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Sample records for activation induces type

  1. Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation

    Napoletano, Chiara; Zizzari, Ilaria G; Rughetti, Aurelia;

    2012-01-01

    Dendritic cells (DCs) sense the microenvironment through several types of receptors recognizing pathogen-associated molecular patterns. In particular, C-type lectins, expressed by distinct subsets of DCs, recognize and internalize specific carbohydrate antigen in a Ca(2+) -dependent manner. Targe...

  2. Eudesmane-type sesquiterpenoids from Salvia plebeia inhibit IL-6-induced STAT3 activation.

    Jang, Hyun-Jae; Oh, Hyun-Mee; Hwang, Joo Tae; Kim, Mi-Hwa; Lee, Soyoung; Jung, Kyungsook; Kim, Young-Ho; Lee, Seung Woong; Rho, Mun-Chual

    2016-10-01

    Seven eudesmane-type sesquiterpenoid lactones and the known plebeiolide C were isolated from an ethanol-soluble extract of the aerial parts of Salvia plebeia R. Br. Their structures were determined via NMR and MS, and their absolute configurations were elucidated using ECD, and X-ray crystallographic analysis, as well as the modified Mosher ester method. All isolates were evaluated for their inhibitory effects on IL6-induced STAT3 promoter activation in stably transfected Hep3B cells. Of these isolates, eudebeiolide D exhibited an inhibitory effect with the IC50 value of 1.1 μM. PMID:27506573

  3. Tissue-type plasminogen activator induces synaptic vesicle endocytosis in cerebral cortical neurons.

    Yepes, M; Wu, F; Torre, E; Cuellar-Giraldo, D; Jia, D; Cheng, L

    2016-04-01

    The release of the serine proteinase tissue-type plasminogen activator (tPA) from the presynaptic terminal of cerebral cortical neurons plays a central role in the development of synaptic plasticity, adaptation to metabolic stress and neuronal survival. Our earlier studies indicate that by inducing the recruitment of the cytoskeletal protein βII-spectrin and voltage-gated calcium channels to the active zone, tPA promotes Ca(2+)-dependent translocation of synaptic vesicles (SVs) to the synaptic release site where they release their load of neurotransmitters into the synaptic cleft. Here we used a combination of in vivo and in vitro experiments to investigate whether this effect leads to depletion of SVs in the presynaptic terminal. Our data indicate that tPA promotes SV endocytosis via a mechanism that does not require the conversion of plasminogen into plasmin. Instead, we show that tPA induces calcineurin-mediated dynamin I dephosphorylation, which is followed by dynamin I-induced recruitment of the actin-binding protein profilin II to the presynaptic membrane, and profilin II-induced F-actin formation. We report that this tPA-induced sequence of events leads to the association of newly formed SVs with F-actin clusters in the endocytic zone. In summary, the data presented here indicate that following the exocytotic release of neurotransmitters tPA activates the mechanism whereby SVs are retrieved from the presynaptic membrane and endocytosed to replenish the pool of vesicles available for a new cycle of exocytosis. Together, these results indicate that in murine cerebral cortical neurons tPA plays a central role coupling SVs exocytosis and endocytosis. PMID:26820595

  4. Antidiabetic Activity of Benzopyrone Analogues in Nicotinamide-Streptozotocin Induced Type 2 Diabetes in Rats

    Yogendra Nayak

    2014-01-01

    Full Text Available Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D was induced in Wistar rats by streptozotocin (60 mg/kg, i.p. followed by nicotinamide (120 mg/kg i.p.. Rats having fasting blood glucose (FBG >200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glucose tolerance test (OGTT, and insulin tolerance test (ITT were determined on 21st day after induction of T2D. Plasma lipids and serum insulin were estimated. Homeostatic model assessment (HOMA-IR was then calculated from serum insulin. Rats were sacrificed and pancreas was isolated for histopathological observations. Oxidative stress markers were estimated in liver homogenate. Quercetin, a natural product with benzopyrone ring, showed significant hypoglycemic activity comparable to glibenclamide. Treatment with test compounds lowered the FBG and insulin resistance was significant alleviated as determined by OGTT, HOMA-IR, and ITT. There was significant normalisation of liver antioxidant enzymes compared to diabetic rats indicating that all the synthesised benzopyrone analogues are beneficial in reducing oxidative stress and are on par with the standard quercetin and glibenclamide in experimental T2D.

  5. Relationships between optical aggregometry (type Born) and flow cytometry in evaluating ADP-induced platelet activation

    Sbrana, Silverio; Della Pina, Francesca; Rizza, Antonio; Buffa, Manuela; De Filippis, Rossella; Gianetti, Jacopo; Clerico, Aldo

    2008-01-01

    Background: Platelet response to activating agents is used to monitor the efficacy of anti-aggregation therapies. The aim of our study has been to demonstrate the existence of relationships between early events of ADP-induced platelet activation, measured by flow cytometry and platelet-rich plasma aggregation,quantified by optical aggregometry. Methods: We evaluated peripheral blood of 12 donors. The following parameters were quantified by cytometry after stimulation with adenosine diphosphat...

  6. Role of plasminogen activator inhibitor type-1 in radiation-induced normal tissues injury

    Radiotherapy is an essential tool for cancer treatment, but there is a balance between benefits and risks related to the use of ionizing radiation: the objective is to deliver a maximum dose to the tumour to destroy or to sterilize it while protecting surrounding normal tissues. Radio-induced damages to normal tissues are therefore a limiting factor when increasing the dose delivered to the tumour. One of the objectives of this research thesis is to bring to the fore a relationship between the initiation of lesions and the development of late damages, more particularly in the intestine, and to identify the involved molecular actors and their inter-connectivity. After a first part presenting ionizing radiation, describing biological effects of ionizing radiation and their use in radiotherapy, presenting the intestine and the endothelium and discussing the intestine radio-sensitivity, discussing the radio-induced intestine damages and radiotherapy-induced complications, and presenting the plasminogen activator inhibitor (PAI-1) and its behaviour in presence of ionizing radiation, two articles are reproduced. The first one addresses the effect of a pharmacological inhibition and of genetic deficiency in PAI-1 on the evolution of radio-induced intestine lesions. The second one discusses the fact that radio-induced PAI-1-related death of endothelial cells determines the severity of early radio-induced intestine lesions

  7. Task-Induced Brain Activity Patterns in Type 2 Diabetes: A Potential Biomarker for Cognitive Decline

    Marder, Thomas J.; Flores, Veronica L.; Bolo, Nicolas R.; Hoogenboom, Wouter S.; Simonson, Donald C.; Jacobson, Alan M.; Foote, Sarah E.; Martha E. Shenton; Sperling, Reisa A.; Musen, Gail

    2014-01-01

    Patients with type 2 diabetes demonstrate reduced functional connectivity within the resting state default mode network (DMN), which may signal heightened risk for cognitive decline. In other populations at risk for cognitive decline, additional magnetic resonance imaging abnormalities are evident during task performance, including impaired deactivation of the DMN and reduced activation of task-relevant regions. We investigated whether middle-aged type 2 diabetic patients show these brain act...

  8. In vivo gene delivery of urokinase-type plasminogen activator with regulatable lentivirus induces behavioural changes in chronic cocaine administration

    Bahi, Amine; Boyer, Frederic; Gumy, Christèle; Kafri, Tal; Dreyer, Jean-Luc

    2005-01-01

    Serine proteases play a key function in extracellular processes affecting central nervous system plasticity. Recently, the role of extracellular proteolytic processes in regulating synaptic structure and function has been described. However, to date direct evidence linking extracellular serine protease activity with drug-related behavioural changes has not been documented. Importantly, in a screening for genes induced after drug treatment we found that urokinase plasminogen-type activator (uP...

  9. Antidiabetic Activity of Benzopyrone Analogues in Nicotinamide-Streptozotocin Induced Type 2 Diabetes in Rats

    Yogendra Nayak; Venkatachalam Hillemane; Vijay Kumar Daroji; Jayashree, B. S.; Unnikrishnan, M. K.

    2014-01-01

    Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D) was induced in Wistar rats by streptozotocin (60 mg/kg, i.p.) followed by nicotinamide (120 mg/kg i.p.). Rats having fasting blood glucose (FBG) >200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glu...

  10. Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

    The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection

  11. Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

    Takeda, Kazuyo [Microscopy and Imaging Core Facility, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD (United States); Adhikari, Rewati [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); Yamada, Kenneth M. [National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Dhawan, Subhash, E-mail: subhash.dhawan@fda.hhs.gov [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

    2015-08-14

    The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection.

  12. Physical activity-induced remodeling of vasculature in skeletal muscle: role in treatment of type 2 diabetes.

    Laughlin, M Harold

    2016-01-01

    This manuscript summarizes and discusses adaptations of skeletal muscle vasculature induced by physical activity and applies this understanding to benefits of exercise in prevention and treatment of type 2 diabetes (T2D). Arteriolar trees of skeletal muscle are heterogeneous. Exercise training increases capillary exchange and blood flow capacities. The distribution of vascular adaptation to different types of exercise training are influenced by muscle fiber type composition and fiber recruitment patterns that produce different modes of exercise. Thus training-induced adaptations in vascular structure and vascular control in skeletal muscle are not homogeneously distributed throughout skeletal muscle or along the arteriolar tree within a muscle. Results summarized indicate that similar principles apply to vascular adaptation in skeletal muscle in T2D. It is concluded that exercise training-induced changes in vascular gene expression differ along the arteriolar tree and by skeletal muscle fiber type composition. Results suggest that it is unlikely that hemodynamic forces are the only exercise-induced signals mediating the regulation of vascular gene expression. In patients with T2D, exercise training is perhaps the most effective treatment of the many related symptoms. Training-induced changes in the vasculature and in insulin signaling in the muscle fibers and vasculature augment glucose and insulin delivery as well as glucose uptake. If these adaptations occur in a sufficient amount of muscle mass, exposure to hyperglycemia and hyperinsulinemia will decrease along with the risk of microvascular complications throughout the body. It is postulated that exercise sessions in programs of sufficient duration, that engage as much skeletal muscle mass as possible, and that recruit as many muscle fibers within each muscle as possible will produce the greatest benefit. The added benefit of combined resistance and aerobic training programs and of high-intensity exercise

  13. Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U-937 lymphoma cells

    1987-01-01

    The tumor-promoting phorbol ester PMA induces changes in the histiocytic human lymphoma cell line U-937 akin to cellular differentiation (Ralph, P., N. Williams, M. A. S. Moore, and P. B. Litcofsky, 1982, Cell. Immunol., 71:215-223) and concomitantly stimulates the biosynthesis of plasminogen activator inhibitor 2 (PAI 2) and of urokinase-type plasminogen activator (u-PA). PAI 2 is found in a nonglycosylated intracellular and a glycosylated secreted form. The former appears to be identical to...

  14. Oral hypoglycaemic activity of Ipomoea aquatica in streptozotocin-induced, diabetic wistar rats and Type II diabetics.

    Malalavidhane, T S; Wickramasinghe, S M D N; Perera, M S A; Jansz, E R

    2003-11-01

    Ipomoea aquatica Forsk is a common green leafy vegetable consumed in many parts of the world. The present study was designed to investigate the oral hypoglycaemic activity of Ipomea aquatica in streptozotocin induced diabetic Wistar rats, and Type II diabetic patients. Experimental diabetes was induced with streptozotocin in Wistar rats. The rats were then divided into test and control groups. In addition to the standard feed given to both groups the test was fed with the shredded leaves of Ipomoea aquatica (3.4 g/kg) for one week. Type II diabetic patients were subjected to a glucose challenge before and after a single dose of blended I. aquatica. Patients acted as their own controls. The results revealed that consumption of the shredded, fresh, edible portion of I. aquatica for one week, effectively reduced the fasting blood sugar level of streptozotocin-induced diabetic rats (p = 0.01). When subjected to a glucose challenge, the Type II diabetic subjects showed a significant reduction (p = 0.001) in the serum glucose concentration 2 h after the glucose load. However, it was not significantly reduced at 1 h (p < 0.09) post glucose load. There was a 29.4% decrease in the serum glucose concentration of the diabetic patients when treated with the plant extract. PMID:14595595

  15. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation

    Tarui, Takehiko; Akakura, Nobuaki; Majumdar, Mousumi; Andronicos, Nicholas; Takagi, Junichi; Mazar, Andrew P.; Bdeir, Khalil; Kuo, Alice; Yarovoi, Serge V.; Cines, Douglas B.; Takada, Yoshikazu

    2006-01-01

    It has been questioned whether there are receptors for urokinase-type plasminogen activator (uPA) that facilitate plasminogen activation other than the high affinity uPA receptor (uPAR/CD87) since studies of uPAR knockout mice did not support a major role of uPAR in plasminogen activation. uPA also promotes cell adhesion, chemotaxis, and proliferation besides plasminogen activation. These uPA-induced signaling events are not mediated by uPAR, but mediated by unidentified, lower-affinity recep...

  16. Type IV secretion-dependent activation of host MAP kinases induces an increased proinflammatory cytokine response to Legionella pneumophila.

    Sunny Shin

    2008-11-01

    Full Text Available The immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS, induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-kappaB activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria.

  17. CCl4 induces tissue-type plasminogen activator in rat brain; protective effects of oregano, rosemary or vitamin E.

    Lavrentiadou, Sophia N; Tsantarliotou, Maria P; Zervos, Ioannis A; Nikolaidis, Efstathios; Georgiadis, Marios P; Taitzoglou, Ioannis A

    2013-11-01

    The high metabolic rate and relatively low antioxidant defenses of the lipid-rich brain tissue render it highly susceptible to reactive oxygen species (ROS) and oxidative stress, whereas the implication of ROS in the pathogenesis of several diseases in the central nervous system is well-established. The plasminogen activator (PA) system is a key modulator of extracellular proteolysis, extracellular matrix remodeling and neuronal cell signaling and has been implicated in the pathogenesis of these diseases. This study evaluates the role of tissue-type PA (t-PA) in oxidative stress and the protective role of dietary antioxidants in the rat brain. We used the CCl4 experimental model of ROS-induced lipid peroxidation and evaluated the antioxidant effect of oregano, rosemary or vitamin E. CCl4-treated Wistar rats exhibited elevated brain t-PA activity, which was decreased upon long-term administration of oregano, rosemary or vitamin E. PA inhibitor-1 (PAI-1) activity was also slightly elevated by CCl4, but this increase was not affected by the antioxidants. We hypothesize that the CCl4-induced t-PA activity indicates extracellular proteolytic activity that may be linked to neuronal cell death and brain damage. Vitamin E or antioxidants present in oregano or rosemary are effective in inhibiting t-PA elevation and can be considered as a potential protection against neuronal damage. PMID:23831191

  18. Effects of urokinase-type plasminogen activator in the acquisition, expression and reinstatement of cocaine-induced conditioned-place preference

    Bahi, Amine; Kusnecov, Alexander W; Dreyer, Jean-Luc

    2008-01-01

    Cocaine and many other psychostimulants strongly induce urokinase-type plasminogen activator (uPA) expression in the mesolimbic dopaminergic pathway, which plays a major role in drug-mediated behavioral plasticity [Bahi A, Boyer F, Gumy C, Kafri T, Dreyer JL. In vivo gene delivery of urokinase-type plasminogen activator with regulatable lentivirus induces behavioral changes in chronic cocaine administration. Eur J Neurosci 2004;20:3473–88; Bahi A, Boyer F, Kafri T, Dreyer JL. Silencing urokin...

  19. Measurements of induced activity in type 316 stainless steel by irradiation in D-T neutron fields

    Experiments on induced activities in type 316 stainless steel (SUS316) have been performed to verify an induced activity calculation code system, THIDA, by using the FNS facility. Samples of 10 mm /phi/ x 2 mm t SUS316 were irradiated in three different D-T neutron fields. One sample was positioned at 10 cm from the target without any assembly around it and the other two placed inside the Li2O-C pseudo-spherical blanket assembly. After the irradiation, spectra of gamma-rays emitted from produced activities in each sample were measured by using a 60 cm3 Ge(Li) detector following the cooling times from 10 min. to about one month. The gamma-ray spectra were compared with those calculated by THIDA. All measured total gammaray intensities agreed with calculated ones within 15 % except one case. Though there are some disagreements in the individual gamma-ray intensities, the agreements are good as a whole

  20. An experimental study of induced activity in type 316 stainless steel by irradiation in D-T neutron fields

    Experiments on induced activities in type 316 stainless steel (SUS316) have been performed in order to verify an induced activity calculation code system, THIDA, by using the FNS facility. Sample of 10 mm diameter x 2 mm t SUS316 were irradiated in three different D-T neutron fields. One sample was positioned at 10 cm from the target with no assembly around it and the other two placed inside the Li2O-C pseudospherical blanket assembly. After irradiation, spectra of gamma-rays emitted from produced activities in each sample were successively measured by using a 60 cm3 Ge(Li) detector following the cooling times from 10 min to about one month. The gamma-ray spectra and relative doses were compared with those calculated by THIDA. All the measured and calculated total gamma-ray intensities and relative doses agreed with each other within 15 % with one exception. Though the agreements were good as a whole, there were some disagreements in the individual gamma-ray intensities. The disagreements were investigated from the viewpoints of the THIDA code system and their nuclear data library. (author)

  1. An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity

    Ank, Nina; Iversen, Marie B; Bartholdy, Christina;

    2008-01-01

    Type III IFNs (IFN-lambda/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both types I and III IFNs after TLR stimulation or virus infection, whereas the ability of cells to respond to IFN-lambda w...

  2. Simultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation

    Kaznelson, Dorte Wissing; Bruun, Silas; Monrad, Astrid;

    2004-01-01

    Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation and induc...

  3. Thyroid dysfunction induced by recombinant interferon-alpha therapy for chronic active type C hepatitis

    The aim of this study was to assess the frequency and types of thyroid therapy in patients of Chronic dysfunction that develops during IFN- Hepatitis C. The study was carried out on a total of 50 patients of chronic therapy. In addition 50 patients with hepatitis C on recombinant IFN- chronic hepatitis C, not on any antiviral treatment, were included as controls. After informed consent, clinical history was obtained, physical examination was done and findings recorded on a pre-designed proforma. Blood sampling was done for thyroid profile at the beginning of interferon therapy, at 12 weeks and finally at 24 weeks. Thyroid dysfunction (TD) was observed in 14% (n=7) of the patients on antiviral therapy for CHC (n=50). Amongst these seven patients with TD, hypothyroidism was observed in 5 and hyperthyroidism in 2 patients. In contrast the frequency of thyroid dysfunction observed in control group (n=50) was 2%. The frequency of thyroid dysfunction in patients of chronic hepatitis C treated with interferon approaches 14%, with hypothyroidism being the more commonly observed pattern. (author)

  4. Active inhibition of herpes simplex virus type 1-induced cell fusion

    Bzik, D.J.; Person, S.; Read, G.S.

    1982-01-01

    Previous studies have demonstrated that syn mutant-infected cells fuse less well with nonsyncytial virus-infected cells than with uninfected cells, a phenomenon defined as function inhibition. The present study characterizes the kinetics as well as the requirements for expression of fusion inhibition. Initially, the capacity of sparse syn mutant-infected cells to fuse with uninfected surrounding cells was determined throughout infection. Of seven syn mutants examined, including representatives with alterations in two different viral genes that affect cell fusion, all showed an increase in fusion capacity up to 12 hr after infection and a decrease at later times. Fusion inhibition was examined in experiments employing sparse syn20-infected cells which had been incubated to a maximum fusion capacity; it was shown that surrounding cells infected with KOS, the parent of syn20, began to inhibit fusion by the syn20-infected cells at about 4 hr after infection, and that the maximum ability to inhibit fusion was attained at about 6 hr after infection. The metabolic blocking agents actinomycin D (RNA), cycloheximide (protein), 2-deoxyglucose, and tunicamycin (glycoslyation of glycoproteins) all showed the ability to inhibit the expression of fusion inhibition by KOS-infected cells if added shortly after infection. It is concluded that fusion inhibition is an active process that requires the synthesis of RNA, proteins, and glycoproteins. 17 references, 3 figures, 2 tables.

  5. Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

    Highlights: ► Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. ► Staurosporine mediates uPA activation during RGC differentiation in vitro. ► Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. ► Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that uPA plays a role in the staurosporine-mediated stimulation of RGC differentiation.

  6. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation.

    Tarui, Takehiko; Akakura, Nobuaki; Majumdar, Mousumi; Andronicos, Nicholas; Takagi, Junichi; Mazar, Andrew P; Bdeir, Khalil; Kuo, Alice; Yarovoi, Serge V; Cines, Douglas B; Takada, Yoshikazu

    2006-03-01

    It has been questioned whether there are receptors for urokinase-type plasminogen activator (uPA) that facilitate plasminogen activation other than the high affinity uPA receptor (uPAR/CD87) since studies of uPAR knockout mice did not support a major role of uPAR in plasminogen activation. uPA also promotes cell adhesion, chemotaxis, and proliferation besides plasminogen activation. These uPA-induced signaling events are not mediated by uPAR, but mediated by unidentified, lower-affinity receptors for the uPA kringle. We found that uPA binds specifically to integrin alpha v beta 3 on CHO cells depleted of uPAR. The binding of uPA to alpha v beta 3 required the uPA kringle domain. The isolated uPA kringle domain binds specifically to purified, recombinant soluble, and cell surface alpha v beta 3, and other integrins (alpha 4 beta 1 and alpha 9 beta 1), and induced migration of CHO cells in an alpha v beta 3-dependent manner. The binding of the uPA kringle to alpha v beta 3 and uPA kringle-induced alpha v beta 3-dependent cell migration were blocked by homologous plasminogen kringles 1-3 or 1-4 (angiostatin), a known integrin antagonist. We studied whether the binding of uPA to integrin alpha v beta 3 through the kringle domain plays a role in plasminogen activation. On CHO cell depleted of uPAR, uPA enhanced plasminogen activation in a kringle and alpha v beta 3-dependent manner. Endothelial cells bound to and migrated on uPA and uPA kringle in an alpha v beta 3-dependent manner. These results suggest that uPA binding to integrins through the kringle domain plays an important role in both plasminogen activation and uPA-induced intracellular signaling. The uPA kringle-integrin interaction may represent a novel therapeutic target for cancer, inflammation, and vascular remodeling. PMID:16525582

  7. Indications for different types of brittle failure due to active coal mining using waveform similarities of induced seismic events

    Wehling-Benatelli, S.; Becker, D.; Bischoff, M.; Friederich, W.; Meier, T.

    2013-10-01

    Longwall mining activity in the Ruhr coal mining district leads to mining-induced seismicity. For detailed studies the seismicity of a single longwall panel beneath the town of Hamm-Herringen in the eastern Ruhr area was monitored between June 2006 and July 2007 with a dense temporary network of 15 seismic stations. More than 7000 seismic events with magnitudes between -1.7 ≤ ML ≤ 2.0 were detected and localized in this period. Most of the events occurred in the vicinity of the moving longwall face. In order to find possible differences in the brittle failure types of these events an association of the events to distinct clusters is performed based on their waveform characteristics. This task is carried out using a new clustering algorithm utilizing a network similarity matrix which is created by combining all available 3-component single station similarity matrices. The resultant network matrix is then sorted with respect to the similarity of its rows leading to a sorted matrix immediately indicating the clustering of the event catalogue. Finally, clusters of similar events are extracted by visual inspection. This approach results in the identification of several large clusters which are distinct with respect to their spatial and temporal characteristics as well as their frequency magnitude distributions. Comparable clusters are also found with a conventional single linkage approach, however, the new routine seems to be able to associate more events to specific clusters without merging the clusters. The nine largest observed clusters can be tentatively divided into three different groups that indicate different types of brittle failure. The first group consists of the two largest clusters which constitute more than half of all recorded events. Results of a relative relocation using cross-correlation data suggest that these events are confined to the extent of the mined out longwall and cluster close to the edges of the active longwall at the depth of active

  8. Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

    Kim, Yeoun-Hee [Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Chang, Yongmin [Department of Molecular Medicine, Kyungpook National University College of Medicine, Kyungpook National University, 200 Dongduk-Ro Jung-Gu, Daegu 700-714 (Korea, Republic of); Jung, Jae-Chang, E-mail: jcjung@knu.ac.kr [Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. Black-Right-Pointing-Pointer Staurosporine mediates uPA activation during RGC differentiation in vitro. Black-Right-Pointing-Pointer Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. Black-Right-Pointing-Pointer Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that

  9. Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo

    Ank, Nina; West, Hans; Bartholdy, Christina;

    2006-01-01

    Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The IFN-lambdas were-unlike alpha/beta interferon (IFN......-alpha potently restricted both viruses. Using three murine models for generalized virus infections, we found that while recombinant IFN-alpha reduced the viral load after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2, treatment with recombinant IFN-lambda in vivo did not affect viral......-alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN...

  10. Lambda Interferon (IFN-gamma), a Type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo

    Ank, Nina; West, Hans; Bartholdy, C.;

    2006-01-01

    Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The IFN-lambdas were-unlike alpha/beta interferon (IFN......-alpha potently restricted both viruses. Using three murine models for generalized virus infections, we found that while recombinant IFN-alpha reduced the viral load after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2, treatment with recombinant IFN-lambda in vivo did not affect viral......-alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN...

  11. Protective role of Kalpaamruthaa in type II diabetes mellitus-induced cardiovascular disease through the modulation of protease-activated receptor-1

    Raja Latha; Palanivelu Shanthi; Panchanadham Sachdanandam

    2015-01-01

    Background: Kalpaamruthaa (KA) is a formulatory herbal preparation has beneficial antioxidant, anti-apoptotic and anti-inflammatory properties against cardiovascular damage (CVD). Objective: The present study was undertaken to investigate the protective role of KA in type II diabetes mellitus-induced CVD through the modulation of protease-activated receptor-1 (PAR1). Materials and Methods: CVD was developed in 8 weeks after type II diabetes mellitus induction with high fat diet (2 weeks) and ...

  12. Mitogenic activity of the adenovirus type 12 E1A gene induced by hormones in rat cells.

    Oda, K.; Masuda-Murata, M; Shiroki, K; Handa, H.

    1986-01-01

    Several lines of rat 3Y1 cells in which expression of the adenovirus type 12 E1A gene can be regulated by dexamethasone were established by introduction of recombinant vector DNA containing the adenovirus type 12 E1A gene placed downstream of the hormone-inducible promoter of mouse mammary tumor virus. These cell lines (gMA cells) produced low basal levels of the E1A transcripts and proteins in normal medium and much higher levels upon addition of dexamethasone to the medium. When dexamethaso...

  13. Biological Activities of Chinese Propolis and Brazilian Propolis on Streptozotocin-Induced Type 1 Diabetes Mellitus in Rats

    Wei Zhu; Minli Chen; Qiyang Shou; Yinghua Li; Fuliang Hu

    2011-01-01

    Propolis is a bee-collected natural product and has been proven to have various bioactivities. This study tested the effects of Chinese propolis and Brazilian propolis on streptozotocin-induced type 1 diabetes mellitus in Sprague-Dawley rats. The results showed that Chinese propolis and Brazilian propolis significantly inhibited body weight loss and blood glucose increase in diabetic rats. In addition, Chinese propolis-treated rats showed an 8.4% reduction of glycated hemoglobin levels compar...

  14. C-type lectin receptor-induced NF-κB activation in innate immune and inflammatory responses

    Kingeter, Lara M.; Lin, Xin

    2012-01-01

    The C-type lectin receptors (CLRs) belong to a large family of proteins that contain a carbohydrate recognition domain (CRD) and calcium binding sites on their extracellular domains. Recent studies indicate that many CLRs, such as Dectin-1, Dectin-2 and Mincle, function as pattern recognition receptors (PRRs) recognizing carbohydrate ligands from infected microorganisms. Upon ligand binding, these CLRs induce multiple signal transduction cascades through their own immunoreceptor tyrosine-base...

  15. Cancer-induced Expansion and Activation of CD11b+Gr-1+ Cells Predispose Mice to Adenoviral-triggered Anaphylactoid-type Reactions

    Pande, Kalyan; Ueda, Roanna; Machemer, Todd; Sathe, Manjiri; Tsai,, J.F.; Brin, Elena; Delano, Matthew J; van Rooijen, Nico; McClanahan, Terrill K.; Talmadge, James E.; Moldawer, Lyle L; Phillips, Joseph H; Laface, Drake M.

    2009-01-01

    Intravascular delivery (1.5 × 109 particles and higher) of recombinant adenovirus (rAd) induces myeloid cell mediated, self-limiting hemodynamic responses in normal mice. However, we observed anaphylactoid-type reactions and exacerbated hemodynamic events following rAd injection in mice bearing malignant 4T1 mammary carcinoma. Because 4T1 tumors induce significant CD11b+Gr-1+ myeloid cell expansion and activation, we set to determine whether this causes rAd-induced exaggerated responses. When...

  16. Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U-937 lymphoma cells

    Genton, C.; Kruithof, E.K.; Schleuning, W.D.

    1987-03-01

    The tumor-promoting phorbol ester PMA induces changes in the histiocytic human lymphoma cell line U-937 akin to cellular differentiation and concomitantly stimulates the biosynthesis of plasminogen activator inhibitor 2 (PAI 2) and of urokinase-type plasminogen activator (u-PA). PAI 2 is found in a nonglycosylated intracellular and a glycosylated secreted form. The former appears to be identical to PAI 2 previously purified from placental extracts and large-scale U-937 cell cultures. The sixfold increase of PAI 2 antigen measured 24 h after PMA treatment in cell extracts and conditioned media is accompanied by an equal increase of active PAI 2 mRNA, whereas the 6 to 13-fold increase of u-PA antigen in the same samples is associated with only a 1.5-fold mRNA increase. The increase of PAI 2, but not of u-PA, biosynthesis requires transcription. A 50-fold molar excess of PAI 2 over u-PA is found in both extracts and conditioned media of PMA-treated cells. PAI 2 represents at least 0.3% of total de novo synthesized protein 24 h after induction with PMA. Thus, PAI 2, but not u-PA, is an abundant product of this precursor analogue of the mononuclear phagocyte lineage, and might represent a new marker for monocyte/macrophage differentiation.

