, the results expected will allow to conclude whether the observed responses are caused by microgravity and/or radiation (change in permeability, endpoints in genotoxicity: DNA unwinding). The TRIPLELUX-B Experiment contributes to risk assessment concerning immunotoxicity under space flight conditions. The components of the fully automated AEC (Advanced Experimental Containment) will be demonstrated. The AEC of the TRIPLELUX-B experiment will contribute to a real time operational monitoring for immunotoxicity testing for earth. Blue mussels have been used repeatedly for monitoring imunotoxicity and genotoxicity in coastal waters. Based on the AEC an automatet measuring device will allow "real time monitoring" providing observations of immunotoxicity in coastal and inland waters.

  4. Early effectiveness of endoscopic posterior urethra primary alignment.

    PubMed

    Kim, Fernando J; Pompeo, Alexandre; Sehrt, David; Molina, Wilson R; Mariano da Costa, Renato M; Juliano, Cesar; Moore, Ernest E; Stahel, Philip F

    2013-08-01

    Posterior urethra primary realignment (PUPR) after complete transection may decrease the gap between the ends of the transected urethra, tamponade the retropubic bleeding, and optimize urinary drainage without the need of suprapubic catheter facilitating concurrent pelvic orthopedic and trauma procedures. Historically, the distorted anatomy after pelvic trauma has been a major surgical challenge. The purpose of the study was to assess the relationship of the severity of the pelvic fracture to the success of endoscopic and immediate PUPR following complete posterior urethral disruption using the Young-Burgess classification system. A review of our Level I trauma center database for patients diagnosed with pelvic fracture and complete posterior urethral disruption from January 2005 to April 2012 was performed. Pelvic fracture severity was categorized according to the Young-Burgees classification system. Management consisted of suprapubic catheter insertion at diagnosis followed by early urethral realignment when the patient was clinically stable. Failure of realignment was defined as inability to achieve urethral continuity with Foley catheterization. Clinical follow-up consisted of radiologic, pressure studies and cystoscopic evaluation. A total of 481 patients with pelvic trauma from our trauma registry were screened initially, and 18 (3.7%) were diagnosed with a complete posterior urethral disruption. A total of 15 primary realignments (83.3%) were performed all within 5 days of trauma. The success rate of early realignment was 100%. There was no correlation between the type of pelvic ring fracture and the success of PUPR. Postoperatively, 8 patients (53.3%) developed urethral strictures, 3 patients (20.0%) developed incontinence, and 7 patients (46.7%) reported erectile dysfunction after the trauma. The mean follow-up of these patients was 31.8 months. Endoscopic PUPR may be an effective option for the treatment of complete posterior urethral disruption and

  5. Effect and possible mechanism of monocyte-derived VEGF on monocyte-endothelial cellular adhesion after electrical burns.

    PubMed

    Ruan, Qiongfang; Zhao, Chaoli; Ye, Ziqing; Ruan, Jingjing; Xie, Qionghui; Xie, Weiguo

    2015-06-01

    One of the major obstacles in the treatment of severe electrical burns is properly handling the resulting uncontrolled inflammation. Such inflammation often causes secondary injury and necrosis, thus complicating patient outcomes. Vascular endothelial grow factor (VEGF) has emerged as an important mediator for the recruitment of monocytes to the site inflammation. This study was designed to explore the effects and possible mechanism of VEGF on monocyte-endothelial cellular adhesion. To do so, we used a cultured human monocytic cell line (THP-1) that was stimulated with serum derived from rats that had received electrical burns. Serum was obtained from rats that had received electrical burns. Both the VEGF and soluble flt-1 (sflt-1) concentrations of the serum were determined by double-antibody sandwich ELISA. The concentrations of VEGF, sflt-1, and TNF-α obtained from the cell-free cultured supernatant of THP-1 cells that had been exposed to the serum were then determined by double-antibody sandwich ELISA. Serum-stimulated THP-1 cells were added to wells with a monolayer of endothelial cells to detect the level of monocyte-endothelial cells adhesion. Finally, the state of phosphorylation of AKT was determined by Western blotting. Both in vivo and in vitro studies showed that compared to controls, the levels of VEGF were significantly increased after electrical burns. This increased was accompanied by a reduction of sflt-1 levels. Furthermore, the serum of rats that had received electrical burns was able to both activate monocytes to secrete TNF-α and enhance monocyte-endothelial cell adhesion. Treatment with the serum also resulted in an up-regulation of the phosphorylation of AKT, but had no effect on the total levels of AKT. Phosphatidylinositide 3-kinases (PI3K) inhibition decreased the number of THP-1 cells that were adhered to endothelial cells. Finally, sequestering VEGF with sflt-1 was able to reduce the effect on monocyte-endothelial cells adhesion by