  17. Protective role of Kalpaamruthaa in type II diabetes mellitus-induced cardiovascular disease through the modulation of protease-activated receptor-1

    Raja Latha

    2015-01-01

    Full Text Available Background: Kalpaamruthaa (KA is a formulatory herbal preparation has beneficial antioxidant, anti-apoptotic and anti-inflammatory properties against cardiovascular damage (CVD. Objective: The present study was undertaken to investigate the protective role of KA in type II diabetes mellitus-induced CVD through the modulation of protease-activated receptor-1 (PAR1. Materials and Methods: CVD was developed in 8 weeks after type II diabetes mellitus induction with high fat diet (2 weeks and low dose of streptozotocin (2 × 35 mg/kg b.w. i.p. in 24 h interval. CVD-induced rats treated with KA (200 mg/kg b.w. in 0.5 ml of olive oil orally for 4 weeks. Results: KA increased the activities of enzymatic antioxidants and the levels of non-enzymatic antioxidants in pancreas of CVD-induced rats. KA effectively reduced the lipid peroxides and carbonyl content in the pancreas of CVD-induced rats. KA reduced cellular damage by ameliorating the activities of marker enzymes in plasma, heart and liver. The protective nature of KA was further evidenced by histological observation in pancreas. Further, KA reduced CVD by decreasing the expression of PAR1 in heart. Conclusion: This study exhibits the defending role of KA in type II diabetes mellitus-induced CVD through altering PAR1.

  18. Mycobacterium tuberculosis MmsA, a novel immunostimulatory antigen, induces dendritic cell activation and promotes Th1 cell-type immune responses.

    Kim, Jong-Seok; Kim, Woo Sik; Choi, Hong-Hee; Kim, Hong Min; Kwon, Kee Woong; Han, Seung Jung; Cha, Seung Bin; Cho, Sang-Nae; Koh, Won-Jung; Shin, Sung Jae

    2015-01-01

    Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is an outstanding pathogen that modulates the host immune response. This inconvenient truth drives the continual identification of antigens that generate protective immunity, including Th1-type T cell immunity. Here, the contribution of methylmalonate semialdehyde dehydrogenase (MmsA, Rv0753c) of Mtb to immune responses was examined in the context of dendritic cell (DC) activation and T cell immunity both in vitro and in vivo. The results showed that MmsA induced DC activation by activating the MAPK and NF-κB signaling pathways. Additionally, MmsA-treated DCs activated naïve T cells, effectively polarized CD4(+) and CD8(+) T cells to secrete IFN-γ and IL-2, and induced T cell proliferation. These results indicate that MmsA is a novel DC maturation-inducing antigen that drives the Th1 immune response. Thus, MmsA was found to potentially regulate immune responses via DC activation toward Th1-type T cell immunity, enhancing our understanding of Mtb pathogenesis. PMID:26507911

  19. Transcriptional Regulation of Urokinase-type Plasminogen Activator Receptor by Hypoxia-Inducible Factor 1 Is Crucial for Invasion of Pancreatic and Liver Cancer

    Peter Büchler

    2009-02-01

    Full Text Available Angioinvasion is critical for metastasis with urokinase-type plasminogen activator receptor (uPAR and tumor hypoxia-activated hypoxia-inducible factor 1 (HIF-1 as key players. Transcriptional control of uPAR expression by HIF has never been reported. The aim of the present study, therefore, was to test whether tumor hypoxia-induced HIF expression may be linked to transcriptional activation of uPAR and dependent angioinvasion. We used human pancreatic cancer cells and a model of parental and derived HIF-1β-deficient mouse liver cancer cell lines and performed Northern blot analysis, nuclear runoff assays, electrophoretic mobility shift assay, polymerase chain reaction-generated deletion mutants, luciferase assays, Matrigel invasion assays, and in vivo angioinvasion assays in the chorioallantoic membrane of fertilized chicken eggs. Urokinase-type plasminogen activator receptor promoter analysis resulted in four putative HIF binding sites. Hypoxia strongly induced de novo transcription of uPAR mRNA. With sequential deletion mutants of the uPAR promoter, it was possible to identify one HIF binding site causing a nearly 200-fold increase in luciferase activity. Hypoxia enhanced the number of invading tumor cells in vitro and in vivo. In contrast, HIF-1β-deficient cells failed to upregulate uPAR expression, to activate luciferase activity, and to invade on hypoxia. Taken together, we show for the first time that uPAR is under transcriptional control of HIF and that this is important for hypoxia-induced metastasis.

  20. Nuclear envelope breakdown induced by herpes simplex virus type 1 involves the activity of viral fusion proteins

    Herpesvirus infection reorganizes components of the nuclear lamina usually without loss of integrity of the nuclear membranes. We report that wild-type HSV infection can cause dissolution of the nuclear envelope in transformed mouse embryonic fibroblasts that do not express torsinA. Nuclear envelope breakdown is accompanied by an eight-fold inhibition of virus replication. Breakdown of the membrane is much more limited during infection with viruses that lack the gB and gH genes, suggesting that breakdown involves factors that promote fusion at the nuclear membrane. Nuclear envelope breakdown is also inhibited during infection with virus that does not express UL34, but is enhanced when the US3 gene is deleted, suggesting that envelope breakdown may be enhanced by nuclear lamina disruption. Nuclear envelope breakdown cannot compensate for deletion of the UL34 gene suggesting that mixing of nuclear and cytoplasmic contents is insufficient to bypass loss of the normal nuclear egress pathway. - Highlights: • We show that wild-type HSV can induce breakdown of the nuclear envelope in a specific cell system. • The viral fusion proteins gB and gH are required for induction of nuclear envelope breakdown. • Nuclear envelope breakdown cannot compensate for deletion of the HSV UL34 gene

  1. Nuclear envelope breakdown induced by herpes simplex virus type 1 involves the activity of viral fusion proteins

    Maric, Martina; Haugo, Alison C. [Department of Microbiology, University of Iowa, Iowa City, IA 52242 (United States); Dauer, William [Department of Neurology, University of Michigan, Ann Arbor, MI 48109 (United States); Johnson, David [Department of Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201 (United States); Roller, Richard J., E-mail: richard-roller@uiowa.edu [Department of Microbiology, University of Iowa, Iowa City, IA 52242 (United States)

    2014-07-15

    Herpesvirus infection reorganizes components of the nuclear lamina usually without loss of integrity of the nuclear membranes. We report that wild-type HSV infection can cause dissolution of the nuclear envelope in transformed mouse embryonic fibroblasts that do not express torsinA. Nuclear envelope breakdown is accompanied by an eight-fold inhibition of virus replication. Breakdown of the membrane is much more limited during infection with viruses that lack the gB and gH genes, suggesting that breakdown involves factors that promote fusion at the nuclear membrane. Nuclear envelope breakdown is also inhibited during infection with virus that does not express UL34, but is enhanced when the US3 gene is deleted, suggesting that envelope breakdown may be enhanced by nuclear lamina disruption. Nuclear envelope breakdown cannot compensate for deletion of the UL34 gene suggesting that mixing of nuclear and cytoplasmic contents is insufficient to bypass loss of the normal nuclear egress pathway. - Highlights: • We show that wild-type HSV can induce breakdown of the nuclear envelope in a specific cell system. • The viral fusion proteins gB and gH are required for induction of nuclear envelope breakdown. • Nuclear envelope breakdown cannot compensate for deletion of the HSV UL34 gene.

  2. High-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of corticotropin-releasing factor and its type-1 receptors

    Xue-qun CHEN; Fan-ping KONG; Yang ZHAO; Ji-zeng DU

    2012-01-01

    High-altitude hypoxia can induce physiological dysfunction and mountain sickness,but the underlying mechanism is not fully understood.Corticotrophin-releasing factor (CRF) and CRF type-1 receptors (CRFR1) are members of the CRF family and the essential controllers of the physiological activity of the hypothalamo-pituitary-adrenal (HPA) axis and modulators of endocrine and behavioral activity in response to various stressors.We have previously found that high-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of CRF and CRFR1 in the brain and periphery that include activation of the HPA axis in a time-and dose-dependent manner,impaired or improved learning and memory,and anxiety-like behavioral change.Meanwhile,hypoxia induces dysfunctions of the hypothalamo-pituitary-endocrine and immune systems,including suppression of growth and development,as well as inhibition of reproductive,metabolic and immune functions.In contrast,the small mammals that live on the Qinghai-Tibet Plateau alpine meadow display low responsiveness to extreme high-altitudehypoxia challenge,suggesting well-acclimatized genes and a physiological strategy that developed during evolution through interact-ions between the genes and environment.All the findings provide evidence for understanding the neuroendocrine mechanisms of hypoxia-induced physiological dysfunction.This review extends these findings.

  3. The Pseudomonas aeruginosa Type VI Secretion PGAP1-like Effector Induces Host Autophagy by Activating Endoplasmic Reticulum Stress.

    Jiang, Feng; Wang, Xia; Wang, Bei; Chen, Lihong; Zhao, Zhendong; Waterfield, Nicholas R; Yang, Guowei; Jin, Qi

    2016-08-01

    Pseudomonas aeruginosa is an opportunistic pathogen that regularly causes nosocomial infections in hospitalized patients. The type VI secretion system (T6SS) is responsible for the secretion of numerous virulence effector proteins that can both interfere with competing microbes and manipulate host cells. Here, we report a detailed investigation of a P. aeruginosa H2-T6SS-dependent phospholipase effector, TplE, which acts as a trans-kingdom toxin. Delivery of TplE to the periplasmic space of rival bacteria leads to growth inhibition. Importantly, TplE, also contains a eukaryotic PGAP1-like domain, which targets the host ER apparatus, ultimately leading to disruption of the ER. TplE activity leads to the activation of the unfolded protein response (UPR) through the IRE1α-XBP1 pathway, enhancing autophagic flux. These findings indicate that this T6SS-delivered phospholipase effector is active against both prokaryotic and eukaryotic cellular targets, highlighting the T6SS as a versatile weapon in the Pseudomonas arsenal. PMID:27477276

  4. Biological Activities of Chinese Propolis and Brazilian Propolis on Streptozotocin-Induced Type 1 Diabetes Mellitus in Rats

    Zhu, Wei; Chen, Minli; Shou, Qiyang; Li, Yinghua; Hu, Fuliang

    2011-01-01

    Propolis is a bee-collected natural product and has been proven to have various bioactivities. This study tested the effects of Chinese propolis and Brazilian propolis on streptozotocin-induced type 1 diabetes mellitus in Sprague-Dawley rats. The results showed that Chinese propolis and Brazilian propolis significantly inhibited body weight loss and blood glucose increase in diabetic rats. In addition, Chinese propolis-treated rats showed an 8.4% reduction of glycated hemoglobin levels compared with untreated diabetic rats. Measurement of blood lipid metabolism showed dyslipidemia in diabetic rats and Chinese propolis helped to reduce total cholesterol level by 16.6%. Moreover, oxidative stress in blood, liver and kidney was improved to various degrees by both Chinese propolis and Brazilian propolis. An apparent reduction in levels of alanine transaminase, aspartate transaminase, blood urea nitrogen and urine microalbuminuria-excretion rate demonstrated the beneficial effects of propolis in hepatorenal function. All these results suggested that Chinese propolis and Brazilian propolis can alleviate symptoms of diabetes mellitus in rats and these effects may partially be due to their antioxidant ability. PMID:21785625

  5. Biological Activities of Chinese Propolis and Brazilian Propolis on Streptozotocin-Induced Type 1 Diabetes Mellitus in Rats

    Wei Zhu

    2011-01-01

    Full Text Available Propolis is a bee-collected natural product and has been proven to have various bioactivities. This study tested the effects of Chinese propolis and Brazilian propolis on streptozotocin-induced type 1 diabetes mellitus in Sprague-Dawley rats. The results showed that Chinese propolis and Brazilian propolis significantly inhibited body weight loss and blood glucose increase in diabetic rats. In addition, Chinese propolis-treated rats showed an 8.4% reduction of glycated hemoglobin levels compared with untreated diabetic rats. Measurement of blood lipid metabolism showed dyslipidemia in diabetic rats and Chinese propolis helped to reduce total cholesterol level by 16.6%. Moreover, oxidative stress in blood, liver and kidney was improved to various degrees by both Chinese propolis and Brazilian propolis. An apparent reduction in levels of alanine transaminase, aspartate transaminase, blood urea nitrogen and urine microalbuminuria-excretion rate demonstrated the beneficial effects of propolis in hepatorenal function. All these results suggested that Chinese propolis and Brazilian propolis can alleviate symptoms of diabetes mellitus in rats and these effects may partially be due to their antioxidant ability.

  6. Wild-Type N-Ras, Overexpressed in Basal-like Breast Cancer, Promotes Tumor Formation by Inducing IL-8 Secretion via JAK2 Activation

    Ze-Yi Zheng

    2015-07-01

    Full Text Available Basal-like breast cancers (BLBCs are aggressive, and their drivers are unclear. We have found that wild-type N-RAS is overexpressed in BLBCs but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, whereas overexpression enhances these processes even in preinvasive BLBC cells. We identified N-Ras-responsive genes, most of which encode chemokines; e.g., IL8. Expression levels of these chemokines and N-RAS in tumors correlate with outcome. N-Ras, but not K-Ras, induces IL-8 by binding and activating the cytoplasmic pool of JAK2; IL-8 then acts on both the cancer cells and stromal fibroblasts. Thus, BLBC progression is promoted by increasing activities of wild-type N-Ras, which mediates autocrine/paracrine signaling that can influence both cancer and stroma cells.

  7. Camptothecin induces urokinase-type plasminogen activator gene-expression in human RC-K8 malignant lymphoma and H69 small cell lung cancer cells.

    Shibakura M

    2002-10-01

    Full Text Available We previously reported that anthracyclines, which could generate reactive oxygen species (ROS, could induce the urokinase-type plasminogen activator (uPA gene expression in human RC-K8 malignant lymphoma cells and in H69 small cell lung cancer (SCLC cells. In screening other uPA-inducible anti-cancer agents, we found that camptothecin (CPT and its derivative, SN38, could induce uPA in RC-K8 and H69 cells. CPT and SN38, which are also used for the treatment of lymphoma and SCLC, significantly increased the uPA accumulation in the conditioned media of both cells in a dose-dependent manner. The maximum induction of uPA mRNA levels was observed 24 h after stimulation. Pretreatment with pyrrolidine dithiocarbamate (PDTC, an anti-oxidant, inhibited the CPT-induced uPA mRNA expression. Thus, CPT induces uPA through gene expression, and, therefore, CPT may influence the tumor-cell biology by up-regulating the uPA/plasmin system.

  8. Southern copperhead venom enhances tissue-type plasminogen activator induced fibrinolysis but does not directly lyse human plasma thrombi.

    Nielsen, Vance G

    2016-07-01

    In addition to degrading fibrinogen as a source of consumptive coagulopathy, purified fractions of southern copperhead (Agkistrodon contortrix contortrix; A. c. contortrix) venom has been demonstrated to enhance fibrinolysis. The goal of this investigation was to characterize the kinetic fibrinolytic profile of A. c. contortrix venom in the absence and presence of tissue-type plasminogen activator (tPA) to determine if intact venom had tPA independent fibrinolytic properties. Utilizing thrombelastographic methods, the coagulation and fibrinolytic kinetic profiles of human plasma exposed to A. c. contortrix venom (0-6 μg/ml) were determined in the absence or presence of tPA (0-100 IU/ml). Then, plasma was exposed to 0-6 μg/ml of venom without tPA added and coagulation observed for 3 h. Venom significantly prolonged the onset of coagulation, decreased the velocity of thrombus growth but did not significantly decrease clot strength. In the presence of tPA, venom significantly decreased clot strength, shortened the time of onset of fibrinolysis, decreased clot lysis time but did not significantly affect the maximum rate of lysis. Lastly, while venom exposure in the absence of tPA significantly prolonged the onset of coagulation and decreased the velocity of clot growth, venom exposure did not result in detectable fibrinolysis over the 3 h observation period. A. c. contortrix venom enhances tPA mediated fibrinolysis by degrading plasma coagulation kinetics. Intact A. c. contortrix venom does not possess sufficient fibrinolytic activity to cause fibrinolysis in human plasma at the concentration tested. PMID:26407681

  9. Isolation and Characterization of Dammarane-Type Saponins from Gynostemma pentaphyllum and Their Inhibitory Effects on IL-6-Induced STAT3 Activation.

    Lee, Chul; Lee, Jin Woo; Jin, Qinghao; Jang, Hari; Jang, Hyun-Jae; Rho, Mun-Chual; Lee, Myung Koo; Lee, Chong Kil; Lee, Mi Kyeong; Hwang, Bang Yeon

    2015-05-22

    Five new dammarane-type saponins, gypenosides GD1-GD5 (1-5), along with six known saponins (6-11), were isolated from the aerial parts of Gynostemma pentaphyllum using various chromatographic methods. Their structures were elucidated by a combination of spectroscopic and spectrometric data, including 1D and 2D NMR and HRESIMS. All isolates were tested for their inhibitory effects on IL-6-induced STAT3 promoter activity in Hep3B cells. Compounds 1, 9, and 11 displayed potent inhibitory effects, with IC50 values ranging from 0.27 to 0.59 μM. PMID:25895106

  10. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Watanabe, Tatsuo [Laboratory of Food Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Imai, Yasuyuki, E-mail: imai@u-shizuoka-ken.ac.jp [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan)

    2012-11-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  11. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  12. Influence of inducible cross-resistance to macrolides, lincosamides, and streptogramin B-type antibiotics in Enterococcus faecium on activity of quinupristin-dalfopristin in vitro and in rabbits with experimental endocarditis.

    Fantin, B.; Leclercq, R.; Garry, L; Carbon, C

    1997-01-01

    The influence of inducible cross-resistance to macrolides, lincosamides, and streptogramin B (MLS(B)) type antibiotics (inducible MLS(B) phenotype) on the activity of quinupristin-dalfopristin was investigated against Enterococcus faecium in vitro and in rabbits with experimental endocarditis. In vitro, quinupristin-dalfopristin displayed bacteriostatic and bactericidal activities against a MLS(B)-susceptible strain similar to those against two strains with the inducible MLS(B) phenotype. In ...

  13. Coriander leaf extract exerts antioxidant activity and protects against UVB-induced photoaging of skin by regulation of procollagen type I and MMP-1 expression.

    Hwang, Eunson; Lee, Do-Gyeong; Park, Sin Hee; Oh, Myung Sook; Kim, Sun Yeou

    2014-09-01

    Ultraviolet (UV) radiation causes photodamage to the skin, which, in turn, leads to depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkles are associated with collagen synthesis and matrix metalloproteinase-1 (MMP-1) activity. Coriandrum sativum L. (coriander leaf, cilantro; CS) has been used as a herbal medicine for the treatment of diabetes, hyperlipidemia, liver disease, and cancer. In this study, we examined whether CS ethanol extract (CSE) has protective effects against UVB-induced skin photoaging in normal human dermal fibroblasts (NHDF) in vitro and in the skin of hairless mice in vivo. The main component of CSE, linolenic acid, was determined by gas chromatography-mass spectroscopy. We measured the cellular levels of procollagen type I and MMP-1 using ELISA in NHDF cells after UVB irradiation. NHDF cells that were treated with CSE after UVB irradiation exhibited higher procollagen type I production and lower levels of MMP-1 than untreated cells. We found that the activity of transcription factor activator protein-1 (AP-1) was also inhibited by CSE treatment. We measured the epidermal thickness, dermal collagen fiber density, and procollagen type I and MMP-1 levels in photo-aged mouse skin in vivo using histological staining and western blot analysis. Our results showed that CSE-treated mice had thinner epidermal layers and denser dermal collagen fibers than untreated mice. On a molecular level, it was further confirmed that CSE-treated mice had lower MMP-1 levels and higher procollagen type I levels than untreated mice. Our results support the potential of C. sativum L. to prevent skin photoaging. PMID:25019675

  14. A peptide tetramer Tk-tPN induces tolerance of cardiac allografting by conversion of type 1 to type 2 immune responses via the Toll-like receptor 2 signal-promoted activation of the MCP1 gene.

    Li, Zuoqing; Yang, Neng; Zhou, Ling; Gu, Peng; Wang, Hui; Zhou, Yun; Zhou, Peijun; Lu, Liming; Chou, Kuang-Yen

    2016-03-01

    The plant protein trichosanthin (Tk) and its derived peptide tetramer Tk-tPN have been shown to stimulate the type 2 immune responses for treating autoimmune disease. This work explores the possibility of using Tk-tPN as a non-toxic immunosuppressant to induce transplantation tolerance using the mechanisms by which T-cell-mediated immune responses are transferred from type 1 to type 2 through innate immunity-related pathways. Immunocytes and cytokine secretions involved in the mouse cardiac allografting model with Tk-tPN treatment were characterized. Identification of critical genes and analysis of their functions through Toll-like receptor (TLR) -initiated signalling and the possible epigenetic changes were performed. Mean survival times of the cardiac allografts were delayed from 7·7 ± 0·3 days (control) to 22·7 ± 3·9 days (P Gata3(+) ), together with a selective expansion of the IL-4/IL-10-producing CD8(+)  CD28(-) regulatory T-cell subset. A TLR2-initiated high expression of chemokine gene MCP1 was detectable simultaneously. Epigenetically Tk/Tk-tPN could also acetylate the histone H3K9 of MCP1 promoter to skew the immunity towards T helper type 2 responses. Tk/Tk-tPN is therefore capable of down-regulating the type 1 response-dominant rejection of cardiac allografts by evoking type 2 immunity through the activation of a TLR2-initiated signalling pathway and MCP1 gene to expand the IL-4/IL-10-secreting CD8(+)  CD28(-) regulatory T cells. Tk-tPN could be a promising novel immunosuppressant to induce tolerance in allotransplantation. PMID:26694804

  15. Irradiation-Induced Regulation of Plasminogen Activator Inhibitor Type-1 and Vascular Endothelial Growth Factor in Six Human Squamous Cell Carcinoma Lines of the Head and Neck

    Purpose: It has been shown that plasminogen activator inhibitor type-1 (PAI-1) and vascular endothelial growth factor (VEGF) are involved in neo-angiogenesis. The aim of this study was to investigate the irradiation-induced regulation of PAI-1 and VEGF in squamous cell carcinomas of the head and neck (SCCHN) cell lines of varying radiation sensitivity. Methods and Materials: Six cell lines derived from SCCHN were investigated in vitro. The colorimetric AlamarBlue assay was used to detect metabolic activity of cell lines during irradiation as a surrogate marker for radiation sensitivity. PAI-1 and VEGF secretion levels were measured by enzyme-linked immunosorbent assay 24, 48, and 72 h after irradiation with 0, 2, 6, and 10 Gy. The direct radioprotective effect of exogenous PAI-1 was measured using the clonogenic assay. For regulation studies, transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), or both HIF-1α and HIF-2α were downregulated using siRNA. Results: Although baseline levels varied greatly, irradiation led to a comparable dose-dependent increase in PAI-1 and VEGF secretion in all six cell lines. Addition of exogenous stable PAI-1 to the low PAI-1-expressing cell lines, XF354 and FaDu, did not lead to a radioprotective effect. Downregulation of TGF-β1 significantly decreased VEGF secretion in radiation-sensitive XF354 cells, and downregulation of HIF-1α and HIF-2α reduced PAI-1 and VEGF secretion in radiation-resistant SAS cells. Conclusions: Irradiation dose-dependently increased PAI-1 and VEGF secretion in all SCCHN cell lines tested regardless of their basal levels and radiation sensitivity. In addition, TGF-β1 and HIF-1α could be partly responsible for VEGF and PAI-1 upregulation after irradiation.

  16. Whence Induced Demand: How Access Affects Activity

    Levinson, David; Kanchi, Seshasai

    2000-01-01

    Additional highway capacity, by increasing travel speed, affects the individual share of time within a 24-hour budget allocated to various activities (time spent at and traveling to home, shop, work and other), some activities will be undertaken more, others less. This paper extends previous research that identified and quantified induced demand in terms of vehicle miles traveled, by considering questions of what type of demand is induced and which activities are consequently reduced. This pa...

  17. Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

    Yogi, Alvaro; Callera, Glaucia E. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Mecawi, André S. [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Batalhão, Marcelo E.; Carnio, Evelin C. [Department of General and Specialized Nursing, College of Nursing of Ribeirão Preto, USP, São Paulo (Brazil); Antunes-Rodrigues, José [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Queiroz, Regina H. [Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences, USP, São Paulo (Brazil); Touyz, Rhian M. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br [Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP (Brazil)

    2012-11-01

    Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin–angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective AT{sub 1} receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P)H oxidase‐mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT{sub 1}-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ► Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ► RAS plays a role in acute ethanol-induced oxidative damage via AT{sub 1} receptor activation.

  18. Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

    Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin–angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective AT1 receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P)H oxidase‐mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT1-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ► Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ► RAS plays a role in acute ethanol-induced oxidative damage via AT1 receptor activation. ► Translocation of p47

  19. Type analysis mining induced tremors

    Buben, Jiří; Vencovský, Miloš; Klos, Pavel

    2000-01-01

    Roč. 2000, 16 (118) (2000), s. 33-43. ISSN 1211-1910 Institutional research plan: CEZ:AV0Z3046908 Keywords : rockburst * cross correlation * type analysis Subject RIV: DC - Siesmology, Volcanology, Earth Structure

  20. Inducible ASABF-Type Antimicrobial Peptide from the Sponge Suberites domuncula: Microbicidal and Hemolytic Activity in Vitro and Toxic Effect on Molluscs in Vivo

    Werner E. G. Müller

    2011-10-01

    Full Text Available Since sponges, as typical filter-feeders, are exposed to a high load of attacking prokaryotic and eukaryotic organisms, they are armed with a wide arsenal of antimicrobial/cytostatic low-molecular-weight, non-proteinaceous bioactive compounds. Here we present the first sponge agent belonging to the group of ASABF-type antimicrobial peptides. The ASABF gene was identified and cloned from the demospongeSuberites domuncula. The mature peptide, with a length of 64 aa residues has a predicted pI of 9.24, and comprises the characteristic CSαβ structural motif. Consequently, the S. domuncula ASABF shares high similarity with the nematode ASABFs; it is distantly related to the defensins. The recombinant peptide was found to display besides microbicidal activity, anti-fungal activity. In addition, the peptide lyses human erythrocytes. The expression ofASABF is upregulated after exposure to the apoptosis-inducing agent 2,2'-dipyridyl. During the process of apoptosis of surface tissue of S. domuncula, grazing gastropods (Bittium sp. are attracted by quinolinic acid which is synthesized through the kynurenine pathway by the enzyme 3-hydroxyanthranilate 3,4-dioxygenase (HAD. Finally, the gastropods are repelled from the sponge tissue by the ASABF. It is shown that the effector peptide ASABF is sequentially expressed after the induction of the HAD gene and a caspase, as a central enzyme executing apoptosis.

  1. Berberine treatment prevents cardiac dysfunction and remodeling through activation of 5'-adenosine monophosphate-activated protein kinase in type 2 diabetic rats and in palmitate-induced hypertrophic H9c2 cells.

    Chang, Wenguang; Zhang, Ming; Meng, Zhaojie; Yu, Yang; Yao, Fan; Hatch, Grant M; Chen, Li

    2015-12-15

    Diabetic cardiomyopathy is the major cause of death in type 2 diabetic patients. Berberine is an isoquinoline alkaloid extract from traditional chinese herbs and its hypoglycemic and hypolipidemic effects make it a promising drug for treatment of type 2 diabetes. We examined if berberine improved cardiac function and attenuated cardiac hypertrophy and fibrosis in high fat diet and streptozotocin induced-type 2 diabetic rats in vivo and reduced expression of hypertrophy markers in palmitate-induced hypertrophic H9c2 cells in vitro. Treatment of diabetic animals with berberine partially improved cardiac function and restored fasting blood insulin, fasting blood glucose, total cholesterol, and triglyceride levels to that of control. In addition, berberine treatment of diabetic animals increased cardiac 5'-adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (AKT) activation and reduced glycogen synthase kinase 3 beta (GSK3β) activation compared to control. Palmitate incubation of H9c2 cells resulted in cellular hypertrophy and decreased expression of alpha-myosin heavy chain (α-MHC) and increased expression of beta-myosin heavy chain (β-MHC) compared to controls. Berberine treatment of palmitate-incubated H9c2 cells reduced hypertrophy, increased α-MHC expression and decreased β-MHC expression. In addition, berberine treatment of palmitate-incubated H9c2 cells increased AMPK and AKT activation and reduced GSK3β activation. The presence of the AMPK inhibitor Compound C attenuated the effects of berberine. The results strongly indicate that berberine treatment may be protective against the development of diabetic cardiomyopathy. PMID:26522928

  2. Exercise-induced oxidative stress and antioxidant enzyme activity in type 2 diabetic patients with and without diastolic dysfunction and hypertension

    Kostić Nada

    2009-01-01

    increase of GSH-Px activity (47.10±7.37 vs 54.52±11.97 U/g Hb; p<0.01. Conclusion. Elevated enzyme levels are associated with exercise in type 2 diabetic patients. We suggest that it could be a compensatory mechanism to prevent free radical tissue damage. We hypothesize that a physical training programme induces the enhancement of muscular and liver antioxidant enzymes and reduces the oxidative stress.

  3. Cancer-induced Expansion and Activation of CD11b(+)Gr-1(+) Cells Predispose Mice to Adenoviral-triggered Anaphylactoid-type Reactions

    Pande, K.; Ueda, R.; Machemer, T.; Sathe, M.; Tsai, V.; Brin, E.; Delano, M.J.; Rooijen, van N.; McClanahan, T.K.; Talmadge, J.E.; Moldawer, L.L.; Phillips, J.R.; Laface, D.M.

    2009-01-01

    Intravascular delivery (1.5 x 10(9) particles and higher) of recombinant adenovirus (rAd) induces myeloid cell mediated, self-limiting hemodynamic responses in normal mice. However, we observed anaphylactoid-type reactions and exacerbated hemodynamic events following rAd injection in mice bearing ma

  4. Cancer-induced bone pain sequentially activates the ERK/MAPK pathway in different cell types in the rat spinal cord

    Cheng Hao; Ji Fu-hai; Zhang Yan-bing; Li Cai-fang; Peng Yan; Peng Jun; Yang Jian-ping; Yao Ming; Wang Li-na; Xu Qi-nian; Wang Xiu-yun; Zuo Jian-ling

    2011-01-01

    Abstract Background Previous studies have demonstrates that, after nerve injury, extracellular signal-regulated protein kinase (ERK) activation in the spinal cord-initially in neurons, then microglia, and finally astrocytes. In addition, phosphorylation of ERK (p-ERK) contributes to nociceptive responses following inflammation and/or nerve injury. However, the role of spinal cells and the ERK/MAPK pathway in cancer-induced bone pain (CIBP) remains poorly understood. The present study analyzed...

  5. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Jun Liu

    2011-03-01

    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  6. The types and characteristics of man-induced sediment disaster

    2002-01-01

    The man-induced sediment disaster includes material erosion, transportation and accumula-tion by human activities. It possesses special attribute in sociology and disaster science. In accordancewith human activities, geomorphologic location, behavior and particular, the man-induced sedimentdisaster can be divided into 4 types: the drainage network, slope and gully, channel and plain-estu-au-coastline. Each type includes erosion, transportation, accumulation, complexity and cascading.Based on human activity, geomorphology, sediment mechanics and catastrophology, the man-inducedsediment disaster is characterized as follows: (1) accelerating tendency with geographical zoning back-ground; (2) non-order characters by blind action without special technical training; (3) gradually andsharply changing with human environment vibration; and (4) complexity and non-linear figure, etc.One of the reasons leading to man-induced sediment disaster is human environment vibration.

  7. C-type lectin receptor dectin-3 mediates trehalose 6,6'-dimycolate (TDM)-induced Mincle expression through CARD9/Bcl10/MALT1-dependent nuclear factor (NF)-κB activation.

    Zhao, Xue-Qiang; Zhu, Le-Le; Chang, Qing; Jiang, Changying; You, Yun; Luo, Tianming; Jia, Xin-Ming; Lin, Xin

    2014-10-24

    Previous studies indicate that both Dectin-3 (also called MCL or Clec4d) and Mincle (also called Clec4e), two C-type lectin receptors, can recognize trehalose 6,6'-dimycolate (TDM), a cell wall component from mycobacteria, and induce potent innate immune responses. Interestingly, stimulation of Dectin-3 by TDM can also induce Mincle expression, which may enhance the host innate immune system to sense Mycobacterium infection. However, the mechanism by which Dectin-3 induces Mincle expression is not fully defined. Here, we show that TDM-induced Mincle expression is dependent on Dectin-3-mediated NF-κB, but not nuclear factor of activated T-cells (NFAT), activation, and Dectin-3 induces NF-κB activation through the CARD9-BCL10-MALT1 complex. We found that bone marrow-derived macrophages from Dectin-3-deficient mice were severely defective in the induction of Mincle expression in response to TDM stimulation. This defect is correlated with the failure of TDM-induced NF-κB activation in Dectin-3-deficient bone marrow-derived macrophages. Consistently, inhibition of NF-κB, but not NFAT, impaired TDM-induced Mincle expression, whereas NF-κB, but not NFAT, binds to the Mincle promoter. Dectin-3-mediated NF-κB activation is dependent on the CARD9-Bcl10-MALT1 complex. Finally, mice deficient for Dectin-3 or CARD9 produced much less proinflammatory cytokines and keyhole limpet hemocyanin (KLH)-specific antibodies after immunization with an adjuvant containing TDM. Overall, this study provides the mechanism by which Dectin-3 induces Mincle expression in response to Mycobacterium infection, which will have significant impact to improve adjuvant and design vaccine for antimicrobial infection. PMID:25202022

  8. Interleukin-1ß-induced expression of the urokinase-type plasminogen activator receptor and its co-localization with MMPs in human articular chondrocytes

    Schwab, W.; Schulze-Tanzil, G.; Mobasheri, A; Dressler, J.; Kotzsch, M.; Shakibaei, M.

    2004-01-01

    The urokinase-type plasminogen activator receptor (uPAR) plays a critical role in cartilage degradation during osteoarthritis as it regulates pericellular proteolysis mediated by serine proteinases. Another important family of proteinases responsible for ECM destruction in arthritis are the matrix metalloproteinases (MMPs). MMPs are regulated by IL- 1ß, a cytokine that plays a pivotal role in pathogenesis of osteoarthritis. This study was undertaken to address ...

  9. High glucose and hyperglycemic sera from type 2 diabetic patients impair DC differentiation by inducing ROS and activating Wnt/β-catenin and p38 MAPK.

    Gilardini Montani, Maria Saveria; Granato, Marisa; Cuomo, Laura; Valia, Sandro; Di Renzo, Livia; D'Orazi, Gabriella; Faggioni, Alberto; Cirone, Mara

    2016-04-01

    Type 2 is the type of diabetes with higher prevalence in contemporary time, representing about 90% of the global cases of diabetes. In the course of diabetes, several complications can occur, mostly due to hyperglycemia and increased reactive oxygen species (ROS) production. One of them is represented by an increased susceptibility to microbial infections and by a reduced capacity to clear them. Therefore, knowing the impact of hyperglycemia on immune system functionality is of utmost importance for the management of the disease. In this study, we show that medium containing high glucose reduced the in-vitro differentiation of monocytes into functional DCs and their activation mediated by PAMPs or DAMPs. Most importantly, the same effects were mediated by the hyperglycemic sera derived by type 2 diabetic patients, mimicking a more physiologic condition. DC dysfunction caused by hyperglycemia may be involved in the inefficient control of infections observed in diabetic patients, given the pivotal role of these cells in both the innate and adaptive immune response. Searching for the molecular mechanisms underlying DC dysfunction, we found that canonical Wnt/β-catenin and p38 MAPK pathways were activated in the DCs differentiated either in the presence of high glucose or of hyper-glycemic sera. Interestingly, the activation of these pathways and the DC immune dysfunction were partially counteracted by the anti-oxidant quercetin, a flavonoid already known to exert several beneficial effects in diabetes. PMID:26769359

  10. Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia of Cordyceps militaris in High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice

    Sung-Hsun Yu

    2015-01-01

    Full Text Available Diabetes mellitus (DM is currently ranked among leading causes of death worldwide in which type 2 DM is reaching an epidemic proportion. Hypoglycemic medications for type 2 DM have either proven inadequate or posed adverse effects; therefore, the Chinese herbal products are under investigation as an alternative treatment. In this study, a novel combination of fruiting body and mycelia powder of herbal Cordyceps militaris number 1 (CmNo1 was administered to evaluate their potential hypoglycemic effects in high-fat diet- (HFD- induced type 2 DM in C57BL/6J mice. Body weight, fasting blood glucose (FBG, oral glucose tolerance test (OGTT, and blood biochemistry indexes were measured. Results indicated that CmNo1 lowered the blood glucose level by increasing insulin sensitivity, while no change in body weight was observed. Increased protein expression of IRS-1, pIRS-1, AKT, pAKT, and GLUT-4 in skeletal muscle and adipose tissue was found indicating restoration of insulin signaling. Additionally, PPAR-γ expression in adipose tissue restored the triglyceride and cholesterol levels. Finally, our results suggest that CmNo1 possesses strong hypoglycemic, anticholesterolemic, and antihypertriglyceridemic actions and is more economical alternate for DM treatment.

  11. Pharmacologically induced long QT type 2 can be rescued by activation of IKs with benzodiazepine R-L3 in isolated guinea pig cardiomyocytes

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

    2009-01-01

    The ionic current responsible for terminating the action potential (AP), and thereby in part determining the AP duration (APD), is the potassium current (IK), consisting of primarily two components: a rapidly (IKr) and a slowly (IKs) activating delayed rectifier potassium current. The aim of this...... study was to evaluate potential antiarrhythmic effects of compound induced IKs activation using the benzodiazepine L-364,373 (R-L3). Ventricular myocytes from guinea pigs were isolated and whole-cell current clamping was performed at 35 degrees C. It was found that 1 microM R-L3 significantly reduced...... increase in repolarizing capacity was seen with 1 microM R-L3, as more complete repolarization of the AP was achieved before EADs could be elicited. Finally, a functional demonstration of the repolarization reserve revealed that increased IKs can counteract a pharmacologically reduced IKr. In conclusion...

  12. Equid herpesvirus type 1 activates platelets.

    Tracy Stokol

    Full Text Available Equid herpesvirus type 1 (EHV-1 causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression and platelet microvesiculation (increased small events double positive for CD41 and Annexin V. Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM. A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis

  13. Cisplatin-induced apoptosis in non-small-cell lung cancer cells is dependent on Bax- and Bak-induction pathway and synergistically activated by BH3-mimetic ABT-263 in p53 wild-type and mutant cells.

    Matsumoto, Masaru; Nakajima, Wataru; Seike, Masahiro; Gemma, Akihiko; Tanaka, Nobuyuki

    2016-04-29

    Cisplatin is a highly effective anticancer drug for treatment of various tumors including non-small-cell lung cancer (NSCLC), and is especially useful in cases nonresponsive to molecular-targeted drugs. Accumulating evidence has shown that cisplatin activates the p53-dependent apoptotic pathway, but it also induces apoptosis in p53-mutated cancer cells. Here we demonstrated that DNA-damage inducible proapoptotic BH3 (Bcl-2 homology region 3)-only Bcl-2 family members, Noxa, Puma, Bim and Bid, are not involved in cisplatin-induced apoptosis in human NSCLC cell lines. In contrast, the expression of proapoptotic multidomain Bcl-2-family members, Bak and Bax, was induced by cisplatin in p53-dependent and -independent manners, respectively. Moreover, in wild-type p53-expressing cells, cisplatin mainly used the Bak-dependent apoptotic pathway, but this apoptotic pathway shifted to the Bax-dependent pathway by loss-of-function of p53. Furthermore, both Bak- and Bax-induced apoptosis was enhanced by the antiapoptotic Bcl-2 family member, Bcl-XL knockdown, but not by Mcl-1 knockdown. From this result, we tested the effect of ABT-263 (Navitoclax), the specific inhibitor of Bcl-2 and Bcl-XL, but not Mcl-1, and found that ABT-263 synergistically enhanced cisplatin-induced apoptosis in NSCLC cells in the presence or absence of p53. These results indicate a novel regulatory system in cisplatin-induced NSCLC cell apoptosis, and a candidate efficient combination chemotherapy method against lung cancers. PMID:26996126

  14. Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease.

    Toapanta, Franklin R; Bernal, Paula J; Fresnay, Stephanie; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

    2015-06-01

    A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD-) 5-10 days post-challenge. TD criteria included meeting clinical (oral temperature ≥38°C for ≥12 h) and/or microbiological (S. Typhi bacteremia) endpoints. One of the first lines of defense against pathogens are the cells of the innate immune system (e.g., monocytes, dendritic cells -DCs-). Various changes in circulating monocytes and DCs have been described in the murine S. Typhimurium model; however, whether similar changes are present in humans remains to be explored. To address these questions, a subset of volunteers (5 TD and 3 who did not develop typhoid despite oral challenge -NoTD-) were evaluated for changes in circulating monocytes and DCs. Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h). Moreover, integrin α4β7, a gut homing molecule, was upregulated on monocytes but not DCs. CD21 upregulation was only identified in DCs. These changes were not observed among NoTD volunteers despite the same oral challenge. Moreover, monocytes and DCs from NoTD volunteers showed increased binding to S. Typhi one day after challenge. These monocytes showed phosphorylation of p38MAPK, NFkB and Erk1/2 upon stimulation with S. Typhi-LPS-QDot micelles. In contrast, monocytes from TD volunteers showed only a moderate increase in S. Typhi binding 48 h and 96 h post-TD, and only Erk1/2 phosphorylation. This is the first study to describe different activation and migration profiles, as well as differential signaling patterns, in monocytes and DCs which relate directly to the clinical outcome following oral challenge with wild type S. Typhi. PMID:26065687

  15. In vitro inhibition activity of polyphenol-rich extracts from Syzygium aromaticum (L.) Merr. & Perry (Clove) buds against carbohydrate hydrolyzing enzymes linked to type 2 diabetes and Fe2+-induced lipid peroxidation in rat pancreas

    Stephen Adeniyi Adefegha; Ganiyu Oboh

    2012-01-01

    To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe2+-induced lipid peroxidation in rat pancreas in vitro. Methods: The free phenolics were extracted with 80% (v/v) acetone, while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Then, the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed. Thereafter, the total phenolic contents and antioxidant activities of the extracts were determined. Results: The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner. However, the alpha-glucosidase inhibitory activity of the extracts were significantly (P<0.05) higher than their alpha-amylase inhibitory activity. The free phenolics (31.67 mg/g) and flavonoid (17.28 mg/g) contents were significantly (P<0.05) higher than bound phenolic (23.52 mg/g) and flavonoid (13.70 mg/g) contents. Both extracts also exhibited high antioxidant activities as typified by their high reducing power, 1,1 diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate (ABTS) radical scavenging abilities, as well as inhibition of Fe2+-induced lipid peroxidation in rat pancreas in vitro. Conclusions: This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.

  16. Irradiation-induced regulation of plasminogen activator inhibitor type-1 and vascular endothelial growth factor in six human squamous cell carcinoma lines of the head and neck

    Radiation therapy is frequently used to treat squamous cell carcinoma of the head and neck (SCCHN), although, it can be unsuccessful due to radiation resistance of the tumor. Currently, there are no established predictive markers for radiation resistance in SCCHN. The aim of this work was to investigate PAI-1 and VEGF secretion as markers for radiation resistance in six human SCCHN cell lines. The cell lines differed in their basal secretion levels and in their in vitro radiation sensitivity. PAI-1 and VEGF levels increased after irradiation in a dose-dependent manner. A significant correlation was detected between radiation-induced PAI-1 and VEGF secretion, which suggests that irradiation-induced secretion of PAI-1 and VEGF are partially regulated by related mechanisms. However, neither basal levels nor radiation-induced PAI-1 and VEGF secretion correlated with radiation resistance. Therefore, PAI-1 and VEGF are most likely not predictive markers for radiation resistance in SCCHN.

  17. Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats

    Hardik Soni

    2014-01-01

    Full Text Available Background: Glucova Active Tablet is a proprietary Ayurvedic formulation with ingredients reported for anti-hyperglycemic, anti-hyperlipidemic activity and antioxidant properties. Objective: Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats. Materials and Methods: Experimental Type I diabetes was induced in 24 albino rats with intra-peritoneal injection of streptozotocin (50 mg/kg. Type II diabetes was induced in 18 albino rats by intra-peritoneal injection of streptozotocin (35 mg/kg along with high fat diet. The rats were divided in 5 groups for Type I model and 4 groups for Type II model. Normal control group was kept common for both experimental models. Glucova Active Tablet (108 mg/kg treatment was provided for 28 days twice daily orally. Fasting blood glucose level, serum lipid profile and liver anti-oxidant parameters like superoxide dismutase and reduced glutathione was carried out in both experimental models. Pancreas histopathology was also done. Statistical analysis were done by ′analysis of variance′ test followed by post hoc Tukey′s test, with significant level of P < 0.05.Results and Discussion: Glucova Active Tablet showed significant effect on fasting blood glucose level. It also showed significant alteration in lipid profile and antioxidant parameters. Histopathology study revealed restoration of beta cells in pancreas in Glucova Active Tablet treated group. Conclusion: Finding of this study concludes that Glucova Active Tablet has shown promising anti-diabetic activity in Type I and Type II diabetic rats. It was also found showing good anti-hyperlipidemic activity and anti-oxidant property.

  18. Domain-induced activation of human phospholipase A2 type IIA: Local versus global lipid composition

    Leidy, C.; Linderoth, L.; Andresen, T.L.; Mouritsen, O.G.; Jørgensen, K.; Peters, Günther H.j.

    2006-01-01

    , we show that local enrichment of anionic lipids into fluid domains triggers PLA(2)-IIA activity. In addition, the compositional range of enzyme activity is shown to be related to the underlying lipid phase diagram. A comparison is done between PLA(2)-IIA and snake venom PLA(2), which in contrast to...... PLA(2)-IIA hydrolyzes both anionic and zwitterionic membranes. In general, this work shows that PLA(2)-IIA activation can be accomplished through local enrichment of anionic lipids into domains, indicating a mechanism for PLA(2)-IIA to target perturbed native membranes with low global anionic lipid...... contents. The results also show that the underlying lipid phase diagram, which determines the lipid composition at a local level, can be used to predict PLA(2)-IIA activity....

  19. A novel mode of human immunodeficiency virus type 1 (HIV-1) activation: ligation of CD28 alone induces HIV-1 replication in naturally infected lymphocytes.

    1993-01-01

    Induction of human immunodeficiency virus (HIV) replication in infected CD4+ T lymphocytes requires cellular activation. The ligation of CD28, a signal-transducing receptor with a natural ligand on activated B cells and antigen-presenting cells, provides a costimulating signal for interleukin 2 production and T-cell proliferation as well as coactivation of the transfected HIV long terminal repeat in Jurkat cells. The aim of the present study was to investigate the ability of CD28 ligation to ...

  20. Chronic hypoxia induces the activation of the Wnt/β-catenin signaling pathway and stimulates hippocampal neurogenesis in wild-type and APPswe-PS1ΔE9 transgenic mice in vivo

    Varela-Nallar, Lorena; Rojas-Abalos, Macarena; Abbott, Ana C.; Moya, Esteban A.; Iturriaga, Rodrigo; Inestrosa, Nibaldo C.

    2014-01-01

    Hypoxia modulates proliferation and differentiation of cultured embryonic and adult stem cells, an effect that includes β-catenin, a key component of the canonical Wnt signaling pathway. Here we studied the effect of mild hypoxia on the activity of the Wnt/β-catenin signaling pathway in the hippocampus of adult mice in vivo. The hypoxia-inducible transcription factor-1α (HIF-1α) was analyzed as a molecular control of the physiological hypoxic response. Exposure to chronic hypoxia (10% oxygen for 6–72 h) stimulated the activation of the Wnt/β-catenin signaling pathway. Because the Wnt/β-catenin pathway is a positive modulator of adult neurogenesis, we evaluated whether chronic hypoxia was able to stimulate neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus. Results indicate that hypoxia increased cell proliferation and neurogenesis in adult wild-type mice as determined by Ki67 staining, Bromodeoxyuridine (BrdU) incorporation and double labeling with doublecortin (DCX). Chronic hypoxia also induced neurogenesis in a double transgenic APPswe-PS1ΔE9 mouse model of Alzheimer’s disease (AD), which shows decreased levels of neurogenesis in the SGZ. Our results show for the first time that exposure to hypoxia in vivo can induce the activation of the Wnt/β-catenin signaling cascade in the hippocampus, suggesting that mild hypoxia may have a therapeutic value in neurodegenerative disorders associated with altered Wnt signaling in the brain and also in pathological conditions in which hippocampal neurogenesis is impaired. PMID:24574965

  1. Coriander Leaf Extract Exerts Antioxidant Activity and Protects Against UVB-Induced Photoaging of Skin by Regulation of Procollagen Type I and MMP-1 Expression

    Hwang, Eunson; Lee, Do-Gyeong; Park, Sin Hee; Oh, Myung Sook; Kim, Sun Yeou

    2014-01-01

    Ultraviolet (UV) radiation causes photodamage to the skin, which, in turn, leads to depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkles are associated with collagen synthesis and matrix metalloproteinase-1 (MMP-1) activity. Coriandrum sativum L. (coriander leaf, cilantro; CS) has been used as a herbal medicine for the treatment of diabetes, hyperlipidemia, liver disease, and cancer. In this study, we examined whether CS ethanol extract (CSE) h...

  2. E6 and E7 oncoproteins from human papillomavirus type 16 induce activation of human transforming growth factor beta1 promoter throughout Sp1 recognition sequence.

    Peralta-Zaragoza, Oscar; Bermúdez-Morales, Víctor; Gutiérrez-Xicotencatl, Lourdes; Alcocer-González, Juan; Recillas-Targa, Félix; Madrid-Marina, Vicente

    2006-01-01

    Human Papillomavirus (HPV) infection is the main etiologic agent of cervical cancer and HPV E6 and E7 oncogenes trans-regulate many cellular genes. An association between TGF-beta1 gene expression and cervical cancer development has been suggested; however, the mechanisms by which HPV influences TGF-beta1 expression remain unclear. In the present study we analyzed the mechanism through which HPV-16 E6 and E7 oncoproteins regulate the TGF-beta1 promoter in cervical tumor cells. Our results showed that E6 and E7 increased TGF-beta1 promoter activity. Furthermore, we identified a specific DNA sequence motif in the TGF-beta1 core promoter that is responsible for trans-activation and that corresponds to the Sp1e-binding site associated with HPV-16 E6 and E7 oncoproteins. Mutational analysis showed that the Sp1e recognition site abolished the trans-activation caused by E6 and E7. These results suggest a physical interaction and functional cooperation between viral oncoproteins and cellular regulatory elements of the TGF-beta1 promoter, and may explain the contribution of HPV-16 to TGF-beta1 gene expression in cervical cancer. PMID:16987065

  3. In vitro inhibition activity of polyphenol-rich extracts from Syzygium aromaticum(L.)Merr.& Perry(Clove)buds against carbohydrate hydrolyzing enzymes linked to type 2 diabetes and Fe2+-induced lipid peroxidation in rat pancreas

    Stephen; Adeniyi; Adefegha; Ganiyu; Oboh

    2012-01-01

    Objective:To investigate and compare the inhibitor)’properties)of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes(alpha-amylase&alphaglucosidase)and Fe2+-induced lipid peroxidation in rat pancreas in vitro.Methods:The free phenolics were extracted with 80%.(v/v)acetone,while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate.Then,the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed.Thereafter,the total phenolic contents and antioxidant activities of the extracts were determined.Results:The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner.However,the alpha-glucosidase inhibitory activity of the extracts were significantly(P<0.05)higher than their alpha-amylase inhibitory activity.The free phenolics(31.67 mg/g)and flavonoid(17.28 mg/g)contents were significantly(P<0.05)higher than bound phenolic(23.52 mg/g)and flavonoid(13.70 mg/g)contents.Both extracts also exhibited high antioxidant activities as typified by their high reducing power,LI diphenyl-2-picrylhydrazyl(DPPH)and 2,2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate(ABTS)radical scavenging abilities,as well as inhibition of Fe2+-induced lipid peroxidation in rat pancreas in vitro.Conclusions:This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.

  4. Human immunodeficiency virus (HIV) type 1 Vpr induces differential regulation of T cell costimulatory molecules: Direct effect of Vpr on T cell activation and immune function

    Human immunodeficiency virus type 1 (HIV-1) viral proteins disrupt the normal host cellular immune pathways thus exploiting the cellular machinery for replication, survival and to escape host immune attack. Here we evaluated the direct effects of HIV-1 Vpr-mediated immune modulation of infected T cells. Vpr specifically downregulated the expression of CD28 and increased the expression of CTLA-4, whereas no significant difference in the expression of CD25 and HLA-DR was observed. Interferon gamma (IFN-γ) production in T cells was evaluated as a measure of the downstream effector functions. Results indicate that Vpr significantly inhibited IFN-γ production and this may, in part, due to Vpr's ability to inhibit the nuclear translocation of NF-κB, and its transcriptional regulation. Together these results support that HIV-1 Vpr selectively dysregulates the immune functions at multiple levels and exerts its inhibitory effects in the presence of other viral proteins

  5. 28-nor-oleanane-type triterpene saponins from Camellia japonica and their inhibitory activity on LPS-induced NO production in macrophage RAW264.7 cells.

    Thao, Nguyen Thi Phuong; Hung, Tran Manh; Cuong, To Dao; Kim, Jin Cheol; Kim, Eun Hee; Jin, Seong Eun; Na, MinKyun; Lee, Young Mi; Kim, Young Ho; Choi, Jae Sue; Min, Byung Sun

    2010-12-15

    Four new 28-nor-oleanane-type triterpene oligoglycosides, camellenodiol 3-O-β-D-galactopyranosyl(1→2)[β-D-xylopyranosyl(1→2)-β-D-galactopyranosyl(1→3)]-β-D-glucuronopyranoside (2), camellenodiol 3-O-4''-O-acetyl-β-D-galactopyranosyl(1→2)[β-D-xylopyranosyl(1→2)-β-D-galactopyranosyl(1→3)]-β-D-glucuronopyranoside (4), camellenodiol 3-O-(β-D-galactopyranosyl(1→2)[β-D-xylopyranosyl(1→2)-β-D-galactopyranosyl(1→3)]-6'-methoxy-β-D- glucuronopyranoside (5), and maragenin II 3-O-(β-D-galactopyranosyl(1→2)[β-D-xylopyranosyl(1→2)-β-D-galactopyranosyl(1→3)]-6'-methoxy-β-D-glucuronopyranoside (6), along with two known compounds, (1 and 3), were isolated from the stem bark of Camellia japonica. Their chemical structures were established mainly by 2D NMR techniques and mass spectrometry. The isolated compounds showed inhibitory effects on NO production in RAW264.7 macrophages. PMID:21050759

  6. Lipoteichoic acid induces surfactant protein-A biosynthesis in human alveolar type II epithelial cells through activating the MEK1/2-ERK1/2-NF-κB pathway

    Liu Feng-Lin

    2012-10-01

    Full Text Available Abstract Background Lipoteichoic acid (LTA, a gram-positive bacterial outer membrane component, can cause septic shock. Our previous studies showed that the gram-negative endotoxin, lipopolysaccharide (LPS, could induce surfactant protein-A (SP-A production in human alveolar epithelial (A549 cells. Objectives In this study, we further evaluated the effect of LTA on SP-A biosynthesis and its possible signal-transducing mechanisms. Methods A549 cells were exposed to LTA. Levels of SP-A, nuclear factor (NF-κB, extracellular signal-regulated kinase 1/2 (ERK1/2, and mitogen-activated/extracellular signal-regulated kinase kinase (MEK1 were determined. Results Exposure of A549 cells to 10, 30, and 50 μg/ml LTA for 24 h did not affect cell viability. Meanwhile, when exposed to 30 μg/ml LTA for 1, 6, and 24 h, the biosynthesis of SP-A mRNA and protein in A549 cells significantly increased. As to the mechanism, LTA enhanced cytosolic and nuclear NF-κB levels in time-dependent manners. Pretreatment with BAY 11–7082, an inhibitor of NF-κB activation, significantly inhibited LTA-induced SP-A mRNA expression. Sequentially, LTA time-dependently augmented phosphorylation of ERK1/2. In addition, levels of phosphorylated MEK1 were augmented following treatment with LTA. Conclusions Therefore, this study showed that LTA can increase SP-A synthesis in human alveolar type II epithelial cells through sequentially activating the MEK1-ERK1/2-NF-κB-dependent pathway.

  7. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis.

    Nathella Pavan Kumar

    Full Text Available BACKGROUND: Although Type 1 cytokine responses are considered protective in pulmonary tuberculosis (PTB, their role as well as those of Type 2, 17 and immunoregulatory cytokines in tuberculous lymphadenitis (TBL and latent tuberculosis (LTB have not been well studied. AIM AND METHODS: To identify cytokine responses associated with pulmonary tuberculosis (TB, TB lymphadenitits and latent TB, we examined mycobacterial antigen-specific immune responses of PTB, TBL and LTB individuals. More specifically, we examined ESAT-6 and CFP-10 induced Type 1, Type 2 and Type 17 cytokine production and their regulation using multiplex ELISA. RESULTS: PTB individuals exhibited a significantly lower baseline as well as antigen-specific production of Type 1 (IFNγ, TNFα and IL-2; Type 2 (IL-4 and Type 17 (IL-17A and IL-17F cytokines in comparison to both TBL and LTB individuals. TBL individuals exhibited significantly lower antigen-specific IFNγ responses alone in comparison to LTB individuals. Although, IL-10 levels were not significantly higher, neutralization of IL-10 during antigen stimulation resulted in significantly enhanced production of IFNγ, IL-4 and IL-17A in PTB individuals, indicating that IL-10 mediates (at least partially the suppression of cytokine responses in PTB. CONCLUSION: Pulmonary TB is characterized by an IL-10 dependent antigen-specific suppression of Type 1, Type 2 and Type 17 cytokines, reflecting an important association of these cytokines in the pathogenesis of active TB.

  8. Cytokinin activity induced by thidiazuron.

    Thomas, J C; Katterman, F R

    1986-06-01

    The diphenylurea derivative thidiazuron induces a variety of cytokinin responses. Levels above 5 x 10(-9) molar and 4 x 10(-7) molar stimulate maximum soybean callus growth and radish cotyledon expansion, respectively. A wider range of dose response related effects follows thidiazuron induced tobacco plant regeneration. Analysis of soybean callus extracts strongly suggests that thidiazuron treatment creates an accumulation and/or synthesis of purine cytokinins, able to induce the growth, expansion and regeneration, mentioned above. PMID:16664878

  9. Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen.

    NAGLER-ANDERSON, C; Bober, L A; Robinson, M E; Siskind, G W; Thorbecke, G. J.

    1986-01-01

    Although oral administration of protein antigens may lead to specific immunologic unresponsiveness, this method of immunoregulation has not been applied to models of autoimmune disease. Type II collagen-induced arthritis is an animal model of polyarthritis induced in susceptible mice and rats by immunization with type II collagen, a major component of cartilage. Intragastric administration of soluble type II collagen, prior to immunization with type II collagen in adjuvant, suppresses the inc...

  10. Tackling the Cytotoxic Effect of a Marine Polycyclic Quinone-Type Metabolite: Halenaquinone Induces Molt 4 Cells Apoptosis via Oxidative Stress Combined with the Inhibition of HDAC and Topoisomerase Activities

    Shou-Ping Shih

    2015-05-01

    Full Text Available A marine polycyclic quinone-type metabolite, halenaquinone (HQ, was found to inhibit the proliferation of Molt 4, K562, MDA-MB-231 and DLD-1 cancer cell lines, with IC50 of 0.48, 0.18, 8.0 and 6.76 μg/mL, respectively. It exhibited the most potent activity against leukemia Molt 4 cells. Accumulating evidence showed that HQ may act as a potent protein kinase inhibitor in cancer therapy. To fully understand the mechanism of HQ, we further explored the precise molecular targets in leukemia Molt 4 cells. We found that the use of HQ increased apoptosis by 26.23%–70.27% and caused disruption of mitochondrial membrane potential (MMP by 17.15%–53.25% in a dose-dependent manner, as demonstrated by Annexin-V/PI and JC-1 staining assays, respectively. Moreover, our findings indicated that the pretreatment of Molt 4 cells with N-acetyl-l-cysteine (NAC, a reactive oxygen species (ROS scavenger, diminished MMP disruption and apoptosis induced by HQ, suggesting that ROS overproduction plays a crucial rule in the cytotoxic activity of HQ. The results of a cell-free system assay indicated that HQ could act as an HDAC and topoisomerase catalytic inhibitor through the inhibition of pan-HDAC and topoisomerase IIα expression, respectively. On the protein level, the expression of the anti-apoptotic proteins p-Akt, NFκB, HDAC and Bcl-2, as well as hexokinase II was inhibited by the use of HQ. On the other hand, the expression of the pro-apoptotic protein Bax, PARP cleavage, caspase activation and cytochrome c release were increased after HQ treatment. Taken together, our results suggested that the antileukemic effect of HQ is ROS-mediated mitochondrial apoptosis combined with the inhibitory effect on HDAC and topoisomerase activities.