  6. The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid.

    PubMed

    Hassanin, Kamel M A; Abd El-Kawi, Samraa H; Hashem, Khalid S

    2013-01-01

    Nanotechnology has enabled researchers to synthesize nanosize particles that possess increased surface areas. Compared to conventional microparticles, it has resulted in increased interactions with biological targets. The objective of this study was to determine the protective ability of selenium nanoparticles against hexavalent chromium-induced thyrotoxicity. Twenty male rats were used in the study, and arbitrarily assigned to four groups. Group 1 was the control group, and was given phosphate-buffered saline. Group 2 was the chromium-treated group and was given K2Cr2O7 60 μg/kg body weight intraperitoneally as a single dose on the third day of administration. Group 3 was the nano-selenium-treated group and was given selenium nanoparticles (size 3-20 nm) 0.5 mg/kg body weight intraperitoneally daily for 5 consecutive days. Group 4 was the nano-selenium chromium-treated group, which received selenium nanoparticles for 5 days and a single dose of K2Cr2O7 on the third day of administration. Blood samples were collected from rats for measuring thyroid hormones (free triiodothyronine [T3] and free thyroxine [T4]) and oxidative and antioxidant parameters (malondialdehyde [MDA], reduced glutathione [GSH], catalase, and superoxide dismutase [SOD]). Upon dissection, thyroid glands were taken for histopathological examination by using paraffin preparations stained with hematoxylin and eosin (H&E) and Masson's trichrome. Immunohistochemical staining was performed for detecting cellular proliferation using Ki67 antibodies. The present study shows that K2Cr2O7 has a toxic effect on the thyroid gland as a result of inducing a marked oxidative damage and release of reactive oxygen species. This was shown by the significant decrease in free T3 and T4 and GSH levels, which was accompanied by significant increases in catalase, SOD, and MDA in the chromium-treated group compared to the control group. Se nanoparticles have a protective effect on K2Cr2O7-induced thyroid damage, as a

  7. The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid

    PubMed Central

    Hassanin, Kamel MA; El-Kawi, Samraa H Abd; Hashem, Khalid S

    2013-01-01

    Background Nanotechnology has enabled researchers to synthesize nanosize particles that possess increased surface areas. Compared to conventional microparticles, it has resulted in increased interactions with biological targets. Objective The objective of this study was to determine the protective ability of selenium nanoparticles against hexavalent chromium-induced thyrotoxicity. Design Twenty male rats were used in the study, and arbitrarily assigned to four groups. Group 1 was the control group, and was given phosphate-buffered saline. Group 2 was the chromium-treated group and was given K2Cr2O7 60 μg/kg body weight intraperitoneally as a single dose on the third day of administration. Group 3 was the nano-selenium-treated group and was given selenium nanoparticles (size 3–20 nm) 0.5 mg/kg body weight intraperitoneally daily for 5 consecutive days. Group 4 was the nano-selenium chromium-treated group, which received selenium nanoparticles for 5 days and a single dose of K2Cr2O7 on the third day of administration. Materials and methods Blood samples were collected from rats for measuring thyroid hormones (free triiodothyronine [T3] and free thyroxine [T4]) and oxidative and antioxidant parameter