  11. Type Ia Supernovae and Accretion Induced Collapse

    Ruiter, A J; Sim, S A; Hillebrandt, W; Fink, M; Kromer, M

    2010-01-01

    Using the population synthesis binary evolution code StarTrack, we present theoretical rates and delay times of Type Ia supernovae arising from various formation channels. These channels include binaries in which the exploding white dwarf reaches the Chandrasekhar mass limit (DDS, SDS, and helium-rich donor scenario) as well as the sub-Chandrasekhar mass scenario, in which a white dwarf accretes from a helium-rich companion and explodes as a SN Ia before reaching the Chandrasekhar mass limit. We find that using a common envelope parameterization employing energy balance with alpha=1 and lambda=1, the supernova rates per unit mass (born in stars) of sub-Chandrasekhar mass SNe Ia exceed those of all other progenitor channels at epochs t=0.7 - 4 Gyr for a burst of star formation at t=0. Additionally, the delay time distribution of the sub-Chandrasekhar model can be divided in to two distinct evolutionary channels: the `prompt' helium-star channel with delay times 800 Myr spanning up to a Hubble time. These find...

  12. Stresslets induced by active swimmers

    Lauga, Eric

    2016-01-01

    Active particles disturb the fluid around them as force dipoles, or stresslets, which govern their collective dynamics. Unlike swimming speeds, the stresslets of active particles are rarely determined due to the lack of a suitable theoretical framework for arbitrary geometry. We propose a general method, based on the reciprocal theorem of Stokes flows, to compute stresslets as integrals of the velocities on the particle's surface, which we illustrate for spheroidal chemically-active particles. Our method will allow tuning the stresslet of artificial swimmers and tailoring their collective motion in complex environments.

  13. Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production.

    Hashimoto, Shin; Yamamoto, Soh; Ogasawara, Noriko; Sato, Toyotaka; Yamamoto, Keisuke; Katoh, Hiroshi; Kubota, Toru; Shiraishi, Tsukasa; Kojima, Takashi; Himi, Tetsuo; Tsutsumi, Hiroyuki; Yokota, Shin-Ichi

    2016-01-01

    Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection. PMID:27560627

  14. Heteromagnetic Microelectronics Microsystems of Active Type

    Ignatiev, Alexander A

    2010-01-01

    Heteromagnetic Microelectronics: Microsystems of Active Type, by Alexander A. Ignatiev of Saratov State University and Alexander V. Lyashenko of JSC Research Institute Tantal in Russia, offers a very detailed and specialized account of the author's research and development of heteromagnetic materials and devices. The book is based on original material from the author's programs of designing heteromagnetic microsystems. Polyvalent, multiple parameter magneto-semiconductor microsystems are described and the book reports on extensive experimental and theoretical results of research in a range of frequencies up to 1000 GHz. For the first time the direction of satisfying criteria, and burst technologies, which can make a subject of discovery, are discussed in great detail. This book is intended for post-graduate students and researchers specializing in the design and application of heteromagnetic materials and devices. Alexander A. Ignatiev is author of Magnetoelectronics of Microwaves and Extremely High Frequenci...

  15. Urokinase and type I plasminogen activator inhibitor production by normal human hepatocytes: modulation by inflammatory agents.

    Busso, N; Nicodeme, E; Chesne, C; Guillouzo, A; Belin, D; Hyafil, F

    1994-07-01

    We examined the effects of inflammatory cytokines (interleukin-1 beta, tumor necrosis factor-alpha and transforming growth factor-beta) on the plasminogen activator system (urokinase, tissue-type plasminogen activator, type 1 plasminogen activator inhibitor) in primary cultures of human hepatocytes. We show that interleukin-1 beta and tumor necrosis factor-alpha increase urokinase-type plasminogen activator production, reinforcing the concept that increased urokinase production is associated with inflammatory processes. By contrast, the same agents (i.e., interleukin-1 beta and tumor necrosis factor-alpha) do not stimulate plasminogen activator inhibitor type 1 production. This latter observation rules out hepatocytes as a major cellular source of plasmatic plasminogen activator inhibitor type 1 during acute-phase-related responses. Among the inflammatory agents used, transforming growth factor-beta was found to be the most effective modulator of both urokinase-type plasminogen activator and plasminogen activator inhibitor type 1, inducing severalfold increases of activity of urokinase-type plasminogen activator, antigen and the corresponding mRNA and increasing plasminogen activator inhibitor type 1 antigen and mRNA levels. Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 modulation by transforming growth factor-beta may play a critical role in hepatic pathophysiology. PMID:8020888

  16. Induced magnetic ordering transition in RCo5 type materials

    The magnetism in several materials of the RCo5 type is studied. A numerical calculation scheme, based on an induced magnetic ordering transition, is set up. Using this scheme, and previously reported crystalline electric and magnetic exchange fields parameters, the magnetic structure in R1−yYyCo3B2 and R(Co1−xNix)5 materials (R=Tb and Ho), and its temperature evolution, is calculated, and compared with the corresponding observed results. It is proposed that the magnetic order in the materials of the RCO5 type, with R3+ of integral J, is driven by an induced transition. - Highlights: • A numerical calculations scheme, that simulates induced transition magnetic ordering in R1−yYyCo3B2 and R(Co1−xNix)5 type materials, is set up. • The observed ordered magnetic moment of the R sub-lattice, as function of the magnetic exchange field, and as function of temperature, is shown to agree with induced transition theory, and not with Curie–Weiss theory. • In R1−yYyCo3B2, the relative magnitudes of the crystalline electric field and the magnetic exchange field are just above the critical threshold for induced transition ordering, making them the best experimental ‘realization’ found so far

  17. Exopolysaccharide from Trichoderma pseudokoningii induces macrophage activation.

    Wang, Guodong; Zhu, Lei; Yu, Bo; Chen, Ke; Liu, Bo; Liu, Jun; Qin, Guozheng; Liu, Chunyan; Liu, Huixia; Chen, Kaoshan

    2016-09-20

    In this study, we evaluated the immunomodulatory activity of an exopolysaccharide (EPS) derived from Trichoderma pseudokoningii and investigated the molecular mechanism of EPS-mediated activation of macrophages. Results revealed that EPS could significantly induce the production of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin (IL)-1β and enhance phagocytic activity in RAW 264.7 cells. Immunofluorescence staining indicated that EPS promoted the nuclear translocation of nuclear factor (NF)-κB p65 subunit. Western blot analysis showed that EPS increased the expression of inducible nitric oxide synthase (iNOS) protein, the degradation of IκB-α and the phosphorylation of mitogen-activated protein kinases (MAPKs). Furthermore, pretreatment of RAW 264.7 cells with specific inhibitors of NF-κB and MAPKs significantly attenuated EPS-induced TNF-α and IL-1β production. EPS also induced the inhibition of cytokine secretion by special antibodies against Toll-like receptor-4 (TLR4) and Dectin-1. These data suggest that EPS from Trichoderma pseudokoningii activates RAW 264.7 cells through NF-κB and MAPKs signaling pathways via TLR4 and Dectin-1. PMID:27261736

  18. Robust Type-specific Hemisynapses Induced by Artificial Dendrites

    Kim, Eun Joong; Jeon, Chang Su; Lee, Soo Youn; Hwang, Inseong; Chung, Taek Dong

    2016-04-01

    Type-specificity of synapses, excitatory and inhibitory, regulates information process in neural networks via chemical neurotransmitters. To lay a foundation of synapse-based neural interfaces, artificial dendrites are generated by covering abiotic substrata with ectodomains of type-specific synaptogenic proteins that are C-terminally tagged with biotinylated fluorescent proteins. The excitatory artificial synapses displaying engineered ectodomains of postsynaptic neuroligin-1 (NL1) induce the formation of excitatory presynapses with mixed culture of neurons in various developmental stages, while the inhibitory artificial dendrites displaying engineered NL2 and Slitrk3 induce inhibitory presynapses only with mature neurons. By contrast, if the artificial dendrites are applied to the axonal components of micropatterned neurons, correctly-matched synaptic specificity emerges regardless of the neuronal developmental stages. The hemisynapses retain their initially established type-specificity during neuronal development and maintain their synaptic strength provided live neurons, implying the possibility of durable synapse-based biointerfaces.

  19. Nrf2 activation prevents cadmium-induced acute liver injury

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H2DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice were

  20. Nrf2 activation prevents cadmium-induced acute liver injury

    Wu, Kai C. [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Liu, Jie J. [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)

    2012-08-15

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H{sub 2}DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice

  1. Two types of mental fatigue affect spontaneous oscillatory brain activities in different ways

    Shigihara Yoshihito; Tanaka Masaaki; Ishii Akira; Kanai Etsuko; Funakura Masami; Watanabe Yasuyoshi

    2013-01-01

    Abstract Background Fatigue has a multi-factorial nature. We examined the effects of two types of mental fatigue on spontaneous oscillatory brain activity using magnetoencephalography (MEG). Methods Participants were randomly assigned to two groups in a single-blinded, crossover fashion to perform two types of mental fatigue-inducing experiments. Each experiment consisted of a 30-min fatigue-inducing 0- or 2-back test session and two evaluation sessions performed just before and after the fat...

  2. Reflection-type electromagnetically induced transparency analogue in terahertz metamaterials

    A reflection-type electromagnetically induced transparency (EIT) metamaterial is proposed, which is composed of a dielectric spacer sandwiched with metallic patterns and metallic plane. Experimental results of THz time domain spectrum (THz-TDS) exhibit a typical reflection of EIT at 0.865 THz, which are in excellent agreement with the full-wave simulations. A multi-reflection theory is adopted to analyze the physical mechanism of the reflection-type EIT, showing that the reflection-type EIT is a superposition of multiple reflection of the transmission EIT. Such a reflection-type EIT provides many applications based on the EIT effect, such as slow light devices and nonlinear elements. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  3. Cisplatin-induced Casepase-3 activation in different tumor cells

    Shi, Hua; Li, Xiao; Su, Ting; Zhang, Yu-Hai

    2008-12-01

    Apoptosis plays an essential role in normal organism development which is one of the main types of programmed cell death to help tissues maintain homeostasis. Defective apoptosis can result in cell accumulation and therefore effects on tumor pathogenesis, progression and therapy resistance. A family of proteins, known as caspases, is typically activated in the early stages of apoptosis. Therefore, studying the kinetics of activation of caspases induced by antitumor drugs can contribute to antitumor drug discovery and explanation of the molecular mechanisms. This paper detected the Caspase-3 activity induced by cisplatin in human adenoid cystic carcinoma cell line (ACC-M), human hepatocellular liver carcinoma cell line (HepG2) and human epithelial carcinoma cell line (Hela) with stably expressing ECFP-DEVDDsRed (CD3) probe, a fluorescent probe consisting of Enhanced Cyan Fluorescent Protein (ECFP), red fluorescent protein (DsRed) and a linker with a recognition site of Caspase-3, by using the capillary electrophoresis (CE) and fluorescence resonance energy transfer (FRET) imaging system. Under the same concentration of cisplatin, ACC-M cells responded the most rapidly, and then HepG2 cells and Hela cells, respectively, in the early 30 hours. Later, HepG2 cells represented acceleration in the Caspase-3 activation speed and reached full activation the earliest comparing to other two cell types. The results demonstrated that ACC-M cell is more sensitive than the other two cell types under the treatment of cisplatin.

  4. Aqueous extract of Ficus religiosa linn. reduces oxidative stress in experimentally induced type 2 diabetic rats.

    Kirana, H; Agrawal, S S; Srinivasan, B P

    2009-10-01

    One of the major etiologies in pathogenesis of type 2 diabetes especially complications is oxidative stress. Aqueous extract of Ficus religiosa at a dose of 100 and 200 mg/kg orally decreased the fasting blood glucose in streptozotocin induced type 2 diabetic rats. The drug had enzyme induction effect with respect to catalase (CAT) and glutathione peroxidase (GSH-Px) activity, however decreased the exaggerated activity of superoxide dismutase (SOD) in type 2 diabetic rats. F. religiosa modulated the enzymes of antioxidant defence system to combat oxidative stress. As a result, glutathione (GSH-reduced form) was restored and inhibited the formation of malondialdehyde. Drug at higher dose (200 mg/kg) had more pronounced effect. F. religiosa, a rasayana group of plant drug having anti-diabetic activity along with antioxidant potential was beneficial in treatment of type 2 diabetes. PMID:20112810

  5. Electric current-induced lymphatic activation.

    Kajiya, Kentaro; Matsumoto-Okazaki, Yuko; Sawane, Mika; Fukada, Kaedeko; Takasugi, Yuya; Akai, Tomonori; Saito, Naoki; Mori, Yuichiro

    2014-12-01

    The lymphatic system in skin plays important roles in drainage of wastes and in the afferent phase of immune response. We previously showed that activation of vascular endothelial growth factor receptor (VEGFR), specifically the VEGFC/VEGFR-3 pathway, attenuates oedema and inflammation by promoting lymphangiogenesis, suggesting a protective role of lymphatic vessels against skin inflammation. However, it remains unknown how physical stimuli promote lymphatic function. Here, we show that lymphatic endothelial cells (LECs) are activated by direct-current (DC) electrical stimulation, which induced extension of actin filaments of LECs, increased calcium influx into LECs, and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK). An inhibitor of focal adhesion kinase, which plays a role in cellular adhesion and motility, diminished the DC-induced extension of F-actin and abrogated p38 phosphorylation. Time-lapse imaging revealed that pulsed-DC stimulation promoted proliferation and migration of LECs. Overall, these results indicate that electro-stimulation activates lymphatic function by activating p38 MAPK. PMID:25308203

  6. Barriers to Physical Activity Among Patients With Type 1 Diabetes

    Brazeau, Anne-Sophie; Rabasa-Lhoret, Rémi; Strychar, Irene; Mircescu, Hortensia

    2008-01-01

    OBJECTIVE—To determine, in an adult population with type 1 diabetes, barriers to regular physical activity using a diabetes-specific barriers measure (the Barriers to Physical Activity in Diabetes [type 1] [BAPAD1] scale) and factors associated with these barriers. RESEARCH DESIGN AND METHODS—One hundred adults with type 1 diabetes answered a questionnaire assessing perceived barriers to physical activity and related factors. A1C was obtained from the medical chart of each individual. RESULTS...

  7. Brain tumors induced in rats by human adenovirus type 12

    Murao,Tsuyoshi

    1974-02-01

    Full Text Available Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33 in SpragueDawley and 56% (14/25 in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.

  8. [Pseudocholinesterase activity in type 1 bipolar patients].

    Ezzaher, Asma; Haj Mouhamed, Dhouha; Mechri, Anwar; Neffati, Fadoua; Douki, Wahiba; Gaha, Lotfi; Najjar, Mohamed Fadhel

    2012-01-01

    This study aims to investigate the variation of pseudocholinesterase activity (BuChE) in bipolar patients and to explore its relation to the clinical and therapeutic characteristics of this disease. Our study included 105 patients with bipolar disorder and 100 control subjects aged 38.7 ± 12.2 and 36.4 ± 15.7 y, respectively. BuChE was determined by kinetic methods on Cobas Integra 400 plus™. Compared with controls, patients had a significantly higher pseudocholinesterase activity. Moreover, this increase was significantly associated (p = 0.001) with bipolar disorder with sensibility of 58% and specificity of 62% at threshold of 7392 IU/L. There was no significant change in pseudocholinesterase activity in relation to illness episodes and treatment, whereas the lowest values of this activity were seen in euthymic patients and those taking psychotics. Therefore, this activity is a real interest in the biological monitoring of patients as a risk factor for neurodegenerative diseases associated with bipolar disorder. But it would be most useful to evaluate their interest as a predictor of bipolar disorder in patients at risk. PMID:22294139

  9. HIFU-induced gene activation in vitro

    Liu, Yunbo; Zhong, Pei; Kon, Takashi; Li, Chuanyuan

    2001-05-01

    This work investigated the inducible gene activation in cancer cells that were sublethally injured during HIFU treatment. HeLa cells were transfected by an adenovirus vector that encodes GFP under the control of hsp70B promoter, leading to about 65% transfection efficiency. A volume of 10 μL transfected HeLa cells in suspension (5×107 cells/ml) were placed at the bottom of a PCR tube so that the cell suspension could be heated to a peak temperature of 50°C, 60°C, and 70°C for 120, 10, and 1 s, respectively, by a focused 1.1-MHz HIFU transducer operated at a peak negative pressure of -2.7 MPa at different duty cycles. One day after HIFU treatment, cell viability was determined to be 63%, 35%, and 18%, respectively, based on Trypan Blue exclusion test. Importantly, in all test groups, inducible GFP expression was detected in about 40%-50% of the surviving cells with GFP intensity increased by 25-fold based on flow cytometry analysis. These results demonstrate that even under the short exposure duration of HIFU treatment, inducible gene expression could be produced in sublethally injured cell population in vitro. Further studies are underway to explore the optimal HIFU condition for gene activation in vivo.

  10. Oleanolic Acid Induces the Type III Secretion System of Ralstonia solanacearum

    Wu, Dousheng; Ding, Wei; Zhang, Yong; Liu, Xuejiao; Yang, Liang

    2015-01-01

    Ralstonia solanacearum, the causal agent of bacterial wilt, can naturally infect a wide range of host plants. The type III secretion system (T3SS) is a major virulence determinant in this bacterium. Studies have shown that plant-derived compounds are able to inhibit or induce the T3SS in some plant pathogenic bacteria, though no specific T3SS inhibitor or inducer has yet been identified in R. solanacearum. In this study, a total of 50 different compounds were screened and almost half of them (22 of 50) significantly inhibited or induced the T3SS expression of R. solanacearum. Based on the strong induction activity on T3SS, the T3SS inducer oleanolic acid (OA) was chosen for further study. We found that OA induced the expression of T3SS through the HrpG-HrpB pathway. Some type III effector genes were induced in T3SS inducing medium supplemented with OA. In addition, OA targeted only the T3SS and did not affect other virulence determinants. Finally, we observed that induction of T3SS by OA accelerated disease progress on tobacco. Overall our results suggest that plant-derived compounds are an abundant source of R. solanacearum T3SS regulators, which could prove useful as tools to interrogate the regulation of this key virulence pathway. PMID:26732647

  11. Classifying sows' activity types from acceleration patterns

    Cornou, Cecile; Lundbye-Christensen, Søren

    three-dimensional axes, plus the length of the acceleration vector) are selected for each activity. Each time series is modeled using a Dynamic Linear Model with cyclic components. The classification method, based on a Multi-Process Kalman Filter (MPKF), is applied to a total of 15 times series of 120...

  12. UVB increases urokinase-type plasminogen activator receptor (uPAR) expression.

    Marschall, C; Lengyel, E; Nobutoh, T; Braungart, E; Douwes, K; Simon, A; Magdolen, V; Reuning, U; Degitz, K

    1999-07-01

    ultraviolet B induces urokinase-type plasminogen activator receptor. The epidermal induction of components of the proteolytic urokinase system by ultraviolet B may help explain the photoinducibility of pemphigus lesions. PMID:10417621

  13. Growing tumors induce a local STING dependent Type I IFN response in dendritic cells.

    Andzinski, Lisa; Spanier, Julia; Kasnitz, Nadine; Kröger, Andrea; Jin, Lei; Brinkmann, Melanie M; Kalinke, Ulrich; Weiss, Siegfried; Jablonska, Jadwiga; Lienenklaus, Stefan

    2016-09-15

    The importance of endogenous Type I IFNs in cancer immune surveillance is well established by now. Their role in polarization of tumor-associated neutrophilic granulocytes into anti-tumor effector cells has been recently demonstrated. Yet, the cellular source of Type I IFNs as well as the mode of induction is not clearly defined. Here, we demonstrate that IFN-β is induced by growing murine tumors. Induction is mainly mediated via STING-dependent signaling pathways, suggesting tumor derived DNA as trigger. Transcription factors IRF3 and IRF5 were activated under these conditions which is consistent with tumor infiltrating dendritic cells (DCs) being the major cellular source of IFN-β at the tumor site. Besides DCs, tumor cells themselves are induced to contribute to the production of IFN-β. Taken together, our data provide further information on immune surveillance by Type I IFNs and suggest novel potent cellular targets for future cancer therapy. PMID:27116225

  14. Different Types of Cell Death Induced by Enterotoxins

    Ming-Yuan Hong

    2010-08-01

    Full Text Available The infection of bacterial organisms generally causes cell death to facilitate microbial invasion and immune escape, both of which are involved in the pathogenesis of infectious diseases. In addition to the intercellular infectious processes, pathogen-produced/secreted enterotoxins (mostly exotoxins are the major weapons that kill host cells and cause diseases by inducing different types of cell death, particularly apoptosis and necrosis. Blocking these enterotoxins with synthetic drugs and vaccines is important for treating patients with infectious diseases. Studies of enterotoxin-induced apoptotic and necrotic mechanisms have helped us to create efficient strategies to use against these well-characterized cytopathic toxins. In this article, we review the induction of the different types of cell death from various bacterial enterotoxins, such as staphylococcal enterotoxin B, staphylococcal alpha-toxin, Panton-Valentine leukocidin, alpha-hemolysin of Escherichia coli, Shiga toxins, cytotoxic necrotizing factor 1, heat-labile enterotoxins, and the cholera toxin, Vibrio cholerae. In addition, necrosis caused by pore-forming toxins, apoptotic signaling through cross-talk pathways involving mitochondrial damage, endoplasmic reticulum stress, and lysosomal injury is discussed.

  15. Plasminogen activator inhibitor type 1 gene polymorphism and sepsis.

    Hermans, P.W.M.; Hazelzet, J.A.

    2005-01-01

    Plasminogen activator inhibitor type 1 (PAI-1) is a 50-kilodalton glycoprotein of the serine protease inhibitor family. The primary role of PAI-1 in vivo is the inhibition of both tissue- and urokinase-type plasminogen activators. In addition to this function, PAI-1 acts as an acute-phase protein du

  16. Type IV collagen-degrading enzyme activity in human serum.

    Hashimoto,Noriaki

    1988-02-01

    Full Text Available Type IV collagen-degrading enzyme activity was detected in human serum. Serum was preincubated with 4-aminophenylmercuric acetate and trypsin to activate the enzyme prior to assay. Type IV collagen, purified from human placentas and radiolabeled with [1-14C] acetic anhydride, was used as the substrate. The enzyme activity was measured at pH 7.5 and inhibited by treatment with ethylenediaminetetraacetic acid or heat. The assay of type IV collagen-degrading enzyme in human serum might be useful for estimating the degradation of type IV collagen.

  17. Activities induced in the human body by thermal neutrons

    Activities of 17 radionuclides induced in the human body by the activation of 14 elements with thermal neutrons were calculated. Resulting dependences of these activities on the activation time are shown in graphs. (author)

  18. Multiple mechanisms in serum factor-induced resistance of Haemophilus influenzae type b to antibody.

    Kuratana, M; Hansen, E J; Anderson, P

    1990-01-01

    Incubation of Haemophilus influenzae type b at less than or equal to 10(7) CFU/ml with serum ultrafiltrate induces a phenotypic conversion in which complement-mediated bactericidal activity by somatic antibodies decreases while killing by capsular antibody is unchanged. Conversion had been shown to occur in a capsule-deficient (b-) mutant of strain Eag (thus appearing independent of capsulation), to include an increase in lipopolysaccharide content, and to be inhibited by chloramphenicol or p...

  19. Dietary Hesperidin Exerts Hypoglycemic and Hypolipidemic Effects in Streptozotocin-Induced Marginal Type 1 Diabetic Rats

    Akiyama, Satoko; Katsumata, Shin-ichi; Suzuki, Kazuharu; Ishimi, Yoshiko; Wu, Jian; Uehara, Mariko

    2009-01-01

    Citrus bioflavonoids may offer some protection against the early stage of diabetes mellitus and the development of complications. We investigated the effect of hesperidin on blood glucose levels, hepatic glucose-regulating enzyme activities, serum insulin and adiponectin levels, serum and hepatic lipid levels, and parameters of bone loss in streptozotocin (STZ)-induced marginal type 1 diabetic rats. Weanling male rats were randomly assigned to experimental 3 groups: a control (C) group, a STZ...

  20. Effect of Eugenia Jambolana on Streptozotocin-Nicotinamide induced type-2 Diabetic Nephropathy in Rats

    Godwin Selvaraj Esther; Alvin Jose Manonmani

    2014-01-01

    The chronic type-2 diabetes mellitus leads to diabetic nephropathy, which is one of the major microvascular complication of end stage renal disease worldwide and causes premature death in diabetic patients. The objective of the present investigation was to evaluate the antidiabetic activity and protective effect of diabetic induced nephropathy of ethanolic extract of seeds of Eugenia jambolana (SEEJ) by using in-vitro and in-vivo models. The in-vitro antidiabetic effect was studied by glucose...

  1. 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle.

    Morgan, Stuart A

    2009-11-01

    Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity.

  2. Analysis of C-type lectin receptor induced NF-kappaB signaling

    Straßer, Andreas Dominikus

    2014-01-01

    Myeloid C-type lectin receptors (CLRs) that signal via Syk and the central Card9-Bcl10-Malt1 (CBM) complex induce the transcription of NF-κB-regulated genes. Activation of those receptors mediates inflammatory reactions and the defense against various pathogens. Despite the non-redundant role of CLRs for the induction of innate immune responses, particularly receptor-proximal events that transduce ligand binding to downstream signaling remain to be defined. This dissertation identifies PKCδ a...

  3. Involvement of inward rectifier and M-type currents in carbachol-induced epileptiform synchronization.

    Cataldi, Mauro; Panuccio, Gabriella; Cavaccini, Anna; D'Antuono, Margherita; Taglialatela, Maurizio; Avoli, Massimo

    2011-03-01

    Exposure to cholinergic agonists is a widely used paradigm to induce epileptogenesis in vivo and synchronous activity in brain slices maintained in vitro. However, the mechanisms underlying these effects remain unclear. Here, we used field potential recordings from the lateral entorhinal cortex in horizontal rat brain slices to explore whether two different K(+) currents regulated by muscarinic receptor activation, the inward rectifier (K(IR)) and the M-type (K(M)) currents, have a role in carbachol (CCh)-induced field activity, a prototypical model of cholinergic-dependent epileptiform synchronization. To establish whether K(IR) or K(M) blockade could replicate CCh effects, we exposed slices to blockers of these currents in the absence of CCh. K(IR) channel blockade with micromolar Ba(2+) concentrations induced interictal-like events with duration and frequency that were lower than those observed with CCh; by contrast, the K(M) blocker linopirdine was ineffective. Pre-treatment with Ba(2+) or linopirdine increased the duration of epileptiform discharges induced by subsequent application of CCh. Baclofen, a GABA(B) receptor agonist that activates K(IR), abolished CCh-induced field oscillations, an effect that was abrogated by the GABA(B) receptor antagonist CGP 55845, and prevented by Ba(2+). Finally, when applied after CCh, the K(M) activators flupirtine and retigabine shifted leftward the cumulative distribution of CCh-induced event duration; this effect was opposite to what seen during linopirdine application under similar experimental conditions. Overall, our findings suggest that K(IR) rather than K(M) plays a major regulatory role in controlling CCh-induced epileptiform synchronization. PMID:21144855

  4. Smad, but not MAPK, pathway mediates the expression of type I collagen in radiation induced fibrosis

    Highlights: ► We examine how radiation affects the expression level and signal pathway of collagen. ► TGF-β1 mRNA is elevated earlier than those of collagen genes after irradiation. ► Smad pathway mediates the expression of collagen in radiation induced fibrosis. ► MAPK pathways are not affected in the expression of collagen after irradiation. -- Abstract: Radiation induced fibrosis occurs following a therapeutic or accidental radiation exposure in normal tissues. Tissue fibrosis is the excessive accumulation of collagen and other extracellular matrix components. This study investigated how ionizing radiation affects the expression level and signal pathway of type I collagen. Real time RT-RCR showed that both α1and α2 chain of type I collagen mRNA were elevated from 48 h after irradiation with 10 Gy in NIH3T3 cells. The relative luciferase activities of both genes and type I collagen marker were elevated at 72 h. TGF-β1 mRNA was elevated earlier than those of type I collagen genes. A Western blot analysis showed the elevation of Smad phosphorylation at 72 h. Conversely, treatment with TGF-β receptor inhibitor inhibited the mRNA and relative luciferase activity of type I collagen. The phosphorylation of Smad was repressed with the inhibitor, and the luciferase activity was cancelled using a mutant construct of Smad binding site of α2(I) collagen gene. However, the MAPK pathways, p38, ERK1/2 and JNK, were not affected with specific inhibitors or siRNA. The data showed that the Smad pathway mediated the expression of type I collagen in radiation induced fibrosis.

  5. Type IV collagen-degrading enzyme activity in hepatocellular carcinoma.

    Nakatsukasa,Harushige

    1986-01-01

    Type IV collagen-degrading enzyme activity was measured in liver homogenate obtained from 10 patients with hepatocellular carcinomas. Type IV collagen, the enzyme substrate, was extracted from human placenta with pepsin digestion, and labeled with [1-14C] acetic anhydride. The homogenate was preincubated with p-aminophenylmercuric acetate to activate the latent form of the enzyme, and then the enzyme activity was measured at pH 7.5 by adding a substrate mixture. Referring to previous reports,...

  6. Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase.

    Austin, Michael B; Saito, Tamao; Bowman, Marianne E; Haydock, Stephen; Kato, Atsushi; Moore, Bradley S; Kay, Robert R; Noel, Joseph P

    2006-09-01

    Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two approximately 3,000-residue D. discoideum proteins, termed 'steely', as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) but feature an iterative type III polyketide synthase (PKS) in place of the expected FAS C-terminal thioesterase used to off load fatty acid products. This new domain arrangement likely facilitates covalent transfer of steely N-terminal acyl products directly to the C-terminal type III PKS active sites, which catalyze both iterative polyketide extension and cyclization. The crystal structure of a steely C-terminal domain confirms conservation of the homodimeric type III PKS fold. These findings suggest new bioengineering strategies for expanding the scope of fatty acid and polyketide biosynthesis. PMID:16906151

  7. Daily physical activity and type 2 diabetes: A review

    Hamasaki, Hidetaka

    2016-01-01

    Physical activity improves glycemic control and reduces the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes (T2D). Moderate to vigorous physical activity is recommended to manage T2D; however, patients with T2D can be physically weak, making it difficult to engage in the recommended levels of physical activity. Daily physical activity includes various activities performed during both occupational and leisure time such as walking, gardening, and housework th...

  8. Prevention of ultraviolet radiation‑induced immunosuppression by sunscreen in Candida albicans‑induced delayed‑type hypersensitivity.

    Chen, Quan; Li, Runxiang; Zhao, Xiaoxia; Liang, Bihua; Ma, Shaoyin; Li, Zhenjie; Zhu, Huilan

    2016-07-01

    Ultraviolet (UV) radiation-induced immunosuppression leading to skin cancer has received increased attention in previous years. The present study aimed to investigate the immunoprotection offered by Anthelios sunscreen in a mouse model of Candida albicans‑induced delayed‑type hypersensitivity. Anthelios sunscreen was applied to the skin on the dorsal skin of BALB/c mice treated with a sub‑erythema dose of solar‑simulated radiation. Delayed‑type hypersensitivity was induced by immunization with Candida albicans. Changes in the skin thickness of the foot pads were measured, and immunosuppression rates were also evaluated. The expression levels of CD207, CD80 and CD86 in the Langerhans cells were semi‑quantitatively detected using Western blotting and immunohistochemical assays. The delayed‑type hypersensitivity mouse model was successfully established. The minimal erythema doses of UVA and UVB exposure to the mice were 2,000 and 145 mJ/cm2, respectively. The immunosuppression rates in the sunscreen group and non‑sunscreen group were 24.39 and 65.85%, respectively (P<0.01). The results of the Western blotting and immunohistochemistry showed that the expression levels of CD207 (P<0.01), CD80 (P<0.05) and CD86 (P<0.01) were higher in the sunscreen group, compared with those in the non‑sunscreen group. UV exposure reduced Candida albicans antigen‑induced delayed‑type hypersensitivity. Anthelios sunscreen was found to protect the skin from immunosuppression through the activation of epidermal Langerhans cells. PMID:27175551

  9. Immune polarization by hookworms: taking cues from T helper type 2, type 2 innate lymphoid cells and alternatively activated macrophages.

    Nair, Meera G; Herbert, De'Broski R

    2016-06-01

    Cellular and molecular investigation of parasitic helminth infections has greatly accelerated the understanding of type 2 immune responses. However, there remains considerable debate regarding the specific leucocytes that kill parasites and whether these mechanisms are distinct from those responsible for tissue repair. Herein, we chronicle discoveries over the past decade highlighting current paradigms in type 2 immunity with a particular emphasis upon how CD4(+) T helper type 2 cells, type 2 innate lymphoid cells and alternatively activated macrophages coordinately control helminth-induced parasitism. Primarily, this review will draw from studies of the murine nematode parasite Nippostrongylus brasiliensis, which bears important similarities to the human hookworms Ancylostoma duodenale and Necator americanus. Given that one or more hookworm species currently infect millions of individuals across the globe, we propose that vaccine and/or pharmaceutical-based cure strategies targeting these affected human populations should incorporate the conceptual advances outlined herein. PMID:26928141

  10. Activation induced deaminase: how much and where?

    Orthwein, Alexandre; Di Noia, Javier M

    2012-08-01

    Activation induced deaminase (AID) plays a central role in adaptive immunity by initiating the processes of somatic hypermutation (SHM) and class switch recombination (CSR). On the other hand, AID also predisposes to lymphoma and plays a role in some autoimmune diseases, for which reasons AID expression and activity are regulated at various levels. Post-translational mechanisms regulating the amount and subcellular localization of AID are prominent in balancing AID physiological and pathological functions in B cells. Mechanisms regulating AID protein levels include stabilizing chaperones in the cytoplasm and proteins efficiently targeting AID to the proteasome within the nucleus. Nuclear export and cytoplasmic retention contribute to limit the amount of AID accessing the genome. Additionally, a number of factors have been implicated in AID active nuclear import. We review these intertwined mechanisms proposing two scenarios in which they could interact as a network or as a cycle for defining the optimal amount of AID protein. We also comparatively review the expression levels of AID necessary for its function during the immune response, present in different cancers as well as in those tissues in which AID has been implicated in epigenetic remodeling of the genome by demethylating DNA. PMID:22687198

  11. Type IV collagen-degrading enzyme activity in human serum.

    Hashimoto, Noriaki; Kobayashi,Michio; Watanabe,Akiharu; Higashi,Toshiro; Tsuji, Takao

    1988-01-01

    Type IV collagen-degrading enzyme activity was detected in human serum. Serum was preincubated with 4-aminophenylmercuric acetate and trypsin to activate the enzyme prior to assay. Type IV collagen, purified from human placentas and radiolabeled with [1-14C] acetic anhydride, was used as the substrate. The enzyme activity was measured at pH 7.5 and inhibited by treatment with ethylenediaminetetraacetic acid or heat. The assay of type IV collagen-degrading enzyme in human serum might be useful...

  12. C-type RNA viruses as possible predictors of radiation-induced bone oncogenesis

    Radium-224-induced osteosarcomas of (C3H X 101)F1 mice have been investigated for the presence of C-type RNA viruses. C-type virus particles with the typical properties of RNA tumour viruses could be detected by electron microscopic, biochemical and in-vitro studies. In a long-term experiment, the expression of C-type RNA virus particles was studied during the latency period and correlated with the appearance of osteosarcomas. The tumour incidence in this experiment was 100% with 40-50% of the tumours appearing in the 11th to 12th month after the start of the radiation. C-type RNA virus expression could be found in the 1st month and in the 11th and 12th months. These results indicate a transient virus activation shortly after starting the radiation, and a second peak of virus expression coinciding with the appearance of the osteosarcomas. (author)

  13. Physical Activity in Youth With Type 1 Diabetes: a Review.

    Tully, Carrie; Aronow, Laura; Mackey, Eleanor; Streisand, Randi

    2016-09-01

    Youth with type 1 diabetes are at risk for developing cardiovascular disease, and regular physical activity is strongly recommended as one strategy for prevention, as well as for good glycemic control. Despite recommendations, families in this pediatric population face unique barriers to physical activity, including fear of hypoglycemia. Moreover, families are not routinely counseled in the specific health and psychosocial benefits of following physical activity recommendations for youth with type 1 diabetes. To bridge this gap, the recent literature regarding physical activity in children with type 1 diabetes is reviewed with particular focus on young children. A discussion of the limitations of the current body of research, and recommendations for objectively measured physical activity are provided. Specific recommendations for clinical practice are given, including provider endorsements for regular physical activity for longer than 60 minutes, at least three times a week. PMID:27475093

  14. Activation of mitogen activated protein kinases via complement receptor type 2

    LUO Min-hua 罗敏华; CHEN Ming-liang 陈明亮; Heribert Stoiber; Manfred P Dierich

    2004-01-01

    Background Complement receptor type 2 (CR2) is the receptor for C3d and C3dg and for Epstein-Barr virus. The aim of our study was to explore whether CR2 can independently mediate the activation of mitogen-activated protein kinases (MAPKs, including ERK, JNK, and p38MAPK), and to highlight the molecular mechanism of CD4+ cell deletion in AIDS.Results FACS results showed that the positive rates of HOS-CR2 and HOS-CD4CR2 cells were greater than 96%, and Western blot showed that the CR2 expression levels on HOS-CR2 and HOS-CD4CR2 cells were high. Activation and blocking tests of MAPKs (ERK, JNK, and p38MAPK) were carried out in HOS-CR2, HOS-CD4, and HOS-CD4CR2 cells. The activation of MAPKs in HOS-CR2 cells stimulated with PMA (100 ng/ml) and NHS (10%) was identical. The activation of MAPKs increased at 5 minutes, reached a peak at 10 minutes, and decreased to baseline within 30 minutes, all in a time-dependent manner; the activation of MAPKs was blocked by anti-CR2 McAb, PD98059 (inhibitor of ERK), and Wortmanin (inhibitor of PI-3K), respectively. In HOS-CD4 cells, MAPKs were activated by HIV-gp160. In HOS-CD4CR2 cells, MAPK activation was induced by HIV-gp160, 10% NHS, and HIV-gp160+10%NHS; phosphorylation of p38MAPK was dramatically induced by HIV-gp160+NHS, and lasted for 1 hour. The cell proliferation results showed that HIV-gp160 inhibited the proliferation of HOS-CD4 and HOS-CD4CR2 cells (P<0.01) and that NHS enhanced the effect of HIV-gp160 (P<0.01).Conclusions The activation of MAPKs is independently mediated by CR2 and that anti-CR2 McAb, PD98059, and Wortmanin block the activation of MAPKs, respectively. The results of the signal transduction and cell proliferation assays of HOS-CD4CR2 cells show that CR2 plays a role in the pathogenesis of HIV infection, especially in the inhibition of CD4+ cell proliferation.

  15. Changing Physical Activity Behavior in Type 2 Diabetes

    Avery, L.; Flynn, D.; Wersch, A.; Sniehotta, F. F.; Trenell, M. I.

    2012-01-01

    OBJECTIVE Behavioral interventions targeting “free-living” physical activity (PA) and exercise that produce long-term glycemic control in adults with type 2 diabetes are warranted. However, little is known about how clinical teams should support adults with type 2 diabetes to achieve and sustain a physically active lifestyle. RESEARCH DESIGN AND METHODS We conducted a systematic review of randomized controlled trials (RCTs) (published up to January 2012) to establish the effect of behavioral ...

  16. Physical Activity and Type 1 Diabetes: Time for a Rewire?

    Colberg, Sheri R; Laan, Remmert; Dassau, Eyal; Kerr, David

    2015-01-01

    While being physically active bestows many health benefits on individuals with type 1 diabetes, their overall blood glucose control is not enhanced without an effective balance of insulin dosing and food intake to maintain euglycemia before, during, and after exercise of all types. At present, a number of technological advances are already available to insulin users who desire to be physically active with optimal blood glucose control, although a number of limitations to those devices remain....

  17. The locations and types of complementary activities on Slovene highways

    Boris Jagodič

    1994-01-01

    Full Text Available The article is a summary of a few chapters of the research The locations and types of complementary activities on Slovene highways. The number of complementary locations, regulations concerning construction and types of complementary locations are thoroughly discussed. Emphasis is given to the modification of criteria, which apply to the positioning of complementary activities on highways, amongst other because of characteristics of the terrain and the polycentric pattern of settlements.

  18. Amikacin-induced type 5 Bartter-like syndrome with severe hypocalcemia

    Chrispal A

    2009-01-01

    Full Text Available Aminoglycoside-induced renal toxicity is well known and may manifest with nonoliguric renal failure or renal tubular dysfunction. Aminoglycoside-induced renal tubular dysfunction could result in diffuse damage or manifest as a Fanconi-like syndrome, Bartter-like syndrome, or distal renal tubular acidosis. We discuss a patient who developed severe renal tubular dysfunction secondary to short-term therapy with Amikacin, resulting in refractory hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis, and polyuria. This constellation of biochemical abnormalities mimic Type 5 Bartter′s syndrome, where there is activating mutation of the calcium sensing receptor in the thick ascending loop of Henle and the distal tubule. In this case this activation of the calcium sensing receptor was triggered by amikacin. This phenomenon has been described with gentamicin though never with amikacin. Recovery of the tubular dysfunction took 15 days following cessation of the offending drug, Amikacin.

  19. Proteins of 30 and 36 kilodaltons, membrane constituents of the Staphylococcus aureus L form, induce production of tumor necrosis factor alpha and activate the human immunodeficiency virus type 1 long terminal repeat.

    Akashi, A; Ono, S.; Kuwano, K.; Arai, S

    1996-01-01

    We have previously demonstrated that the membrane of the Staphylococcus aureus L form induced tumor necrosis factor alpha (TNF-alpha) from murine macrophages. In this study, we purified two proteins which induce TNF-alpha production from a human monocytic cell line, THP-1, and murine macrophages. These molecules were purified from delipidated membranes by deoxycholic acid extraction, two-step anion-exchange chromatography, and preparative electrophoresis. Sodium dodecyl sulfate-polyacrylamide...

  20. Aggregation activity of blood formed elements in patients with type 1 and type 2 diabetes mellitus

    Boris Il'ich Kuznik; Yuriy Antonovich Vitkovskiy; Marina Yur'evna Zakharova; Natal'ya Nikolaevna Klyuchereva; Ol'ga Sergeevna Rodnina; Aleksey Vladimirovich Solpov

    2012-01-01

    Aims. To assess differences in blood formed elements aggregation activity in patients with type 1 (T1) and type 2 (T2) diabetes mellitus (DM). Materials and methods. We studied blood samples from 88 patients with T1 and T2 DM. Platelet aggregation activity was assessed by means of «Biola» aggregometer; we also determined platelet-lymphocyte and leucocyte-erythrocyte adhesion intensity. Results. We show that spontaneous platelet aggregation is markedly increased in patients with T1...

  1. Denbinobin induces apoptosis in human lung adenocarcinoma cells via Akt inactivation, Bad activation, and mitochondrial dysfunction.

    Kuo, Chen-Tzu; Hsu, Ming-Jen; Chen, Bing-Chang; Chen, Chien-Chih; Teng, Che-Ming; Pan, Shiow-Lin; Lin, Chien-Huang

    2008-02-28

    Increasing evidence demonstrated that denbinobin, isolated from Ephemerantha lonchophylla, exert cytotoxic effects in cancer cells. The purpose of this study was to investigate whether denbinobin induces apoptosis and the apoptotic mechanism of denbinobin in human lung adenocarcinoma cells (A549). Denbinobin (1-20microM) caused cell death in a concentration-dependent manner. Flow cytometric analysis and annexin V labeling demonstrated that denbinobin increased the percentage of apoptotic cells. A549 cells treated with denbinobin showed typical characteristics of apoptosis including morphological changes and DNA fragmentation. Denbinobin induced caspase 3 activation, and N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a broad-spectrum caspase inhibitor, prevented denbinobin-induced cell death. Denbinobin induced the loss of the mitochondrial membrane potential and the release of mitochondrial apoptotic proteins including cytochrome c, second mitochondria derived activator of caspase (Smac), and apoptosis-inducing factor (AIF). In addition, denbinobin-induced Bad activation was accompanied by the dissociation of Bad with 14-3-3 and the association of Bad with Bcl-xL. Furthermore, denbinobin induced Akt inactivation in a time-dependent manner. Transfection of A549 cells with both wild-type and constitutively active Akt significantly suppressed denbinobin-induced Bad activation and cell apoptosis. These results suggest that Akt inactivation, followed by Bad activation, mitochondrial dysfunction, caspase 3 activation, and AIF release, contributes to denbinobin-induced cell apoptosis. PMID:18262737

  2. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells

    Ionizing radiation (IR) therapy is a primary treatment for glioblastoma multiforme (GBM), a common and devastating brain tumor in humans. IR has been shown to induce PI3K-Akt activation in many cell types, and activation of the PI3K-Akt signaling pathway has been correlated with radioresistance. Initially, the effects of IR on Akt activation were assessed in multiple human GBM cell lines. Next, to evaluate a potential causative role of IR-induced Akt activation on radiosensitivity, Akt activation was inhibited during IR with several complementary genetic and pharmacological approaches, and radiosensitivity measured using clonogenic survival assays. Three of the eight cell lines tested demonstrated IR-induced Akt activation. Further studies revealed that IR-induced Akt activation was dependent upon the presence of a serum factor, and could be inhibited by the EGFR inhibitor AG1478. Inhibition of PI3K activation with LY294002, or with inducible wild-type PTEN, inhibition of EGFR, as well as direct inhibition of Akt with two Akt inhibitors during irradiation increased the radiosensitivity of U87MG cells. These results suggest that Akt may be a central player in a feedback loop whereby activation of Akt induced by IR increases radioresistance of GBM cells. Targeting the Akt signaling pathway may have important therapeutic implications when used in combination with IR in the treatment of a subset of brain tumor patients

  3. Plant type improvement of indigenous rice cultivars through induced mutations

    A high yielding, locally adapted cultivar 'Afaa Mwanza 1/159' of rice (Oryza sativa L.) which is tall and late in maturity, was irradiated with gamma rays at doses of 170, 210 and 250 Gy to shorten plant height and time of maturity. Twelve mutants were selected, and evaluated for yield performance in field trials from M6 to M9 generations. All the mutants were shorter in plant height, and gave higher mean yield than the parent. Correlation coefficient analysis showed that the number of productive tillers, number of panicles per square meter and grain filling in the panicle were important characters which influenced yield. On the other hand, panicle length had negative influence on yield. Cv. 'Supa India' and 'Salama' were also irradiated with doses of 170, 210, 240 Gy gamma rays. Analysis of M2 populations of these cultivars indicated that mutagenesis created a lot of variation in plant height, maturity, spikelet fertility and panicle length. The induced variation shall be useful in selecting desired plant types. (author). 16 refs, 12 tabs

  4. Reelin induces EphB activation

    Elisabeth Bouché; Mario I Romero-Ortega; Mark Henkemeyer; Timothy Catchpole; Jost Leemhuis; Michael Frotscher; Petra May

    2013-01-01

    The integration of newborn neurons into functional neuronal networks requires migration of cells to their final position in the developing brain,the growth and arborization of neuronal processes and the formation of synaptic contacts with other neurons.A central player among the signals that coordinate this complex sequence of differentiation events is the secreted glycoprotein Reelin,which also modulates synaptic plasticity,learning and memory formation in the adult brain.Binding of Reelin to ApoER2 and VLDL receptor,two members of the LDL receptor family,initiates a signaling cascade involving tyrosine phosphorylation of the intracellular cytoplasmic adaptor protein Disabled-l,which targets the neuronal cytoskeleton and ultimately controls the positioning of neurons throughout the developing brain.However,it is possible that Reelin signals interact with other receptor-mediated signaling cascades to regulate different aspects of brain development and plasticity.EphB tyrosine kinases regulate cell adhesion and repulsion-dependent processes via bidirectional signaling through ephrin B transmembrane proteins.Here,we demonstrate that Reelin binds to the extracellular domains of EphB transmembrane proteins,inducing receptor clustering and activation of EphB forward signaling in neurons,independently of the ‘classical' Reelin receptors,ApoER2 and VLDLR.Accordingly,mice lacking EphB1 and EphB2 display a positioning defect of CA3 hippocampal pyramidal neurons,similar to that in Reelin-deficient mice,and this cell migration defect depends on the kinase activity of EphB proteins.Together,our data provide biochemical and functional evidence for signal integration between Reelin and EphB forward signaling.

  5. Bromocriptine induces parapoptosis as the main type of cell death responsible for experimental pituitary tumor shrinkage

    Bromocriptine (Bc) produces pituitary tumoral mass regression which induces the cellular death that was classically described as apoptosis. However, recent works have related that other mechanisms of cell death could also be involved in the maintenance of physiological and pathological pituitary homeostasis. The aim of this study was to evaluate and characterize the different types of cell death in the involution induced by Bc in experimental rat pituitary tumors. The current study demonstrated that Bc induced an effective regression of estrogen induced pituitary tumors by a mechanism identified as parapoptosis. This alternative cell death was ultrastructurally recognized by extensive cytoplasmic vacuolization and an increased cell electron density, represented around 25% of the total pituitary cells counted. Furthermore, the results obtained from biochemical assays did not correspond to the criteria of apoptosis or necrosis. We also investigated the participation of p38, ERK1/2 and PKCδ in the parapoptotic pathway. An important observation was the significant increase in phosphorylated forms of these MAPKs, the holoenzyme and catalytic fragments of PKCδ in nuclear fractions after Bc administration compared to control and estrogen treated rats. Furthermore, the immunolocalization at ultrastructural level of these kinases showed a similar distribution pattern, with a prevalent localization at nuclear level in lactotrophs from Bc treated rats. In summary, we determined that parapoptosis is the predominant cell death type involved in the regression of pituitary tumors in response to Bc treatment, and may cause the activation of PKCδ, ERK1/2 and p38.

  6. Toxoplasma gondii Chitinase Induces Macrophage Activation.

    Fausto Almeida

    Full Text Available Toxoplasma gondii is an obligate intracellular protozoan parasite found worldwide that is able to chronically infect almost all vertebrate species, especially birds and mammalians. Chitinases are essential to various biological processes, and some pathogens rely on chitinases for successful parasitization. Here, we purified and characterized a chitinase from T. gondii. The enzyme, provisionally named Tg_chitinase, has a molecular mass of 13.7 kDa and exhibits a Km of 0.34 mM and a Vmax of 2.64. The optimal environmental conditions for enzymatic function were at pH 4.0 and 50 °C. Tg_chitinase was immunolocalized in the cytoplasm of highly virulent T. gondii RH strain tachyzoites, mainly at the apical extremity. Tg_chitinase induced macrophage activation as manifested by the production of high levels of pro-inflammatory cytokines, a pathogenic hallmark of T. gondii infection. In conclusion, to our knowledge, we describe for the first time a chitinase of T. gondii tachyzoites and provide evidence that this enzyme might influence the pathogenesis of T. gondii infection.

  7. Activation of Protease-Activated Receptor 2 Induces VEGF Independently of HIF-1

    Rasmussen, Jeppe Grøndahl; Riis, Simone Elkjær; Frøbert, Ole; Yang, Sufang; Kastrup, Jens; Zachar, Vladimir; Simonsen, Ulf; Fink, Trine

    2012-01-01

    Background Human adipose stem cells (hASCs) can promote angiogenesis through secretion of proangiogenic factors such as vascular endothelial growth factor (VEGF). In other cell types, it has been shown that induction of VEGF is mediated by both protease activated receptor 2 (PAR2) and hypoxia inducible factor 1(HIF-1). The present study hypothesized that PAR2 stimulation through activation of kinase signaling cascades lead to induction of HIF-1 and secretion of VEGF. Methodology/Principal Findings Immunohistochemistry revealed the expression of PAR2 receptors on the surface of hASCs. Blocking the PAR2 receptors with a specific antibody prior to trypsin treatment showed these receptors are involved in trypsin-evoked increase in VEGF secretion from hASCs. Blocking with specific kinase inhibitors suggested that that activation of MEK/ERK and PI3-kinase/Akt pathways are involved in trypsin-eveoked induction of VEGF. The effect of the trypsin treatment on the transcription of VEGF peaked at 6 hours after the treatment and was comparable to the activation observed after keeping hASCs for 24 hours at 1% oxygen. In contrast to hypoxia, trypsin alone failed to induce HIF-1 measured with ELISA, while the combination of trypsin and hypoxia had an additive effect on both VEGF transcription and secretion, results which were confirmed by Western blot. Conclusion In hASCs trypsin and hypoxia induce VEGF expression through separate pathways. PMID:23049945

  8. Mobile application to induce lifestyle modifications in type 2 diabetic patients: prototype based on international guidelines

    García-Jaramillo, M.; Delgado, J. S.; León-Vargas, F.

    2015-12-01

    This paper describes a prototype app to induce lifestyle modifications in newly diagnosed type 2 diabetic patients. The app design is based on International Diabetes Federation guidelines and recommendations from clinical studies related to diabetes health-care. Two main approaches, lifestyle modification and self-management education are used owing to significant benefits reported. The method used is based on setting goals under medical support related to physical activity, nutritional habits and weight loss, in addition to educational messages. This is specially implemented to address the main challenges that have limited the success of similar mobile applications already validated on diabetic patients. A traffic light is used to show the overall state of the goals compliance. This state could be understood as excellent (green), there are aspects to improve (yellow), or some individual goals are not carrying out (red). An example of how works this method is presented in results. Furthermore, the app provides recommendations to the user in case the overall state was in yellow or red. The recommendations pretend to induce the user to make changes in their eating habits and physical activity. According to international guidelines and clinical studies, a prototype of mobile application to induce a lifestyle modification in order to prevent adverse risk factors related to diabetes was presented. The resulting application is apparently consistent with clinical judgments, but a formal clinical validation is required. The effectiveness of this app is currently under consideration for the Colombian population with type 2 diabetes.

  9. Gene activation by induced DNA rearrangements

    A murine cell line (EN/NIH) containing the retroviral vector ZIPNeoSV(x)1 that was modified by deletion of the enhancer elements in the viral long terminal repeats has been used as an assay system to detect induced DNA rearrangements that result in activation of a transcriptionally silent reporter gene encoded by the viral genome. The spontaneous frequency of G418 resistance is less than 10(-7), whereas exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or the combination of UV irradiation plus TPA resulted in the emergence of drug resistant cell lines at a frequency of 5 per 10(6) and 67 per 10(6) cells, respectively. In several of the cell lines that were analyzed a low level of amplification of one of the two parental retroviral integrants was observed, whereas in others no alteration in the region of the viral genome was detected. To determine the effect of the SV40 large T antigen on induced DNA rearrangements, EN/NIH cells were transfected with a temperature sensitive (ts) mutant of SV40 T. Transfectants were maintained at the permissive temperature (33 degrees C) for varying periods of time (1-5 days) in order to vary SV40 T antigen exposure, after which they were shifted to 39.5 degrees C for selection in G418. The frequency of emergence of drug resistant cell clones increased with duration of exposure to large T antigen (9-52 per 10(6) cells over 1-5 days, respectively), and all cell lines analyzed demonstrated DNA rearrangements in the region of the neo gene. A novel 18-kilobase pair XbaI fragment was cloned from one cell line which revealed the presence of a 2.0-kilobase pair EcoRI segment containing an inverted duplication which hybridized to neo sequences. It is likely that the observed rearrangement was initiated by the specific binding of large T antigen to the SV40 origin of replication encoded within the viral genome

  10. Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require Functional Angiotensin Type 1a Receptors.

    Briet, Marie; Barhoumi, Tlili; Mian, Muhammad Oneeb Rehman; Coelho, Suellen C; Ouerd, Sofiane; Rautureau, Yohann; Coffman, Thomas M; Paradis, Pierre; Schiffrin, Ernesto L

    2016-05-01

    We investigated the role of angiotensin type 1a receptors (AGTR1a) in vascular injury induced by aldosterone activation of mineralocorticoid receptors inAgtr1a(-/-)and wild-type (WT) mice infused with aldosterone for 14 days while receiving 1% NaCl in drinking water. Aldosterone increased systolic blood pressure (BP) by ≈30 mm Hg in WT mice and ≈50 mm Hg inAgtr1a(-/-)mice. Aldosterone induced aortic and small artery remodeling, impaired endothelium-dependent relaxation in WT mice, and enhanced fibronectin and collagen deposition and vascular inflammation. None of these vascular effects were observed inAgtr1a(-/-)mice. Aldosterone effects were prevented by the AGTR1 antagonist losartan in WT mice. In contrast to aldosterone, norepinephrine caused similar BP increase and mesenteric artery remodeling in WT andAgtr1a(-/-)mice.Agtr1a(-/-)mice infused with aldosterone did not increase sodium excretion in response to a sodium chloride challenge, suggesting that sodium retention could contribute to the exaggerated BP rise induced by aldosterone.Agtr1a(-/-)mice had decreased mesenteric artery expression of the calcium-activated potassium channelKcnmb1, which may enhance myogenic tone and together with sodium retention, exacerbate BP responses to aldosterone/salt inAgtr1a(-/-)mice. We conclude that although aldosterone activation of mineralocorticoid receptors raises BP more inAgtr1a(-/-)mice, AGTR1a is required for mineralocorticoid receptor stimulation to induce vascular remodeling and inflammation and endothelial dysfunction. PMID:27045029

  11. Human parainfluenza virus type 3 (HPIV3) induces production of IFNγ and RANTES in human nasal epithelial cells (HNECs)

    Lewandowska-Polak, Anna; Brauncajs, Małgorzata; Paradowska, Edyta; Jarzębska, Marzanna; Kurowski, Marcin; Moskwa, Sylwia; Leśnikowski, Zbigniew J.; Kowalski, Marek L

    2015-01-01

    Background Human parainfluenza virus type 3 (HPIV3), while infecting lower airway epithelial cells induces pneumonia and bronchiolitis in infants and children, and may lead to asthma exacerbations in children and adults. Respiratory viruses invading the airway epithelium activate innate immune response and induce inflammatory cytokine release contributing to the pathophysiology of upper and lower airway disorders. However, the effects of HPIV3 infection on nasal epithelial cells have not been...

  12. Akt activation induces hypertrophy without contractile phenotypic maturation in airway smooth muscle

    Ma, Lan; Brown, Melanie; Kogut, Paul; Serban, Karina; Li, Xiaojing; McConville, John; Chen, Bohao; Bentley, J. Kelley; Hershenson, Marc B.; Dulin, Nickolai; Solway, Julian; Camoretti-Mercado, Blanca

    2011-01-01

    Airway smooth muscle (ASM) hypertrophy is a cardinal feature of severe asthma, but the underlying molecular mechanisms remain uncertain. Forced protein kinase B/Akt 1 activation is known to induce myocyte hypertrophy in other muscle types, and, since a number of mediators present in asthmatic airways can activate Akt signaling, we hypothesized that Akt activation could contribute to ASM hypertrophy in asthma. To test this hypothesis, we evaluated whether Akt activation occurs naturally within...

  13. Survivin S81A Enhanced TRAIL's Activity in Inducing Apoptosis

    Ferry Sandra

    2010-12-01

    Full Text Available BACKGROUND: Survivin is rarely expressed in normal healthy adult tissues, however, it is upregulated in the majority of cancers. Survivin, which belongs to IAPs family, has been widely reported to protect cells from apoptosis by inhibiting caspases pathway. Survivin’s mitotic activity is modulated by many kinases, and its phosphor status can also influence its ability to inhibit apoptosis. There are several important survivin’s phosphorylation sites, such as S20 and T34. We have continued our investigation on other potential survivin’s phosphorylation sites that could be important site for regulating survivin’s cyto-protection. METHODS: By assuming that S81 could be a potential target to modify activity of survivin, wild-type survivin (Survivin, antisense survivin (Survivin-AS, mutated-survivin Thr34Ala (Survivin-T34A and mutated-survivin Ser81Ala (Survivin-S81A were constructed and inserted into pMSCV-IRES-GFP vector with cytomegalovirus (CMV promoter. Each retroviral product was produced in BOSC23 cells. LY294002 pretreatment and TRAIL treatment along with infection of retroviral products were performed in murine fibrosarcoma L929 cells. For analysis, flow cytometric apoptosis assay and western blot were performed. RESULTS: In our present study, survivin for providing cytoprotection was regulated by PI3K. The results showed that LY294002, an inhibitor of PI3K, effectively suppressed survivin-modulated cytoprotection in a TRAIL-induced apoptotic model. In addition, mutated survivin S81A showed marked suppression on survivin’s cytoprotection. Along with that, TRAIL’s apoptotic activity was enhanced for inducing apoptosis. CONCLUSIONS: We suggested that survivin could inhibit apoptosis through PI3K and S81A could be another potential target in order to inhibit Survivin-modulated cytoprotection as well as to sensitize efficacy of TRAIL or other related apoptotic inducers. KEYWORDS: apoptosis, survivin, TRAIL, S81A, L929, LY294002.

  14. Daily physical activity and type 2 diabetes: A review.

    Hamasaki, Hidetaka

    2016-06-25

    Physical activity improves glycemic control and reduces the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes (T2D). Moderate to vigorous physical activity is recommended to manage T2D; however, patients with T2D can be physically weak, making it difficult to engage in the recommended levels of physical activity. Daily physical activity includes various activities performed during both occupational and leisure time such as walking, gardening, and housework that type 2 diabetic patients should be able to perform without considerable physical burden. This review focuses on the association between daily physical activity and T2D. Walking was the most common form of daily physical activity, with numerous studies demonstrating its beneficial effects on reducing the risk of T2D, CVD, and mortality. Walking for at least 30 min per day was shown to reduce the risk of T2D by approximately 50%. Additionally, walking was associated with a reduction in mortality. In contrast, evidence was extremely limited regarding other daily physical activities such as gardening and housework in patients with T2D. Recent studies have suggested daily physical activity, including non-exercise activity thermogenesis, to be favorably associated with metabolic risks and mortality. However, well-designed longitudinal studies are warranted to elucidate its effects on overall health. PMID:27350847

  15. Redifferentiation of human hepatoma cells (SMMC-7721) induced by two new highly oxygenated bisabolane-type sesquiterpenes

    Ruidong Miao; Juan Wei; Q I Zhang; Venkateswara Sajja; Jinbo Yang; Qin Wang

    2008-12-01

    Bisabolane-type sesquiterpenes are a class of biologically active compounds that has antitumour, antifungal, antibacterial, antioxidant and antivenom properties. We investigated the effect of two new highly oxygenated bisabolane-type sesquiterpenes (HOBS) isolated from Cremanthodium discoideum (C. discoideum) on tumour cells. Our results showed that HOBS induced morphological differentiation and reduced microvilli formation on the cell surface in SMMC-7721 cells. Flow cytometry analysis demonstrated that HOBS could induce cell-cycle arrest in the G1 phase. Moreover, HOBS was able to increase tyrosine--ketoglutarate transaminase activity, decrease -foetoprotein level and -glutamyl transferase activity. In addition, we found that HOBS inhibited the anchorage-independent growth of SMMC-7721 cells in a dose-dependent manner. Taken together, all the above observations indicate that HOBS might be able to normalize malignant SMMC-7721 cells by inhibiting cell proliferation and inducing redifferentiation.

  16. Hyaluronic acid induces activation of the κ-opioid receptor.

    Barbara Zavan

    Full Text Available INTRODUCTION: Nociceptive pain is one of the most common types of pain that originates from an injury involving nociceptors. Approximately 60% of the knee joint innervations are classified as nociceptive. The specific biological mechanism underlying the regulation of nociceptors is relevant for the treatment of symptoms affecting the knee joint. Intra-articular administration of exogenous hyaluronic acid (HA in patients with osteoarthritis (OA appears to be particularly effective in reducing pain and improving patient function. METHODS: We performed an in vitro study conducted in CHO cells that expressed a panel of opioid receptors and in primary rat dorsal root ganglion (DRG neurons to determine if HA induces the activation of opioid peptide receptors (OPr using both aequorin and the fluorescent dye Fura-2/AM. RESULTS: Selective agonists and antagonists for each OPr expressed on CHO cells were used to test the efficacy of our in vitro model followed by stimulation with HA. The results showed that HA induces stimulatory effects on the κ receptor (KOP. These effects of HA were also confirmed in rat DRG neurons, which express endogenously the OPr. CONCLUSIONS: HA activates the KOP receptor in a concentration dependent manner, with a pEC(50 value of 7.57.

  17. Solar-Type Activity in Main-Sequence Stars

    Gershberg, Roald E

    2005-01-01

    Solar-type activity over the whole range of the electromagnetic spectrum is a phenomenon inherent in the majority of low- and moderate-mass main sequence stars. In this monograph observational results are summarized in a systematic and comprehensive fashion. The analysis of the various manifestations of such stellar activity leads to the identification of these phenomena with macroscopic non-linear processes in a magnetized plasma. Comparative study of flare stars and the Sun has become increasingly fruitful and is presently an active field of research involving stellar and solar physicists, experts in plasma physics and high-energy astrophysicists. This book will provide them with both an introduction and overview of observational results from the first optical photometry and spectroscopy, from the satellite telescopes International Ultraviolet Explorer to Hubble Space Telescope, XMM-Newton and Chandra, as well as with the present physical interpretation of solar-type activity in main sequence stars. Gershbe...

  18. Aging. Aging-induced type I interferon signaling at the choroid plexus negatively affects brain function

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M.; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2016-01-01

    Age-associated cognitive decline is affected by factors produced inside and outside the brain. We found in aged mice and humans, that the choroid plexus (CP), an epithelial interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent expression profile, often associated with anti-viral responses. This signature was induced by brain-derived signals present in the cerebrospinal fluid of aged mice. Blocking IFN-I signaling within the brain of cognitively-impaired aged mice, using IFN-I receptor neutralizing antibody, led to partial restoration of cognitive function and hippocampal neurogenesis, and reestablished IFN-II-dependent CP activity, lost in aging. Our data identify an aging-induced IFN-I signature at the CP, and demonstrate its negative influence on brain function, thereby suggesting a potential target for therapeutic intervention for age-related cognitive decline. PMID:25147279

  19. Classification of types of stuttering symptoms based on brain activity.

    Jing Jiang

    Full Text Available Among the non-fluencies seen in speech, some are more typical (MT of stuttering speakers, whereas others are less typical (LT and are common to both stuttering and fluent speakers. No neuroimaging work has evaluated the neural basis for grouping these symptom types. Another long-debated issue is which type (LT, MT whole-word repetitions (WWR should be placed in. In this study, a sentence completion task was performed by twenty stuttering patients who were scanned using an event-related design. This task elicited stuttering in these patients. Each stuttered trial from each patient was sorted into the MT or LT types with WWR put aside. Pattern classification was employed to train a patient-specific single trial model to automatically classify each trial as MT or LT using the corresponding fMRI data. This model was then validated by using test data that were independent of the training data. In a subsequent analysis, the classification model, just established, was used to determine which type the WWR should be placed in. The results showed that the LT and the MT could be separated with high accuracy based on their brain activity. The brain regions that made most contribution to the separation of the types were: the left inferior frontal cortex and bilateral precuneus, both of which showed higher activity in the MT than in the LT; and the left putamen and right cerebellum which showed the opposite activity pattern. The results also showed that the brain activity for WWR was more similar to that of the LT and fluent speech than to that of the MT. These findings provide a neurological basis for separating the MT and the LT types, and support the widely-used MT/LT symptom grouping scheme. In addition, WWR play a similar role as the LT, and thus should be placed in the LT type.

  20. Regulation of programmed cell death by plasminogen activator inhibitor type 1 (PAI-1)

    Lademann, Ulrik Axel; Rømer, Maria Unni Koefoed

    2008-01-01

    numbers of reports suggest that PAI-1 also can regulate programmed cell death (PCD) in cancer cells and normal cells. A number of reports suggest that PAI-1 can inhibit PCD through its pro-adhesive/anti-proteolytic property whereas other reports suggest that PAI-1 induces PCD through its anti......-adhesive property.Furthermore,it has been suggested that PAI-1 can either induce or inhibit PCD though activation of cell signalling pathways.This review will focus on the regulation of programmed cell death by PAI-1 in both normal cells and cancer cells.......Elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with poor prognosis in cancer. An explanation to the elevated levels of PAI-1 could be a protective response to the increased proteolytic activity, caused by elevated levels of urokinase- type plasminogen activator (u...

  1. Solar-Type Activity: Epochs of Cycle Formation

    Katsova, M M; Livshits, M A

    2015-01-01

    The diagram of indices of coronal and chromospheric activity allowed us to reveal stars where solar-type activity appears and regular cycles are forming. Using new consideration of a relation between coronal activity and the rotation rate, together with new data on the ages of open clusters, we estimate the age of the young Sun corresponding to the epoch of formation of its cycle. The properties of the activity of this young Sun, with an age slightly older than one billion years, are briefly discussed. An analysis of available data on the long-term regular variability of late-type stars leads to the conclusion that duration of a cycle associated with solar-type activity increases with the deceleration of the stellar rotation; i.e., with age. New data on the magnetic fields of comparatively young G stars and changes in the role of the large-scale and the local magnetic fields in the formation of the activity of the young Sun are discussed. Studies in this area aim to provide observational tests aimed at identi...

  2. Specific MAPK inhibitors prevent hyperglycemia-induced renal diseases in type 1 diabetic mouse model.

    Hong, Zhe; Hong, Zongyuan; Wu, Denglong; Nie, Hezhongrong

    2016-08-01

    Mitogen-activated protein kinase (MAPK) and renin-angiotensin system (RAS) play critical roles in the process of renal diseases, but their interaction has not been comprehensively discussed. In the present studies, we investigated the renoprotective effects of MPAK inhibitors on renal diseases in type 1 diabetic mouse model, and clarify the crosstalk among MAPK signaling. Type 1 diabetic mouse model was established in male C57BL/6 J mice, and treated with or without 10 mg/kg MAPK blockers, including ERK inhibitor PD98059, p38 inhibitor SB203850, and JNK inhibitor SP600125 for four weeks. Hyperglycemia induced renal injuries, but treating them with MAPK inhibitors significantly decreased glomerular volume and glycogen in renal tissues. Although slightly changed body weight and fasting blood glucose levels, MAPK inhibitors attenuated blood urea nitrogen, urea protein, and microalbuminuria. Administration also reduced the diabetes-induced RAS activation, including angiotensin II converting enzyme (c) and Ang II, which contributed to its renal protective effects in the diabetic mice. In addition, the anti-RAS of MAPK inhibitor treatment markedly reduced gene expression of tumor necrosis factor-α, interleukin-6, and inducible nitric oxide synthase, fibrotic accumulation, and transforming growth factor-β1 levels in renal tissues. Furthermore, chemical inhibitors and genetic siRNA results identified the crosstalk among the three MAPK signaling, and proved JNK signaling played a critical role in MAPK-mediated ACE pathway in hyperglycemia state. Collectively, these results support the therapeutic effects of MAPK-specific inhibitors, especially JNK inactivation, on hyperglycemia-induced renal damages. PMID:27389030

  3. The interaction between bovine herpesvirus type 1 and activated bovine T lymphocytes.

    Griebel, P J; Ohmann, H B; Lawman, M J; Babiuk, L A

    1990-02-01

    The interaction between activated bovine T lymphocytes (BTLs) and bovine herpesvirus type 1 (BHV-1) was investigated. BHV-1 infection of BTLs reduced the amplitude of recombinant bovine interleukin 2-induced proliferative responses. This decreased proliferation was caused by a virus-induced lymphocytolysis which was dependent on viable virus and was not inhibited by recombinant bovine interferon-alpha I1. Furthermore, lymphocytolysis was not associated with virus replication or with the synthesis of detectable levels of viral proteins. Electron microscopic examination of virus-infected cells revealed that lymphocytolysis was characterized by early nuclear disintegration resembling apoptosis. These observations suggest that activated T cells, localized at the site of BHV-1 infection, may be susceptible to virus-induced cytolysis. PMID:2155290

  4. Hydrogen sulfide raises cytosolic calcium in neurons through activation of L-type Ca2+ channels.

    García-Bereguiaín, Miguel Angel; Samhan-Arias, Alejandro Khalil; Martín-Romero, Francisco Javier; Gutiérrez-Merino, Carlos

    2008-01-01

    Hydrogen sulfide (H(2)S) concentration can be maintained in cell cultures within the range reported for rat brain by repetitive pulses of sodium hydrogen sulfide. Less than 2 h exposure to H(2)S concentrations within 50 and 120 microM (i.e., within the upper segment of the reported physiological range of H(2)S in rat brain), produces a large shift of the intracellular calcium homeostasis in cerebellar granule neurons (CGN) in culture, leading to a large and sustained increase of cytosolic calcium concentration. Only 1 h exposure to H(2)S concentrations within 100 and 300 microM raises intracellular calcium to the neurotoxic range, with nearly 50% cell death after 2 h. L-type Ca(2+) channels antagonists nimodipine and nifedipine block both the H(2)S-induced rise of cytosolic calcium and cell death. The N-methyl-D-aspartate receptor antagonists (+)-MK-801 and DL-2-amino-5-phosphonovaleric acid afforded a nearly complete protection against H(2)S-induced CGN death and largely attenuated the rise of cytosolic calcium. Thus, H(2)S-induced rise of cytosolic calcium eventually reaches the neurotoxic cytosolic calcium range, leading to glutamate-induced excitotoxic CGN death. The authors conclude that H(2)S is a major modulator of calcium homeostasis in neurons as it induces activation of Ca(2+) entry through L-type Ca(2+) channels, and thereby of neuronal activity. PMID:17956188

  5. Baicalein selectively induces apoptosis in activated lymphocytes and ameliorates concanavalin a-induced hepatitis in mice.

    Yan Zhang

    Full Text Available BACKGROUND: Insufficient apoptosis in activated lymphocytes contributes to the development of autoimmune hepatitis (AIH. Baicalein (BE, a flavonoid originally isolated from the root of Scutellaria baicalensis Georgi, possesses anti-inflammatory properties. However, whether BE can selectively induce apoptosis in activated lymphocytes and exert therapeutic effect on AIH has not been studied. METHODOLOGY/PRINCIPAL FINDINGS: The pro-apoptotic properties of BE were evaluated in vitro on different types of immune cells, and in vivo effects of BE were examined in a murine model of Concanavalin A (Con A-induced hepatitis. In vitro treatment with BE resulted in a higher increase in the level of apoptosis in Con A-stimulated murine splenocytes, Con A-stimulated CD3(+ splenocytes, lipopolysaccharide (LPS-stimulated CD19(+ splenocytes, and phorbol 12-myristate 13-acetate/ionomycin-stimulated Jurkat T cells, compared with that in unstimulated naïve ones. Murine bone marrow-derived dentritic cells, peritoneal macrophages, and RAW264.7 cells, either stimulated with LPS or unstimulated, were all insensitive to the BE-induced apoptosis. BE treatment also led to a loss of mitochondrial membrane potential, an increase of cytochrome c release from mitochondria to the cytosol, a decrease in the ratio of Bcl-2/Bax, and activation of caspase-9,-3 in Con A-stimulated CD3(+ splenocytes and LPS-stimulated CD19(+ splenocytes, while showing no impact on Fas/FasL expressions and caspase-8 activation. In vivo administration of BE alleviated Con A-induced liver injury, suppressed serum level of TNF-α and IFN-γ, and reduced liver infiltration of mononuclear cells (MNCs. Furthermore, BE treatment increased the incidences of apoptosis in liver-infiltrating MNCs and splenocytes, as well as in CD3(+ and CD19(+ splenocytes. When liver MNCs and splenocytes from BE-treated mice were cultured in vitro for 24 h, they exhibited marked increase in apoptosis compared to vehicle

  6. Efficient Mating-Type Switching in Candida glabrata Induces Cell Death

    Boisnard, Stéphanie; Zhou Li, Youfang; Arnaise, Sylvie; Sequeira, Gregory; Raffoux, Xavier; Enache-Angoulvant, Adela; Bolotin-Fukuhara, Monique; Fairhead, Cécile

    2015-01-01

    Candida glabrata is an apparently asexual haploid yeast that is phylogenetically closer to Saccharomyces cerevisiae than to Candida albicans. Its genome contains three MAT-like cassettes, MAT, which encodes either MATa or MATalpha information in different strains, and the additional loci, HML and HMR. The genome also contains an HO gene homolog, but this yeast has never been shown to switch mating-types spontaneously, as S. cerevisiae does. We have recently sequenced the genomes of the five species that, together with C. glabrata, make up the Nakaseomyces clade. All contain MAT-like cassettes and an HO gene homolog. In this work, we express the HO gene of all Nakaseomyces and of S. cerevisiae in C. glabrata. All can induce mating-type switching, but, despite the larger phylogenetic distance, the most efficient endonuclease is the one from S. cerevisiae. Efficient mating-type switching in C. glabrata is accompanied by a high cell mortality, and sometimes results in conversion of the additional cassette HML. Mortality probably results from the cutting of the HO recognition sites that are present, in HML and possibly HMR, contrary to what happens naturally in S. cerevisiae. This has implications in the life-cycle of C. glabrata, as we show that efficient MAT switching is lethal for most cells, induces chromosomal rearrangements in survivors, and that the endogenous HO is probably rarely active indeed. PMID:26491872

  7. ROS-mediated glucose metabolic reprogram induces insulin resistance in type 2 diabetes.

    Dong, Kelei; Ni, Hua; Wu, Meiling; Tang, Ziqing; Halim, Michael; Shi, Dongyun

    2016-08-01

    Oxidative stress is known to contribute to insulin resistance in diabetes, however the mechanism is not clear. Here we show that reactive oxygen species (ROS) could reprogram the glucose metabolism through upregulating the pentose pathway so as to induce insulin resistance in type 2 diabetes (T2DM). By using streptozotocin-high fat diet (STZ-HFD) induced T2DM in rats, we show that diabetic rats exhibited high level of oxidative stress accompanied with insulin resistance. Hypoxia inducible factor (HIF-1α) protein expression as well as its downstream target glucokinase (GK), were upregulated; The glycogen synthesis increased accordingly; However the glycolysis was inhibited as indicated by decreased phosphofructokinase-1 (PFK-1), pyruvate kinase (PK), phospho-PFK-2/PFK-2 (p-PFK-2/PFK-2) ratio, lactate dehydrogenase (LDH) and pyruvate dehydrogenase kinase (PDK); Pyruvate dehydrogenase (PDH) which promotes pyruvate to generate acetyl-CoA declined as well. While phospho-acetyl-CoA carboxylase/acetyl-CoA carboxylase (p-ACC/ACC) ratio increased, meaning that lipid beta-oxidation increased. The pentose pathway was activated as indicated by increased G6PD activity and NADPH level. Our results suggest that diabetic rats countervail ROS stress through increasing pentose pathway, and reprogram the energy metabolic pathway from glycolysis into lipid oxidation in order to compensate the ATP requirement of the body, which causes insulin resistance. PMID:27207834

  8. Activity trends in young solar-type stars

    Lehtinen, Jyri; Hackman, Thomas; Kajatkari, Perttu; Henry, Gregory W

    2015-01-01

    We apply the Continuous Period Search (CPS) time series analysis method on Johnson B and V band photometry of 21 young and active solar-type, collected over 16 to 27 years and characterize the behaviour of their activity. Using the CPS method, differential rotation could be estimated from the observed variations of the photometric rotation period. Active longitudes were retrieved by applying a non-parametric period search on the light curve minimum epochs, and activity cycles by applying a secondary period search on the modelled light curve mean and amplitude values. We supplemented the time series results by calculating new $\\log{R'_{\\rm HK}}$ emission indices for the stars from high resolution spectroscopy. The measurements of the photometric rotation period variations point to a trend of increasing differential rotation coefficients towards longer rotation periods but do not reveal any dependence from the effective temperature of the stars. The secondary period searches revealed activity cycles in 18 of th...

  9. [Antioxidant activity of different types of red grape wines].

    Ageeva, N M; Markosov, V A; Avidzba, A M; Ogay, Yu A

    2016-01-01

    This article represented the data about antioxidant activity in the red table and liqueurfaults, prepared from the types of grapes of Cabernet, Merlot and Saperavi. The antioxidant activity of faults in the conversion to TROLOX, the synthetic analog of gallic acid, was determined by voltammetric method. The determination of antioxidant activity was conducted in the young faults (through 2 month after the completion of fermentation) and through half a year the storage without the air inlet. It has been established that the value of antioxidant activity depended on the type of grapes and technology of the production of wine. It was shown that the addition of ethyl alcohol in the production of wines such as Cahors ensured an increase in the extraction of phenol connections from the skin of grapes. This lead to an increase of the antioxidant activity in the Cahors wines in the comparison with the table wine. During the storage of faults the value of antioxidant activity decreased. In the fault cahors wine it remained at the higher level. PMID:27228712

  10. Photocatalytic activity of glass ceramics containing Nasicon-type crystals

    Graphical abstract: Display Omitted Highlights: ► Glass ceramics containing Nasicon-type crystals were prepared. ► The glass ceramics showed photocatalytic activity under UV irradiation. ► Higher activity was observed in the MgTi4(PO4)6- and CaTi4(PO4)6-containing glass ceramics. -- Abstract: Glass ceramics were prepared by heat-treating MO–TiO2–P2O5 (M = Mg, Ca, Sr and Ba) and R2O–TiO2–P2O5–SiO2 (R = Li, Na and K) glasses, and their photocatalytic activity was investigated. The crystalline phases precipitated in the glasses were only Nasicon-type crystals, MTi4(PO4)6 or RTi2(PO4)3. Decomposition experiments of both methylene blue (MB) and acetaldehyde showed that the glass ceramics exhibited effective photocatalytic activity. The activity did not depend on the radius of the M2+ or R+ ion, and higher activity was observed in the MgTi4(PO4)6 and CaTi4(PO4)6 precipitated glass ceramics.

  11. Eye Typing using Markov and Active Appearance Models

    Hansen, Dan Witzner; Hansen, John Paulin; Nielsen, Mads;

    2002-01-01

    multi-modal interactions based on video tracking systems. Robust methods are needed to track the eyes using web cameras due to the poor image quality. A real-time tracking scheme using a mean-shift color tracker and an Active Appearance Model of the eye is proposed. It is possible from this model to......We propose a non-intrusive eye tracking system intended for the use of everyday gaze typing using web cameras. We argue that high precision in gaze tracking is not needed for on-screen typing due to natural language redundancy. This facilitates the use of low-cost video components for advanced...

  12. Vine type mutant induced in Vigna mungo L

    Full text: Dry seeds of the black gram variety T9 were irradiated with 10-30 kR gamma rays followed by treatment with 0.25% EMS. Several vine type mutants were obtained, showing 2.5 times increase in final plant height. Pollen fertility was normal, maturity period unaffected. Segregation ratio suggests monogenic recessive inheritance of the vine type. (author)

  13. [Functional activity of lymphoblastoid cells infected by human adenovirus type 2 and Epstein-Barr virus].

    Povnitsa, O Iu; Diachenko, N S; Nosach, L N; Olevinskaia, Z M; Zhovnovataia, V L; Polishchuk, V N; Spivak, N Ia

    2005-01-01

    The paper deals with the influence of the adenovirus (Ad) and Epstein-Barr virus (EBV) on functional activity of lymphocytes, in particular, the production of alpha- and gamma-interferons, tumor necrosis factor (TNF) in conditions of mono- or double infection of B- and T-phenotype (CEM) lymphoblastoid cells. It is shown, that Ad, EBV or both viruses induce high enough levels of interferon on both lines of cells and in control epithelial cells. The lymphoblastoid cells infected by viruses deep ability to synthesize alpha- and gamma-interferons under the influence of the corresponding inducers (Newcastle disease virus and hemagglutinine). Nevertheless, the levels of their formation are not high. Rather high parameters of activity of the tumor necrosis factor (TNF) were revealed during a day in the initial B95-8 cells and superinfected Ad after the effect of LPS of E. coli. Their activity in CEM cells also did not depend on the infection type. PMID:16018208

  14. Activation of the Farnesoid X Receptor Provides Protection against Acetaminophen-Induced Hepatic Toxicity

    Lee, Florence Ying; de Aguiar Vallim, Thomas Quad; Chong, Hansook Kim; Zhang, Yanqiao; Liu, Yaping; Jones, Stacey A.; Osborne, Timothy F.; Edwards, Peter A.

    2010-01-01

    The nuclear receptor, farnesoid X receptor (FXR, NR1H4), is known to regulate cholesterol, bile acid, lipoprotein, and glucose metabolism. In the current study, we provide evidence to support a role for FXR in hepatoprotection from acetaminophen (APAP)-induced toxicity. Pharmacological activation of FXR induces the expression of several genes involved in phase II and phase III xenobiotic metabolism in wild-type, but not Fxr−/− mice. We used chromatin immunoprecipitation-based genome-wide resp...

  15. Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

    Groneberg David A

    2008-02-01

    Full Text Available Abstract Background Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity. Methods The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique. Results Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity. Conclusion Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.

  16. Altered Erythrocyte Glycolytic Enzyme Activities in Type-II Diabetes.

    Mali, Aniket V; Bhise, Sunita S; Hegde, Mahabaleshwar V; Katyare, Surendra S

    2016-07-01

    The activity of enzymes of glycolysis has been studied in erythrocytes from type-II diabetic patients in comparison with control. RBC lysate was the source of enzymes. In the diabetics the hexokinase (HK) activity increased 50 % while activities of phosphoglucoisomerase (PGI), phosphofructokinase (PFK) and aldolase (ALD) decreased by 37, 75 and 64 % respectively but were still several folds higher than that of HK. Hence, it is possible that in the diabetic erythrocytes the process of glycolysis could proceed in an unimpaired or in fact may be augmented due to increased levels of G6P. The lactate dehydrogenase (LDH) activity was comparatively high in both the groups; the diabetic group showed 85 % increase. In control group the HK, PFK and ALD activities showed strong positive correlation with blood sugar level while PGI activity did not show any correlation. In the diabetic group only PFK activity showed positive correlation. The LDH activity only in the control group showed positive correlation with marginal increase with increasing concentrations of glucose. PMID:27382204

  17. Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

    Kumagai, Kazuyoshi; Lewandowski, Ryan; Jackson-Humbles, Daven N; Li, Ning; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R

    2016-06-01

    Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure. PMID:26559808

  18. Acrylamide inhibits nerve sprouting induced by botulinum toxin type A

    Hong Jiang; Yi Xiang; Xingyue Hu; Huaying Cai

    2014-01-01

    Botulinum toxin type A is a potent muscle relaxant that blocks the transmission and release of acetylcholine at the neuromuscular junction. Intramuscular injection of botulinum toxin type A has served as an effective and safe therapy for strabismus and focal dystonia. However, muscular weakness is temporary and after 3-4 months, muscle strength usually recovers because function-al recovery is mediated by nerve sprouting and reconstruction of the neuromuscular junction. Acrylamide may produce neurotoxic substances that cause retrograde necrotizing neuropathy and inhibit nerve sprouting caused by botulinum toxin type A. This study investigated whether acrylamide inhibits nerve sprouting after intramuscular injection of botulinum toxin type A. A tibial nerve sprouting model was established through local injection of botulinum toxin type A into the right gastrocnemius muscle of Sprague-Dawley rats. Following intramuscular injection, rats were given intraperitoneal injection of 3%acrylamide every 3 days for 21 days. Nerve sprout-ing appeared 2 weeks after intramuscular injection of botulinum toxin type A and single-fiber electromyography revealed abnormal conduction at the neuromuscular junction 1 week after intra-muscular injection of botulinum toxin type A. Following intraperitoneal injection of acrylamide, the peak muscle ifber density decreased. Electromyography jitter value were restored to normal levels 6 weeks after injection. This indicates that the maximal decrease in ifber density and the time at which functional conduction of neuromuscular junction was restored were delayed. Addition-ally, the increase in tibial nerve ifbers was reduced. Acrylamide inhibits nerve sprouting caused by botulinum toxin type A and may be used to prolong the clinical dosage of botulinum toxin type A.

  19. Gamma ray induced electrical conductivity in bisphenol-A type epoxy resin and polyethylene terephthalate

    The insulation materials to support magnets for nuclear fusion reactors are exposed to high energy neutron beam and the gamma ray due to the accompanying induced radio activity through blankets or radiation shields. In such materials, radiation-induced conduction (RIC) is a problem, which occurs due to the charged particles generated in the insulation materials during irradiation. As one of such materials, use of epoxy composite material is expected, but its RIC has been scarcely measured. An approach to measure the wave form of transient current (or electric charge) caused by irradiating the radiation pulses of nano-second order to the materials has been developed. This paper reports the results of having measured RIC in bisphenol-A type epoxy resin at the electric field from 1 x 104 to 3 x 105 V/cm and γ dose rate from 9 x 103 to 9 x 105 R/h over the temperature range of -170 deg. C to +110 deg. C. The RIC of polyethylene terephthalate (PET) was also measured in the same regions, whose molecular structure is comparatively similar to the bisphenol-A type epoxy resin, and of which the fundamental processes for RIC have been clarified pretty well. The radiation sources of 4.3 kCi 60Co of NAIG and 45 kCi 60Co of JAERI were used. The experimental circuits and the cryostat are described, then as for the results, explanation and discussion are given to the characteristics of induced current, dependence on dose rate and dependence on temperature of RIC conductivity. The process of capturing carrier in deep traps seems to be dominant in the bisphenol-A type epoxy resin, similarly to that of PET. (Wakatsuki, Y.)

  20. Sepsis-Induced Inflammation Is Exacerbated in an Animal Model of Type 2 Diabetes

    Jacob, Asha; Steinberg, Marissa L.; Yang, Juntao; Dong, Weifeng; Ji, Youxin; Wang, Ping

    2008-01-01

    Hyperglycemia is common in critically ill patients and pronounced hyperglycemia may lead to complications which include severe infections, polyneuropathy, multiple organ failure and death in such patients. Sustained hyperglycemia is generally observed in patients with Type 2 diabetes. To explore sepsis-induced inflammation in Type 2 diabetes, polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in the Goto-Kakizaki (GK) rat, a spontaneous animal model of Type 2 diabetes. The ...

  1. Graphene active plasmonic metamaterials for new types of terahertz lasers

    Otsuji, Taiichi; Watanabe, Takayuki; Satou, Akira; Popov, Vyacheslav; Ryzhii, Victor

    2013-05-01

    This paper reviews recent advances in graphene active plasmonic metamaterials for new types of terahertz lasers. We theoretically discovered that when the population of Dirac Fermionic carriers in graphene are inverted by optical or electrical pumping the excitation of graphene plasmons by the THz photons results in propagating surface plasmon polaritons with giant gain in a wide THz range. Furthermore, when graphene is patterned in a micro- or nano-ribbon array by grating gate metallization, the structure acts as an active plasmonic metamaterial, providing a super-radiant plasmonic lasing with giant gain at the plasmon modes in a wide THz frequency range.

  2. Physical activity and type 1 diabetes: time for a rewire?

    Colberg, Sheri R; Laan, Remmert; Dassau, Eyal; Kerr, David

    2015-05-01

    While being physically active bestows many health benefits on individuals with type 1 diabetes, their overall blood glucose control is not enhanced without an effective balance of insulin dosing and food intake to maintain euglycemia before, during, and after exercise of all types. At present, a number of technological advances are already available to insulin users who desire to be physically active with optimal blood glucose control, although a number of limitations to those devices remain. In addition to continued improvements to existing technologies and introduction of new ones, finding ways to integrate all of the available data to optimize blood glucose control and performance during and following exercise will likely involve development of "smart" calculators, enhanced closed-loop systems that are able to use additional inputs and learn, and social aspects that allow devices to meet the needs of the users. PMID:25568144

  3. Methylphenidate Actively Induces Emergence from General Anesthesia

    Solt, Ken; Cotten, Joseph F.; Cimenser, Aylin; Wong, Kin F.K.; Chemali, Jessica J.; Brown, Emery N.

    2011-01-01

    Background: Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study, the authors tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane general anesthesia. Methods: Using adult rats, the authors tested the effect of intravenous methylphenidate on time to emergence...

  4. Human-induced soil degradation activities

    Oldeman L.R.; Van Baren J.H. V.

    1998-01-01

    Soil degradation is occurring over vast areas. The GLASOD and ASSOD projects reflect the present status of human-induced soil degradation and its impact on food productivity related to productivity changes observed in the recent past. However, there is a great need for well-documented, reliable soil information and other related data at national and regional levels to better understand and qualify the impact of changing soil conditions or biomass production.

  5. Human immunodeficiency virus-like particles activate multiple types of immune cells

    The rapid spread of human immunodeficiency virus (HIV) worldwide makes it a high priority to develop an effective vaccine. Since live attenuated or inactivated HIV is not likely to be approved as a vaccine due to safety concerns, HIV virus like particles (VLPs) offer an attractive alternative because they are safe due to the lack of a viral genome. Although HIV VLPs have been shown to induce humoral and cellular immune responses, it is important to understand the mechanisms by which they induce such responses and to improve their immunogenicity. We generated HIV VLPs, and VLPs containing Flt3 ligand (FL), a dendritic cell growth factor, to target VLPs to dendritic cells, and investigated the roles of these VLPs in the initiation of adaptive immune responses in vitro and in vivo. We found that HIV-1 VLPs induced maturation of dendritic cells and monocyte/macrophage populations in vitro and in vivo, with enhanced expression of maturation markers and cytokines. Dendritic cells pulsed with VLPs induced activation of splenocytes resulting in increased production of cytokines. VLPs containing FL were found to increase dendritic cells and monocyte/macrophage populations in the spleen when administered to mice. Administration of VLPs induced acute activation of multiple types of cells including T and B cells as indicated by enhanced expression of the early activation marker CD69 and down-regulation of the homing receptor CD62L. VLPs containing FL were an effective form of antigen in activating immune cells via dendritic cells, and immunization with HIV VLPs containing FL resulted in enhanced T helper type 2-like immune responses

  6. Methodology and conclusions of activation calculations of WWER-440 type nuclear power plants

    Highlights: • Activation calculation of two WWER-440 type nuclear power plants. • Detailed description of the applied activation calculation methodology. • Graphical results for total activity and waste index categorization. • General conclusions for activation applicable in the case of PWR reactors. - Abstract: Activation calculations for two nuclear power plants of WWER-440 type have been performed by the authors in order to assist the decommissioning planning by assessing the radioactive inventory present at the time of and at different times after the final shutdown. According to related international literature and studies performed earlier by the authors, considering the activity more than 99% of this inventory is concentrated in the materials directly surrounding the reactor core, where the predominant evolution of radionuclides is generated by neutron induced nuclear reactions. In order to obtain the highest possible accuracy in modelling, three-dimensional Monte Carlo neutron transport calculations were performed. Besides the methods and models applied to these analyses, the paper also summarizes the results that can be generally applied to such nuclear power plant types. At the time of shutdown, the total activity of the stainless steel components is about 6 × 1016 Bq and 1.3 × 1017 Bq for the two NPPs considered. The biological shielding concrete constitutes approximately 7 × 1013 Bq and 1.1 × 1014 Bq

  7. Acrylamide inhibits nerve sprouting induced by botulinum toxin type A

    Jiang, Hong; Xiang, Yi; Hu, XingYue; Cai, Huaying

    2014-01-01

    Botulinum toxin type A is a potent muscle relaxant that blocks the transmission and release of acetylcholine at the neuromuscular junction. Intramuscular injection of botulinum toxin type A has served as an effective and safe therapy for strabismus and focal dystonia. However, muscular weakness is temporary and after 3–4 months, muscle strength usually recovers because functional recovery is mediated by nerve sprouting and reconstruction of the neuromuscular junction. Acrylamide may produce n...

  8. Involvement of sphingosine in mitochondria-dependent Fas-induced apoptosis of type II Jurkat T cells.

    Cuvillier, O; Edsall, L; Spiegel, S

    2000-05-26

    Exposure to anti-Fas antibody in Jurkat cells (type II cells), which are characterized by a weak caspase-8 activation at the death-inducing signaling complex (DISC), induced a biphasic increase in ceramide levels. The early generation of ceramide preceded transient activation of acidic ceramidase and subsequent production of sphingosine, followed by cytochrome c release, activation of caspases-2, -3, -6, -7, -8, and -9, Bid cleavage, and a later sustained ceramide accumulation. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone inhibited early increases of ceramide and sphingosine, whereas overexpression of Bcl-x(L) had no effect, and both prevented the later sustained ceramide accumulation. Exogenous sphingosine, as well as cell-permeable C(2)-ceramide, induced cytochrome c release from mitochondria in a caspase-independent fashion leading to activation of caspase-9 and executioner caspases and, surprisingly, activation of the initiator caspase-8 and processing of its substrate Bid. These effects were also completely abolished by Bcl-x(L) overexpression. Our results suggest that sphingosine might also be involved in the mitochondria-mediated pathway of Fas-induced cell death in type II cells. PMID:10747891

  9. ACT-1000. Group activation cross-section library for WWER-1000 type reactors

    The ACT-1000, a problem-oriented library of group-averaged activation cross-sections for WWER-1000 type reactors, is based on evaluated microscopic cross-section data files. The ACT-1000 data library was designed for calculating induced activity for the main dose-generated nuclides contained in WWER-1000 structural materials. In preparing the ACT-1000 library, 47 group-averaged cross-section data for the 10-9-17.33 MeV energy range were used to calculate the spatial-energy neutron flux distribution. (author)

  10. Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid–type III polyketide synthase

    Austin, Michael B; Saito, Tamao; Bowman, Marianne E.; Haydock, Stephen; Kato, Atsushi; Moore, Bradley S.; Kay, Robert R.; Noel, Joseph P.

    2006-01-01

    Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two ~3,000-residue D. discoideum proteins, termed ‘steely’, as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid syntha...

  11. Adenosine-induced activation of esophageal nociceptors.

    Ru, F; Surdenikova, L; Brozmanova, M; Kollarik, M

    2011-03-01

    Clinical studies implicate adenosine acting on esophageal nociceptive pathways in the pathogenesis of noncardiac chest pain originating from the esophagus. However, the effect of adenosine on esophageal afferent nerve subtypes is incompletely understood. We addressed the hypothesis that adenosine selectively activates esophageal nociceptors. Whole cell perforated patch-clamp recordings and single-cell RT-PCR analysis were performed on the primary afferent neurons retrogradely labeled from the esophagus in the guinea pig. Extracellular recordings were made from the isolated innervated esophagus. In patch-clamp studies, adenosine evoked activation (inward current) in a majority of putative nociceptive (capsaicin-sensitive) vagal nodose, vagal jugular, and spinal dorsal root ganglia (DRG) neurons innervating the esophagus. Single-cell RT-PCR analysis indicated that the majority of the putative nociceptive (transient receptor potential V1-positive) neurons innervating the esophagus express the adenosine receptors. The neural crest-derived (spinal DRG and vagal jugular) esophageal nociceptors expressed predominantly the adenosine A(1) receptor while the placodes-derived vagal nodose nociceptors expressed the adenosine A(1) and/or A(2A) receptors. Consistent with the studies in the cell bodies, adenosine evoked activation (overt action potential discharge) in esophageal nociceptive nerve terminals. Furthermore, the neural crest-derived jugular nociceptors were activated by the selective A(1) receptor agonist CCPA, and the placodes-derived nodose nociceptors were activated by CCPA and/or the selective adenosine A(2A) receptor CGS-21680. In contrast to esophageal nociceptors, adenosine failed to stimulate the vagal esophageal low-threshold (tension) mechanosensors. We conclude that adenosine selectively activates esophageal nociceptors. Our data indicate that the esophageal neural crest-derived nociceptors can be activated via the adenosine A(1) receptor while the placodes

  12. Verification of a characterization method of the laser-induced selective activation based on industrial lasers

    Zhang, Yang; Hansen, Hans Nørgaard; Tang, Peter T.;

    2013-01-01

    In this article, laser-induced selective activation (LISA) for subsequent autocatalytic copper plating is performed by several types of industrial scale lasers, including a Nd:YAG laser, a UV laser, a fiber laser, a green laser, and a short pulsed laser. Based on analysis of all the laser-machine...

  13. Plasminogen activator inhibitor-1 polymers, induced by inactivating amphipathic organochemical ligands

    Pedersen, Katrine E; Einholm, Anja P; Christensen, Anni;

    2003-01-01

    compared with native PAI-1, the polymers exhibited an increased resistance to temperature-induced unfolding. Polymerization was associated with specific changes in patterns of digestion with non-target proteases. During incubation with urokinase-type plasminogen activator, the polymers were slowly...

  14. Transforming growth factor β1 induces the expression of collagen type I by DNA methylation in cardiac fibroblasts.

    Xiaodong Pan

    Full Text Available Transforming growth factor-beta (TGF-β, a key mediator of cardiac fibroblast activation, has a major influence on collagen type I production. However, the epigenetic mechanisms by which TGF-β induces collagen type I alpha 1 (COL1A1 expression are not fully understood. This study was designed to examine whether or not DNA methylation is involved in TGF-β-induced COL1A1 expression in cardiac fibroblasts. Cells isolated from neonatal Sprague-Dawley rats were cultured and stimulated with TGF-β1. The mRNA levels of COL1A1 and DNA methyltransferases (DNMTs were determined via quantitative polymerase chain reaction and the protein levels of collagen type I were determined via Western blot as well as enzyme-linked immunosorbent assay. The quantitative methylation of the COL1A1 promoter region was analyzed using the MassARRAY platform of Sequenom. Results showed that TGF-β1 upregulated the mRNA expression of COL1A1 and induced the synthesis of cell-associated and secreted collagen type I in cardiac fibroblasts. DNMT1 and DNMT3a expressions were significantly downregulated and the global DNMT activity was inhibited when treated with 10 ng/mL of TGF-β1 for 48 h. TGF-β1 treatment resulted in a significant reduction of the DNA methylation percentage across multiple CpG sites in the rat COL1A1 promoter. Thus, TGF-β1 can induce collagen type I expression through the inhibition of DNMT1 and DNMT3a expressions as well as global DNMT activity, thereby resulting in DNA demethylation of the COL1A1 promoter. These findings suggested that the DNMT-mediated DNA methylation is an important mechanism in regulating the TGF-β1-induced COL1A1 gene expression.

  15. Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense Pathways in Rat Alveolar Type II Pneumocytes

    Alexis Valauri-Orton

    2015-01-01

    Full Text Available Dichloroacetate (DCA is a water purification byproduct that is known to be hepatotoxic and hepatocarcinogenic and to induce peripheral neuropathy and damage macrophages. This study characterizes the effects of the haloacetate on lung cells by exposing rat alveolar type II (L2 cells to 0–24 mM DCA for 6–24 hours. Increasing DCA concentration and the combination of increasing DCA concentration plus longer exposures decrease measures of cellular health. Length of exposure has no effect on oxidative stress biomarkers, glutathione, SOD, or CAT. Increasing DCA concentration alone does not affect total glutathione or its redox ratio but does increase activity in the SOD/CAT oxidative stress defense pathway. These data suggest that alveolar type II cells rely on SOD and CAT more than glutathione to combat DCA-induced stress.

  16. Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in macrophages.

    Yun Jeong Kim

    Full Text Available Botulinum neurotoxin type A (BoNT/A is the most potent protein toxin and causes fatal flaccid muscle paralysis by blocking neurotransmission. Application of BoNT/A has been extended to the fields of therapeutics and biodefense. Nevertheless, the global response of host immune cells to authentic BoNT/A has not been reported. Employing microarray analysis, we performed global transcriptional profiling of RAW264.7 cells, a murine alveolar macrophage cell line. We identified 70 genes that were modulated following 1 nM BoNT/A treatment. The altered genes were mainly involved in signal transduction, immunity and defense, protein metabolism and modification, neuronal activities, intracellular protein trafficking, and muscle contraction. Microarray data were validated with real-time RT-PCR for seven selected genes including tlr2, tnf, inos, ccl4, slpi, stx11, and irg1. Proinflammatory mediators such as nitric oxide (NO and tumor necrosis factor alpha (TNFα were induced in a dose-dependent manner in BoNT/A-stimulated RAW264.7 cells. Increased expression of these factors was inhibited by monoclonal anti-Toll-like receptor 2 (TLR2 and inhibitors specific to intracellular proteins such as c-Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK, and p38 mitogen-activated protein kinase (MAPK. BoNT/A also suppressed lipopolysaccharide-induced NO and TNFα production from RAW264.7 macrophages at the transcription level by blocking activation of JNK, ERK, and p38 MAPK. As confirmed by TLR2-/- knock out experiments, these results suggest that BoNT/A induces global gene expression changes in host immune cells and that host responses to BoNT/A proceed through a TLR2-dependent pathway, which is modulated by JNK, ERK, and p38 MAPK.

  17. Laser induced lifetime degradation in p-type crystalline silicon

    Pulsed, green laser irradiation of uncoated p-type silicon leads to a significant reduction of the effective minority carrier lifetime. The reason for the lifetime drop lies in the introduction of recombination centres into the laser melted and recrystallized surface layer, leading to a low local minority carrier lifetime τ ≈ 10 ns inside this surface layer. The laser treatment introduces the impurities oxygen, carbon and nitrogen into the silicon and further leads to an n-type doping of the surface layer. There are strong indications that these impurities are responsible for the observed n-type doping, as well as the lifetime reduction after irradiation. Both effects are removed by thermal annealing. An estimate shows that the low local lifetime does nevertheless not affect the performance of industrial or contacted selective solar cell emitter structures.

  18. The different neighbours around Type-1 and Type-2 active galactic nuclei

    Villarroel, Beatriz

    2014-01-01

    One of the most intriguing open issues in galaxy evolution is the structure and evolution of active galactic nuclei (AGN) that emit intense light believed to come from an accretion disk near a super-massive black hole (Rees 1984, Lynden-Bell 1969). To understand the zoo of different AGN classes, it has been suggested that all AGN are the same type of object viewed from different angles (Antonucci 1993). This model -- called AGN unification -- has been successful in predicting e.g. the existence of hidden broad optical lines in the spectrum of many narrow-line AGN. But this model is not unchallenged (Tran 2001) and it is an open problem whether more than viewing angle separates the so-called Type-1 and Type-2 AGN. Here we report the first large-scale study that finds strong differences in the galaxy neighbours to Type-1 and Type-2 AGN with data from the Sloan Digital Sky Survey (SDSS) (York et al. 2000) Data Release 7 (DR7) (Abazajian et al. 2008) and Galaxy Zoo (Lintott et al, 2008, Lintott et al 2011). We fi...

  19. Neutron induced activity in fuel element components

    A thorough investigation of the importance of various nuclides in neutron-induced radioactivity from fuel element construction materials has been carried out for both BWR and PWR fuel assemblies. The calculations were performed with the ORIGEN computer code. The investigation was directed towards the final storage of the assembly components and special emphasis was put to the examination of the sources of carbon-14, cobalt-60, nickel-59, nickel-63 and zirconium-93/niobium-93m. It is demonstrated that the nuclides nickel-59, in Inconel and stainless steel, and zirconium-93/niobium-93m, in Zircaloy, are the ones which constitute the very long term radiotoxic hazard of the irradiated materials. (author)

  20. Cell type-specific neuroprotective activity of untranslocated prion protein.

    Elena Restelli

    Full Text Available BACKGROUND: A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP. However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions. PRINCIPAL FINDINGS: Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells. SIGNIFICANCE: These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function.

  1. Activity trends in young solar-type stars

    Lehtinen, J.; Jetsu, L.; Hackman, T.; Kajatkari, P.; Henry, G. W.

    2016-04-01

    Aims: We study a sample of 21 young and active solar-type stars with spectral types ranging from late F to mid K and characterize the behaviour of their activity. Methods: We apply the continuous period search (CPS) time series analysis method on Johnson B- and V-band photometry of the sample stars, collected over a period of 16 to 27 years. Using the CPS method, we estimate the surface differential rotation and determine the existence and behaviour of active longitudes and activity cycles on the stars. We supplement the time series results by calculating new log R'HK = log F'HK/σTeff4 emission indices for the stars from high resolution spectroscopy. Results: The measurements of the photometric rotation period variations reveal a positive correlation between the relative differential rotation coefficient and the rotation period as k ∝ Prot1.36, but do not reveal any dependence of the differential rotation on the effective temperature of the stars. Secondary period searches reveal activity cycles in 18 of the stars and temporary or persistent active longitudes in 11 of them. The activity cycles fall into specific activity branches when examined in the log Prot/Pcyc vs. log Ro-1, where Ro-1 = 2Ωτc, or log Prot/Pcyc vs. log R'HK diagram. We find a new split into sub-branches within this diagram, indicating multiple simultaneously present cycle modes. Active longitudes appear to be present only on the more active stars. There is a sharp break at approximately log R'HK = -4.46 separating the less active stars with long-term axisymmetric spot distributions from the more active ones with non-axisymmetric configurations. In seven out of eleven of our stars with clearly detected long-term non-axisymmetric spot activity the estimated active longitude periods are significantly shorter than the mean photometric rotation periods. This systematic trend can be interpreted either as a sign of the active longitudes being sustained from a deeper level in the stellar interior

  2. Is type 1 diabetes a food-induced disease?

    Landin-Olsson, Mona; Hillman, Magnus; Erlanson-Albertsson, Charlotte

    2013-08-01

    The incidence of type 1 diabetes among children has almost doubled during the last decades in Sweden. Type 1 diabetes is considered as an autoimmune disease with unknown aetiology. Here we propose that the immune reaction may be initiated by food-derived mechanisms. The incidence of diabetes parallels an increased consumption of pasta, white bread, meat, cheese, low-fat milk, exotic fruits, soda, and snacks. Simultaneously, the consumption of potatoes, butter, high-fat milk, and domestic fruit has decreased. Three categories of food related reaction mechanisms are discussed against the following items (1) proteins from wheat, meat, and milk, (2) fat from processed food, and (3) exotic fruits. The current food consumption is suggested to initiate a pro-inflammatory reaction in the intestine and thereby reduce the intestinal barrier function. This may influence tolerance development and thus pave the way for an autoimmune attack on pancreatic beta cells. PMID:23688738

  3. E2 Proteins from High- and Low-Risk Human Papillomavirus Types Differ in Their Ability To Bind p53 and Induce Apoptotic Cell Death

    Parish, Joanna L; Kowalczyk, Anna; Chen, Hsin-Tien; Roeder, Geraldine E.; Sessions, Richard; Buckle, Malcolm; Gaston, Kevin

    2006-01-01

    The E2 proteins from oncogenic (high-risk) human papillomaviruses (HPVs) can induce apoptotic cell death in both HPV-transformed and non-HPV-transformed cells. Here we show that the E2 proteins from HPV type 6 (HPV6) and HPV11, two nononcogenic (low-risk) HPV types, fail to induce apoptosis. Unlike the high-risk HPV16 E2 protein, these low-risk E2 proteins fail to bind p53 and fail to induce p53-dependent transcription activation. Interestingly, neither the ability of p53 to activate transcri...

  4. Role of heat shock factor-1 activation in the doxorubicin-induced heart failure in mice

    Vedam, Kaushik; Nishijima, Yoshinori; Druhan, Lawrence J.; Khan, Mahmood; Moldovan, Nicanor I.; Zweier, Jay L.; Ilangovan, Govindasamy

    2010-01-01

    Treating cancer patients with chemotherapeutics, such as doxorubicin (Dox), cause dilated cardiomyopathy and congestive heart failure because of oxidative stress. On the other hand, heat shock factor-1 (HSF-1), a transcription factor for heat shock proteins (Hsps), is also known to be activated in response to oxidative stress. However, the possible role of HSF-1 activation and the resultant Hsp25 in chemotherapeutic-induced heart failure has not been investigated. Using HSF-1 wild-type (HSF-1...

  5. Dynamic changes of apoptosis in duck embryo fibroblasts induced by new type Gosling viral enteritis virus

    Shun Chen; Anchun Cheng; Mingshu Wang; Xiaoyue Chen

    2008-01-01

    The monolayer duck embryo fibroblast (DEF) cells were experimentally infected with new type Gosling viral enteritis virus (NGVEV) and the dynamic changes of apoptosis were detected at different time points after NGVEV infection by transmission electron microscopy (TEM), DNA agarose gel electrophoresis and Annexin V-FITC/PI stained fluorescence-activated cell sorter (FACS). The result shows that NGVEV can induce infected cells undergoing apoptosis and changing regularly. A series of characteristic apoptotic morphological changes including shrinkage of the cells, chromatin condensation and margination, as well as formation of apoptotic bodies, wereobserved by TEM. The typical ladder pattern of DNA fragmentation was demonstrated by agarose gel electrophoresis. And using flow cytometry analysis of Annexin V-FITC/PI staining, the dead, viable, apoptotic and necrotic cells could be analyzed quantitatively.

  6. Interconversion of Active and Inactive Conformations of Urokinase-Type Plasminogen Activator

    Liu, Zhuo; Kromann-Hansen, Tobias; Lund, Ida K;

    2012-01-01

    The catalytic activity of serine proteases depends on a salt-bridge between the amino group of residue 16 and the side chain of Asp194. The salt-bridge stabilizes the oxyanion hole and the S1 specificity pocket of the protease. Some serine proteases exist in only partially active forms, in which...... the amino group of residue 16 is exposed to the solvent. Such a partially active state is assumed by a truncated form of the murine urokinase-type plasminogen activator (muPA), consisting of residues 16-243. Here we investigated the allosteric interconversion between partially active states and the...

  7. Candesartan ameliorates impaired fear extinction induced by innate immune activation.

    Quiñones, María M; Maldonado, Lizette; Velazquez, Bethzaly; Porter, James T

    2016-02-01

    Patients with post-traumatic stress disorder (PTSD) tend to show signs of a relatively increased inflammatory state suggesting that activation of the immune system may contribute to the development of PTSD. In the present study, we tested whether activation of the innate immune system can disrupt acquisition or recall of auditory fear extinction using an animal model of PTSD. Male adolescent rats received auditory fear conditioning in context A. The next day, an intraperitoneal injection of lipopolysaccharide (LPS; 100 μg/kg) prior to auditory fear extinction in context B impaired acquisition and recall of extinction. LPS (100 μg/kg) given after extinction training did not impair extinction recall suggesting that LPS did not affect consolidation of extinction. In contrast to cued fear extinction, contextual fear extinction was not affected by prior injection of LPS (100 μg/kg). Although LPS also reduced locomotion, we could dissociate the effects of LPS on extinction and locomotion by using a lower dose of LPS (50 μg/kg) which impaired locomotion without affecting extinction. In addition, 15 h after an injection of 250 μg/kg LPS in adult rats, extinction learning and recall were impaired without affecting locomotion. A sub-chronic treatment with candesartan, an angiotensin II type 1 receptor blocker, prevented the LPS-induced impairment of extinction in adult rats. Our results demonstrate that activation of the innate immune system can disrupt auditory fear extinction in adolescent and adult animals. These findings also provide direction for clinical studies of novel treatments that modulate the innate immune system for stress-related disorders like PTSD. PMID:26520214

  8. L-type voltage-operated calcium channels contribute to astrocyte activation In vitro.

    Cheli, Veronica T; Santiago González, Diara A; Smith, Jessica; Spreuer, Vilma; Murphy, Geoffrey G; Paez, Pablo M

    2016-08-01

    We have found a significant upregulation of L-type voltage-operated Ca(++) channels (VOCCs) in reactive astrocytes. To test if VOCCs are centrally involved in triggering astrocyte reactivity, we used in vitro models of astrocyte activation in combination with pharmacological inhibitors, siRNAs and the Cre/lox system to reduce the activity of L-type VOCCs in primary cortical astrocytes. The endotoxin lipopolysaccharide (LPS) as well as high extracellular K(+) , glutamate, and ATP promote astrogliosis in vitro. L-type VOCC inhibitors drastically reduce the number of reactive cells, astrocyte hypertrophy, and cell proliferation after these treatments. Astrocytes transfected with siRNAs for the Cav1.2 subunit that conducts L-type Ca(++) currents as well as Cav1.2 knockout astrocytes showed reduce Ca(++) influx by ∼80% after plasma membrane depolarization. Importantly, Cav1.2 knock-down/out prevents astrocyte activation and proliferation induced by LPS. Similar results were found using the scratch wound assay. After injuring the astrocyte monolayer, cells extend processes toward the cell-free scratch region and subsequently migrate and populate the scratch. We found a significant increase in the activity of L-type VOCCs in reactive astrocytes located in the growing line in comparison to quiescent astrocytes situated away from the scratch. Moreover, the migration of astrocytes from the scratching line as well as the number of proliferating astrocytes was reduced in Cav1.2 knock-down/out cultures. In summary, our results suggest that Cav1.2 L-type VOCCs play a fundamental role in the induction and/or proliferation of reactive astrocytes, and indicate that the inhibition of these Ca(++) channels may be an effective way to prevent astrocyte activation. GLIA 2016. GLIA 2016;64:1396-1415. PMID:27247164

  9. Ultraviolet induced lysosome activity in corneal epithelium

    A 5.000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm-2 to 10.000 Jm-2 and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hsub(c) was 200 Jm-2 and lens threshold (Hsub(L)) was 7.500 Jm-2. The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared. (orig.)

  10. Angiotensin II type-2 receptor stimulation induces neuronal VEGF synthesis after cerebral ischemia.

    Mateos, Laura; Perez-Alvarez, Maria Jose; Wandosell, Francisco

    2016-07-01

    Intense efforts are being undertaken to understand the pathobiology of ischemia and to develop novel and effective treatments. Angiotensin II type 2 receptor (AT2R) is related with a beneficial role in neurodegenerative disorders, including ischemia. However, the underlying molecular mechanism remains elusive. In this study, we have established that AT2R stimulation by C21 compound, a specific AT2R agonist, caused a VEGF upregulation. Using mouse primary cortical neurons exposed to oxygen-glucose deprivation (OGD), we established that this effect was mediated by a mechanism dependent of mTORC1 signaling since mTOR inhibition abolished the C21-induced VEGF upregulation. Also, we have temporally characterized the changes on VEGF levels after ischemia induction in rats using two different approaches: transient and permanent middle cerebral artery occlusion (tMCAO and pMCAO). VEGF levels were permanently augmented after reperfusion (tMCAO) whereas lower levels of VEGF were found after pMCAO, remarkably at 21days. Therefore, C21 compound accelerated the recovery of the neurological status of pMCAO rats, reduced the ischemic damage area and abolished pMCAO-induced VEGF downregulation at 21days. This effect of C21 compound was mainly observed in neurons of the peri-infarct area. Our results suggest that a C21-induced VEGF upregulation may be crucial after an ischemic neuronal insult in both of our experimental approaches. This upregulation was mediated by a mechanism dependent of Akt/mTOR signaling pathway, since mTOR inhibition abolished the VEGF upregulation induced by C21. Considering that VEGF is involved in regenerative processes, we propose that AT2R activation could be used as a potential pharmacological strategy after ischemic stroke. PMID:27045356

  11. Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity

    Zhang, Li Li; Yan Liu, Dao; Ma, Li Qun;

    2007-01-01

    We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect...... of TRPV1 on cytosolic calcium was determined fluorometrically in 3T3-L1-preadipocytes and in human visceral fat tissue. Adipogenesis in stimulated 3T3-L1-preadipocytes was determined by oil red O-staining of intracellular lipid droplets, triglyceride levels, expression of peroxisome proliferator......-activated receptor-gamma, and expression of fatty acid synthase. Long-term feeding experiments were undertaken in wild-type mice and TRPV1 knockout mice. We detected TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans. In vitro, the TRPV1 agonist capsaicin dose-dependently induced...

  12. Localization of type I interferon receptor limits interferon-induced TLR-3 in epithelial cells

    This study aimed to expand on the role of type I IFNs in the influenza-induced upregulation of TLR3 and determine whether and how the localization of the IFN-alpha/beta receptor (IFNAR) in respiratory epithelial cells could modify IFN-induced responses. Using differentiated prima...

  13. An acidic sphingomyelinase Type C activity from Mycobacterium tuberculosis.

    Castro-Garza, Jorge; González-Salazar, Francisco; Quinn, Frederick D; Karls, Russell K; De La Garza-Salinas, Laura Hermila; Guzmán-de la Garza, Francisco J; Vargas-Villarreal, Javier

    2016-01-01

    Sphingomyelinases (SMases) catalyze the hydrolysis of sphingomyelin to ceramide and phosphorylcholine. Sphingolipids are recognized as diverse and dynamic regulators of a multitude of cellular processes mediating cell cycle control, differentiation, stress response, cell migration, adhesion, and apoptosis. Bacterial SMases are virulence factors for several species of pathogens. Whole cell extracts of Mycobacterium tuberculosis strains H37Rv and CDC1551 were assayed using [N-methyl-(14)C]-sphingomyelin as substrate. Acidic Zn(2+)-dependent SMase activity was identified in both strains. Peak SMase activity was observed at pH 5.5. Interestingly, overall SMase activity levels from CDC1551 extracts are approximately 1/3 of those of H37Rv. The presence of exogenous SMase produced by M. tuberculosis during infection may interfere with the normal host inflammatory response thus allowing the establishment of infection and disease development. This Type C activity is different from previously identified M. tuberculosis SMases. Defining the biochemical characteristics of M. tuberculosis SMases helps to elucidate the roles that these enzymes play during infection and disease. PMID:26948102

  14. The climatic change induced by human activities

    The climate of the Earth is a changing climate. Along their history many natural climate changes have existed in all time scales. At the present time we use the term climate changes have existed in all time scales. At the present time we use the term climate change in a restricted way, understanding that we have referring to a singular change that has their origin in the modification of the natural composition of the atmosphere. The increase of greenhouse gases from the second half the XVIII century, is due to the human activities of fossil fuels burning to obtain energy and to industrial and agricultural activities needing for the development of a world which population has been duplicated between 1960 and 2000, until overcoming the 6,000 million inhabitants. In particular, the concentrations of carbon dioxide-CO2 have increased in a 34%. The more recent emission scenarios proposed by the IPCC (SRES, 2000) are based on hypothesis about the population evolution, the energy consumption and the word patterns of development, which are grouped in four families dominated as A1, A2, B1 and B2. The answer for these scenarios from a range of climate models results in an increase of the world average surface atmospheric temperature between 1,4 degree centigrade and 5,8 degree centigrade and a corresponding sea level rise understood between 9 cm and 88 cm. The changes in the precipitation patterns show us that could be above to the current one in high and media latitudes and below in subtropical latitudes, with exceptions highly depending of the model used. (Author)

  15. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN

  16. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  17. Chimera-type states induced by local coupling

    Clerc, M. G.; Coulibaly, S.; Ferré, M. A.; García-Ñustes, M. A.; Rojas, R. G.

    2016-05-01

    Coupled oscillators can exhibit complex self-organization behavior such as phase turbulence, spatiotemporal intermittency, and chimera states. The latter corresponds to a coexistence of coherent and incoherent states apparently promoted by nonlocal or global coupling. Here we investigate the existence, stability properties, and bifurcation diagram of chimera-type states in a system with local coupling without different time scales. Based on a model of a chain of nonlinear oscillators coupled to adjacent neighbors, we identify the required attributes to observe these states: local coupling and bistability between a stationary and an oscillatory state close to a homoclinic bifurcation. The local coupling prevents the incoherent state from invading the coherent one, allowing concurrently the existence of a family of chimera states, which are organized by a homoclinic snaking bifurcation diagram.

  18. "EFFECT OF APAMIN ON TOLERANCE TO COCAINE-INDUCED LOCOMOTOR ACTIVITY IN MICE"

    H. R. Jamshidi; M. Rezayat M. R. Zarrindast

    2004-01-01

    In the present study, the effect of apamin (potassium channel blocker) on tolerance to cocaine-induced locomotor activity in mice has been investigated. Locomotor activity was measured by locomotor activity meter, Animax, type S (LKB, Farrad). Intraperitoneal (IP) injection of different doses of cocaine (2.5, 5, 10 and 15 mg/kg) produced dose-dependent locomotor activity in mice.Animals were treated with a dose of cocaine (60 mg/kg, IP) once daily, for 2, 3 or 4 days in order to produce toler...

  19. Mitochondrial apoptosis of lymphocyte is induced in type 2 diabetes

    Xu Hui; Chen Yanbo; Li Yanxiang; Xia Fangzhen; Han Bing; Zhang Huixin; Zhai Hualing

    2014-01-01

    Background Lymphocyte function and homeostasis is associated with immune defence to infection.Apoptosis of lymphocytes might be a considerably important component which has an impact on immunity to infections in people with hyperglycemia.The aim of this study was to explore the mitochondrial apoptosis pathway of lymphocyte in diabetic patients.Methods Sixty patients with type 2 diabetes mellitus and fifty healthy volunteers were included in this study.Annexin V and propidiumiodide (Pl) were joined in the isolated lymphocytes and the rate of lymphocyte apoptosis was calculated with flow cytometry.Observation of the lymphocytes was done using transmission electron microscopy; mitochondria had been extracted and then mitochondrial membrane potential (MMP) was detected to assess mitochondrial function; the mRNA level of Bcl-2,cytochrome c (Cyt-C),caspase-9 and caspase-3 were analyzed by real-time reverse transcriptionpolymerase chain reaction (RT-PCR).Results Apoptosis rate of lymphocyte was significantly higher in diabetic group than that in normal control group (P <0.05).Transmission electron microscopy showed lymphocyte shrinkage and breakage,chromatin condensation and less mitochondria; a fall in MMP levels was also evident; Bcl-2 concentration was reduced and the expressions of caspase-9,caspase-3 and Cyt-C were elevated (P <0.05) in diabetic patients.Conclusions The rate of lymphocyte apoptosis was significantly higher in type 2 diabetic patients than that in normal population.Mitochondrial apoptosis pathway may play a very important role in decreasing function of lymphocyte in diabetes.

  20. Nitric Oxide Synthase Type III Overexpression By Gene Therapy Exerts Antitumoral Activity In Mouse Hepatocellular Carcinoma

    Raúl González

    2015-08-01

    Full Text Available Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO synthase type III (NOS-3 overexpression induces cell death in hepatoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. Hepa 1-6 cells were used for in vitro and in vivo experiments. The first generation adenovirus was designed to overexpress NOS-3 (or GFP and luciferase cDNA under the regulation of murine alpha-fetoprotein (AFP and Rous Sarcoma Virus (RSV promoters, respectively. Both adenoviruses were administered through the tail vein two weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-Luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8 activity in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by l-NAME or p53 siRNA. The tail vein infusion of AFP-NOS- 3/RSV-Luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

  1. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells

  2. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    Kohio, Hinissan P.; Adamson, Amy L., E-mail: aladamso@uncg.edu

    2013-09-15

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells.

  3. VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

    Garcia-Roman, Jonathan; Ibarra-Sanchez, Alfredo; Lamas, Monica [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del IPN (Cinvestav, IPN) (Mexico); Gonzalez Espinosa, Claudia, E-mail: cgonzal@cinvestav.mx [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del IPN (Cinvestav, IPN) (Mexico)

    2010-10-15

    Research highlights: {yields} Bone marrow-derived mast cells (BMMCs) secrete functional VEGF but do not degranulate after Cobalt chloride-induced hypoxia. {yields} CoCl{sub 2}-induced VEGF secretion in mast cells occurs by a Ca{sup 2+}-insensitive but brefeldin A and Tetanus toxin-sensitive mechanism. {yields} Trolox and N-acetylcysteine inhibit hypoxia-induced VEGF secretion but only Trolox inhibits Fc{epsilon}RI-dependent anaphylactic degranulation in mast cells. {yields} Src family kinase Fyn activation after free radical production is necessary for hypoxia-induced VEGF secretion in mast cells. -- Abstract: Mast cells (MC) have an important role in pathologic conditions such as asthma and chronic obstructive pulmonary disease (COPD), where hypoxia conduce to deleterious inflammatory response. MC contribute to hypoxia-induced angiogenesis producing factors such as vascular endothelial growth factor (VEGF), but the mechanisms behind the control of hypoxia-induced VEGF secretion in this cell type is poorly understood. We used the hypoxia-mimicking agent cobalt chloride (CoCl{sub 2}) to analyze VEGF secretion in murine bone marrow-derived mast cells (BMMCs). We found that CoCl{sub 2} promotes a sustained production of functional VEGF, able to induce proliferation of endothelial cells in vitro. CoCl{sub 2}-induced VEGF secretion was independent of calcium rise but dependent on tetanus toxin-sensitive vesicle-associated membrane proteins (VAMPs). VEGF exocytosis required free radicals formation and the activation of Src family kinases. Interestingly, an important deficiency on CoCl{sub 2}-induced VEGF secretion was observed in Fyn kinase-deficient BMMCs. Moreover, Fyn kinase was activated by CoCl{sub 2} in WT cells and this activation was prevented by treatment with antioxidants such as Trolox and N-acetylcysteine. Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals

  4. VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

    Research highlights: → Bone marrow-derived mast cells (BMMCs) secrete functional VEGF but do not degranulate after Cobalt chloride-induced hypoxia. → CoCl2-induced VEGF secretion in mast cells occurs by a Ca2+-insensitive but brefeldin A and Tetanus toxin-sensitive mechanism. → Trolox and N-acetylcysteine inhibit hypoxia-induced VEGF secretion but only Trolox inhibits FcεRI-dependent anaphylactic degranulation in mast cells. → Src family kinase Fyn activation after free radical production is necessary for hypoxia-induced VEGF secretion in mast cells. -- Abstract: Mast cells (MC) have an important role in pathologic conditions such as asthma and chronic obstructive pulmonary disease (COPD), where hypoxia conduce to deleterious inflammatory response. MC contribute to hypoxia-induced angiogenesis producing factors such as vascular endothelial growth factor (VEGF), but the mechanisms behind the control of hypoxia-induced VEGF secretion in this cell type is poorly understood. We used the hypoxia-mimicking agent cobalt chloride (CoCl2) to analyze VEGF secretion in murine bone marrow-derived mast cells (BMMCs). We found that CoCl2 promotes a sustained production of functional VEGF, able to induce proliferation of endothelial cells in vitro. CoCl2-induced VEGF secretion was independent of calcium rise but dependent on tetanus toxin-sensitive vesicle-associated membrane proteins (VAMPs). VEGF exocytosis required free radicals formation and the activation of Src family kinases. Interestingly, an important deficiency on CoCl2-induced VEGF secretion was observed in Fyn kinase-deficient BMMCs. Moreover, Fyn kinase was activated by CoCl2 in WT cells and this activation was prevented by treatment with antioxidants such as Trolox and N-acetylcysteine. Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals-dependent Fyn kinase activation.

  5. Active Emergence from Propofol General Anesthesia Is Induced by Methylphenidate

    Chemali, Jessica J.; Van Dort, Christa J.; Brown, Emery N.; Solt, Ken

    2011-01-01

    Background: A recent study showed that methylphenidate induces emergence from isoflurane general anesthesia. Isoflurane and propofol are general anesthetics that may have distinct molecular mechanisms of action. The objective of this study was to test the hypothesis that methylphenidate actively induces emergence from propofol general anesthesia. Methods: Using adult rats, the effect of methylphenidate on time to emergence after a single bolus of propofol was determined. The ability of met...

  6. UV-induced DNA damage is an intermediate step in UV-induced expression of human immunodeficiency virus type 1, collagenase, c-fos, and metallothionein

    UV irradiation of human and murine cells enhances the transcription of several genes. Here we report on the primary target of relevant UV absorption, on pathways leading to gene activation, and on the elements receiving the UV-induced signal in the human immunodeficiency virus type 1 (HIV-1) long terminal repeat, in the gene coding for collagenase, and in the cellular oncogene fos. In order to induce the expression of genes, UV radiation needs to be absorbed by DNA and to cause DNA damage of the kind that cannot be repaired by cells from patients with xeroderma pigmentosum group A. UV-induced activation of the three genes is mediated by the major enhancer elements (located between nucleotide positions -105 and -79 of HIV-1, between positions -72 and -65 of the collagenase gene, and between positions -320 and -299 of fos). These elements share no apparent sequence motif and bind different trans-acting proteins; a member of the NF kappa B family binds to the HIV-1 enhancer, the heterodimer of Jun and Fos (AP-1) binds to the collagenase enhancer, and the serum response factors p67 and p62 bind to fos. DNA-binding activities of the factors recognizing the HIV-1 and collagenase enhancers are augmented in extracts from UV-treated cells. The increase in activity is due to posttranslational modification. While AP-1 resides in the nucleus and must be modulated there, NF kappa B is activated in the cytoplasm, indicating the existence of a cytoplasmic signal transduction pathway triggered by UV-induced DNA damage. In addition to activation, new synthesis of AP-1 is induced by UV radiation

  7. Music-induced emotions can be predicted from a combination of brain activity and acoustic features.

    Daly, Ian; Williams, Duncan; Hallowell, James; Hwang, Faustina; Kirke, Alexis; Malik, Asad; Weaver, James; Miranda, Eduardo; Nasuto, Slawomir J

    2015-12-01

    It is widely acknowledged that music can communicate and induce a wide range of emotions in the listener. However, music is a highly-complex audio signal composed of a wide range of complex time- and frequency-varying components. Additionally, music-induced emotions are known to differ greatly between listeners. Therefore, it is not immediately clear what emotions will be induced in a given individual by a piece of music. We attempt to predict the music-induced emotional response in a listener by measuring the activity in the listeners electroencephalogram (EEG). We combine these measures with acoustic descriptors of the music, an approach that allows us to consider music as a complex set of time-varying acoustic features, independently of any specific music theory. Regression models are found which allow us to predict the music-induced emotions of our participants with a correlation between the actual and predicted responses of up to r=0.234,pmusic induced emotions can be predicted by their neural activity and the properties of the music. Given the large amount of noise, non-stationarity, and non-linearity in both EEG and music, this is an encouraging result. Additionally, the combination of measures of brain activity and acoustic features describing the music played to our participants allows us to predict music-induced emotions with significantly higher accuracies than either feature type alone (p<0.01). PMID:26544602

  8. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr [Seoul National University Hospital, Biomedical Research Institute and Institute of Forensic Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Abdelmegeed, Mohamed A. [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States); Song, Byoung-Joon, E-mail: bj.song@nih.gov [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)

    2013-07-05

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI.

  9. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI

  10. Antiviral activity of four types of bioflavonoid against dengue virus type-2

    Zandi Keivan

    2011-12-01

    Full Text Available Abstract Background Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2 in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA and quantitative RT-PCR. Selectivity Index value (SI was determined as the ratio of cytotoxic concentration 50 (CC50 to inhibitory concentration 50 (IC50 for each compound. Results The half maximal inhibitory concentration (IC50 of quercetin against dengue virus was 35.7 μg mL-1 when it was used after virus adsorption to the cells. The IC50 decreased to 28.9 μg mL-1 when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL-1, respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC50 = 168.2 μg mL-1 and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC50 = 142.6 μg mL-1 when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL-1 reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. Conclusion Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other

  11. Treatment of Amiodarone-Induced Thyrotoxicosis Type 2 : A Randomized Clinical Trial

    Eskes, Silvia A.; Endert, Erik; Fliers, Eric; Geskus, Ronald B.; Dullaart, Robin P. F.; Links, Thera P.; Wiersinga, Wilmar M.

    2012-01-01

    Context: Amiodarone-induced thyrotoxicosis (AIT) type 2 is self-limiting in nature, but most physicians are reluctant to continue amiodarone. When prednisone fails to restore euthyroidism, possibly due to mixed cases of AIT type 1 and 2, perchlorate (ClO4) might be useful because ClO4 reduces the cy

  12. Propofol and magnesium attenuate isoflurane-induced caspase-3 activation via inhibiting mitochondrial permeability transition pore

    Zhang Yiying

    2012-08-01

    Full Text Available Abstract Background The inhalation anesthetic isoflurane has been shown to open the mitochondrial permeability transition pore (mPTP and induce caspase activation and apoptosis, which may lead to learning and memory impairment. Cyclosporine A, a blocker of mPTP opening might attenuate the isoflurane-induced mPTP opening, lessening its ripple effects. Magnesium and anesthetic propofol are also mPTP blockers. We therefore set out to determine whether propofol and magnesium can attenuate the isoflurane-induced caspase activation and mPTP opening. Methods We investigated the effects of magnesium sulfate (Mg2+, propofol, and isoflurane on the opening of mPTP and caspase activation in H4 human neuroglioma cells stably transfected to express full-length human amyloid precursor protein (APP (H4 APP cells and in six day-old wild-type mice, employing Western blot analysis and flowcytometry. Results Here we show that Mg2+ and propofol attenuated the isoflurane-induced caspase-3 activation in H4-APP cells and mouse brain tissue. Moreover, Mg2+ and propofol, the blockers of mPTP opening, mitigated the isoflurane-induced mPTP opening in the H4-APP cells. Conclusion These data illustrate that Mg2+ and propofol may ameliorate the isoflurane-induced neurotoxicity by inhibiting its mitochondrial dysfunction. Pending further studies, these findings may suggest the use of Mg2+ and propofol in preventing and treating anesthesia neurotoxicity.

  13. Dimer formation of receptor activator of nuclear factor κB induces incomplete osteoclast formation

    Receptor activator of nuclear factor κB-ligand (RANKL) transduces a differentiation signal appropriate to osteoclasts likely through induction a receptor homotrimer; however, biological importance of RANK-trimerizarion is unknown. To address the signaling mechanism of the RANK receptor, we analyzed the effect of two different types of homodimer inducers RANK-TM-FKBP36v and hEpoR-RANK-TM on osteoclastogenesis. Dimerizing component FKBP36v or extracellular portion of human erythropoietin receptor (hEpoR) was fused to RANK lacking the extracellular domain, and the dimerization of this fusion protein was induced by addition of the chemical inducer of dimerization AP20187 or erythropoietin, respectively. Such treatment resulted in induction of TRAP-activity, a marker of osteoclast in a dose dependent manner, with an efficiency equivalent to that of induction by RANKL. However, dimerized-RANK-induced osteoclasts showed relatively low levels of multinucleation, pit forming activity, and expression of calcitonin receptor and cathepsin K, compared with osteoclasts which were induced in the presence of RANKL. As expression of nuclear factor of activated T cells 1 (NFATc1) was also reduced in dimerized-RANK-induced osteoclasts, RANK oligomerization by RANKL is a critical event to generate fully matured osteoclasts through upregulation of NFATc1

  14. Methods to distinguish various types of protein phosphatase activity

    To distinguish the action of protein Tyr(P) and protein Ser(P)/Thr(P) phosphatases on 32P-labeled phosphoproteins in subcellular fractions different inhibitors and activators are utilized. Comparison of the effects of added compounds provides a convenient, indirect method to characterize dephosphorylation reactions. Protein Tyr(P) phosphatases are specifically inhibited by micromolar Zn2+ or vanadate, and show maximal activity in the presence of EDTA. The other class of cellular phosphatases, specific for protein Ser(P) and Thr(P) residues, are inhibited by fluoride and EDTA. In this class of enzymes two major functional types can be distinguished: those sensitive to inhibition by the heat-stable protein inhibitor-2 and not stimulated by polycations, and those not sensitive to inhibition and stimulated by polycations. Preparation of 32P-labeled Tyr(P) and Ser(P) phosphoproteins also is presented for the direct measurement of phosphatase activities in preparations by the release of acid-soluble [32P]phosphate

  15. Fluoxetine-induced transactivation of the platelet-derived growth factor type β receptor reveals a novel heterologous desensitization process.

    Kruk, Jeff S; Vasefi, Maryam S; Gondora, Nyasha; Ahmed, Nawaz; Heikkila, John J; Beazely, Michael A

    2015-03-01

    Many G protein-coupled receptors (GPCRs), including serotonin (5-HT) receptors promote the activity of receptor tyrosine kinases (RTKs) via intracellular signaling pathways in a process termed transactivation. Although transactivation pathways are commonly initiated by a GPCR, a recent report demonstrated that serotonin-selective reuptake inhibitors (SSRIs) were able to block 5-HT-induced transactivation of the platelet-derived growth factor (PDGF) type β receptor. We show that a 45 min pretreatment of SH-SY5Y cells with the SSRI fluoxetine indeed blocked 5-HT-induced transactivation of the PDGFβ receptor. However, upon further examination, we discovered that during the pretreatment period, fluoxetine itself was transiently transactivating the PDGFβ receptor via 5-HT2 receptor activation. After 45min, the increase in PDGFβ receptor phosphorylation induced by fluoxetine had returned to baseline, but a subsequent transactivating stimulus (5-HT) failed to "re-transactivate" the PDGFβ receptor. We further demonstrate that 45min, but not 3h, 5-HT pretreatment blocks dopamine-induced PDGFβ receptor transactivation. This did not involve changes in PDGF receptor function, since ligand (PDGF)-induced PDGFβ receptor activation was not inhibited by 5-HT pretreatment. To our knowledge this is the first demonstration of the heterologous desensitization of an RTK transactivation pathway and reveals a previously unknown short-term "blackout" period where no additional transactivation signaling is possible. PMID:25702926

  16. Proteases induce secretion of collagenase and plasminogen activator by fibroblasts

    Werb, Z.; Aggeler, J.

    1978-04-01

    We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2 to 24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or ..cap alpha..-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16 to 48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10/sup 6/ cells per 24 hr) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continued presence of proteolytic activity or on subsequent cell adhesion, spreading, or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, ..cap alpha../sub 1/-antitrypsin, bovine serum albumin, collagen, and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.

  17. Plasmodium chabaudi limits early Nippostrongylus brasiliensis-induced pulmonary immune activation and Th2 polarization in co-infected mice

    Hoeve, Marieke A.; Mylonas, Katie J; Fairlie-Clarke, Karen J; Mahajan, Simmi M; Allen, Judith E.; Graham, Andrea L

    2009-01-01

    Larvae of several common species of parasitic nematodes obligately migrate through, and often damage, host lungs. The larvae induce strong pulmonary Type 2 immune responses, including T-helper (Th)2 cells as well as alternatively activated macrophages (AAMphi) and associated chitinase and Fizz/resistin family members (ChaFFs), which are thought to promote tissue repair processes. Given the prevalence of systemic or lung-resident Type 1-inducing pathogens in geographical areas in which nematod...

  18. Residual activity induced by ion bombardment on insulating samples

    In this work we investigate some properties of the residual activity induced by protons impinging on quartz, mylar and other insulating materials. In particular, we discuss the time constant related to the decay of the emitted radiation after the primary ion beam is turned off. This radiation includes a continuum of bremsstrahlung and, in some cases, characteristic X-rays induced in the process as well. In general, the results indicate the presence of two time constants in the decaying process. Moreover, it appears that the residual activity has a strong dependence on the material specifications and on the conditions of the surface under bombardment. A simple mechanism for this process is suggested

  19. Base substitution mutations induced by metabolically activated aflatoxin B1.

    Foster, P L; Eisenstadt, E; Miller, J H

    1983-05-01

    We have determined the base substitutions generated by metabolically activated aflatoxin B1 in the lacI gene of a uvrB- strain of Escherichia coli. By monitoring over 70 different nonsense mutation sites, we show that activated aflatoxin B1 specifically induced GxC leads to TxA transversions. One possible pathway leading to this base change involves depurination at guanine residues. We consider this mechanism of mutagenesis in the light of our other findings that the carcinogens benzo[a]pyrene diol epoxide and N-acetoxyacetylaminofluorene also specifically induce GxC leads to TxA transversions. PMID:6405385

  20. Bicyclic Peptide Inhibitor of Urokinase-Type Plasminogen Activator

    Roodbeen, Renée; Paaske, Berit; Jiang, Longguang;

    2013-01-01

    The development of protease inhibitors for pharmacological intervention has taken a new turn with the use of peptidebased inhibitors. Here, we report the rational design of bicyclic peptide inhibitors of the serine protease urokinase-type plasminogen activator (uPA), based on the established...... monocyclic peptide, upain-2. It was successfully converted to a bicyclic peptide, without loss of inhibitory properties. The aim was to produce a peptide cyclised by an amide bond with an additional stabilising across-the-ring covalent bond. We expected this bicyclic peptide to exhibit a lower entropic...... burden upon binding. Two bicyclic peptides were synthesised with affinities similar to that of upain-2, and their binding energetics were evaluated by isothermal titration calorimetry. Indeed, compared to upain-2, the bicyclic peptides showed reduced loss of entropy upon binding to uPA. We also...

  1. Zeeman-Doppler imaging of active young solar type stars

    Hackman, Thomas; Rosén, Lisa; Kochukhov, Oleg; Käpylä, Maarit J

    2015-01-01

    By studying young magnetically active late-type stars, i.e. analogues to the young Sun, one can draw conclusions on the evolution of the solar dynamo. We determine the topology of the surface magnetic field and study the relation between the magnetic field and cool photospheric spots in three young late-type stars. High-resolution spectropolarimetry of the targets were obtained with the HARPSpol instrument mounted at the ESO 3.6 m telescope. The signal-to-noise ratio of the Stokes IV measurements were boosted by combining the signal from a large number of spectroscopic absorption lines through the least squares deconvolution technique. Surface brightness and magnetic field maps were calculated using the Zeeman-Doppler imaging technique. All the three targets show clear signs of both magnetic fields and cool spots. Only one of the targets, namely V1358 Ori, shows evidence of the dominance of non-axisymmetric modes. In two of the targets, the poloidal field is significantly stronger than the toroidal one, indic...

  2. Antidiabetic activity of Rheum emodi in Alloxan induced diabetic rats.

    Radhika.R

    2010-09-01

    Full Text Available The present study was carried out to evaluate the antidiabetic effect of Rheum emodi rhizome extract and to study the activities of hexokinase, aldolase and phosphoglucoisomerase, and gluconeogenic enzymes such as glucose-6- phosphatase and fructose 1,6-diphosphatase in liver and kidney of normal and alloxan induced diabetic rats. Oral administration of 75 % ethanolic extract of R. emodi (250 mg/kg body weight for 30 days, resulted in decrease inthe activities of glucose-6-phosphatase, fructose-1,6-disphosphatase, aldolase and an increase in the activity of phosphoglucoisomerase and hexokinase in tissues. The study clearly shows that the R.emodi possesses antidiabetic activity.

  3. Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities

    Chi-Ming Lee

    2013-01-01

    Full Text Available Rutaecarpine (RUT, the major bioactive ingredient isolated from the Chinese herb Evodia rutaecarpa, possesses a wide spectrum of biological activities, including anti-inflammation and preventing cardiovascular diseases. However, its high cytotoxicity hampers pharmaceutical development. We designed and synthesized a derivative of RUT, bromo-dimethoxyrutaecarpine (Br-RUT, which showed no cytotoxicity at 20 μM. Br-RUT suppressed nitric oxide (NO production and tumor necrosis factor-α release in concentration-dependent (0~20 μM manners in lipopolysaccharide (LPS-treated RAW 264.7 macrophages; protein levels of inducible NO synthase (iNOS and cyclooxygenase-2 induced by LPS were downregulated. Br-RUT inhibited cell migration and invasion of ovarian carcinoma A2780 cells with 0~48 h of treatment. Furthermore, Br-RUT enhanced the expression of transient receptor potential vanilloid type 1 and activated endothelial NOS in human aortic endothelial cells. These results suggest that the synthetic Br-RUT possesses very low cytotoxicity but retains its activities against inflammation and vasodilation that could be beneficial for cardiovascular disease therapeutics.

  4. Child physical activity and parent-child attitude congruence of athletic competence and activity type

    Our purpose was to evaluate parental influence on child physical activity (PA) through parental beliefs on child competence and importance of specific types of PA. Utilizing Eccles' expectancy-value model of task choice, the study examined parent-child attitude congruence and whether task value bel...

  5. Porcine Circovirus Type 2 Activates CaMMKβ to Initiate Autophagy in PK-15 Cells by Increasing Cytosolic Calcium

    Yuanxing Gu; Baozhu Qi; Yingshan Zhou; Xiaowu Jiang; Xian Zhang; Xiaoliang Li; Weihuan Fang

    2016-01-01

    Porcine circovirus type 2 (PCV2) induces autophagy via the 5′ adenosine monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) pathway in pig kidney PK-15 cells. However, the underlying mechanisms of AMPK activation in autophagy induction remain unknown. With specific inhibitors and RNA interference (RNAi), we show that PCV2 infection upregulated calcium/calmodulin-dependent protein kin...

  6. Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord

    Kaufmann, Nathalie; Zeka, Bleranda; Schanda, Kathrin; Fujihara, Kazuo; Illes, Zsolt; Dahle, Charlotte; Reindl, Markus; Lassmann, Hans; Bradl, Monika

    2016-01-01

    Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN. PMID:26990978

  7. Celiac anti-type 2 transglutaminase antibodies induce phosphoproteome modification in intestinal epithelial Caco-2 cells.

    Gaetana Paolella

    Full Text Available BACKGROUND: Celiac disease is an inflammatory condition of the small intestine that affects genetically predisposed individuals after dietary wheat gliadin ingestion. Type 2-transglutaminase (TG2 activity seems to be responsible for a strong autoimmune response in celiac disease, TG2 being the main autoantigen. Several studies support the concept that celiac anti-TG2 antibodies may contribute to disease pathogenesis. Our recent findings on the ability of anti-TG2 antibodies to induce a rapid intracellular mobilization of calcium ions, as well as extracellular signal-regulated kinase phosphorylation, suggest that they potentially act as signaling molecules. In line with this concept, we have investigated whether anti-TG2 antibodies can induce phosphoproteome modification in an intestinal epithelial cell line. METHODS AND PRINCIPAL FINDINGS: We studied phosphoproteome modification in Caco-2 cells treated with recombinant celiac anti-TG2 antibodies. We performed a two-dimensional electrophoresis followed by specific staining of phosphoproteins and mass spectrometry analysis of differentially phosphorylated proteins. Of 14 identified proteins (excluding two uncharacterized proteins, three were hypophosphorylated and nine were hyperphosphorylated. Bioinformatics analyses confirmed the presence of phosphorylation sites in all the identified proteins and highlighted their involvement in several fundamental biological processes, such as cell cycle progression, cell stress response, cytoskeletal organization and apoptosis. CONCLUSIONS: Identification of differentially phosphorylated proteins downstream of TG2-antibody stimulation suggests that in Caco-2 cells these antibodies perturb cell homeostasis by behaving as signaling molecules. We hypothesize that anti-TG2 autoantibodies may destabilize the integrity of the intestinal mucosa in celiac individuals, thus contributing to celiac disease establishment and progression. Since several proteins here

  8. Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis

    Stav Sapoznik

    2016-02-01

    Full Text Available In recent years, the notion that ovarian carcinoma results from ovulation-induced inflammation of the fallopian tube epithelial cells (FTECs has gained evidence. However, the mechanistic pathway for this process has not been revealed yet. In the current study, we propose the mutator protein activation-induced cytidine deaminase (AID as a link between ovulation-induced inflammation in FTECs and genotoxic damage leading to ovarian carcinogenesis. We show that AID, previously shown to be functional only in B lymphocytes, is expressed in FTECs under physiological conditions, and is induced in vitro upon ovulatory-like stimulation and in vivo in carcinoma-associated FTECs. We also report that AID activity results in epigenetic, genetic and genomic damage in FTECs. Overall, our data provides new insights into the etiology of ovarian carcinogenesis and may set the ground for innovative approaches aimed at prevention and early detection.

  9. Induced Dwarf Mutant in Catharanthus roseus with Enhanced Antibacterial Activity

    Verma, A.K.; Singh, R R

    2010-01-01

    Evaluation of an ethyl methane sulphonate-induced dwarf mutant of Catharanthus roseus (L.) G. Don revealed that the mutant exhibited marked variation in morphometric parameters. The in vitro antibacterial activity of the aqueous and alcoholic leaf extracts of the mutant and control plants was investigated against medically important bacteria. The mutant leaf extracts showed enhanced antibacterial activity against all the tested bacteria except Bacillus subtilis.

  10. Induced dwarf mutant in Catharanthus roseus with enhanced antibacterial activity

    Verma A

    2010-01-01

    Full Text Available Evaluation of an ethyl methane sulphonate-induced dwarf mutant of Catharanthus roseus (L. G. Don revealed that the mutant exhibited marked variation in morphometric parameters. The in vitro antibacterial activity of the aqueous and alcoholic leaf extracts of the mutant and control plants was investigated against medically important bacteria. The mutant leaf extracts showed enhanced antibacterial activity against all the tested bacteria except Bacillus subtilis.