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Sample records for factor kappab activation

  1. Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis

    DEFF Research Database (Denmark)

    Jørgensen, V.L.; Perner, A.; Hansen, A.

    2005-01-01

    Expression of inducible nitric oxide synthase (iNOS) is greatly upregulated in the colonic mucosa of patients with collagenous and ulcerative colitis. As the transcription factor nuclear factor kappaB (NFkappaB) is a major inducer of iNOS gene expression, we compared activation and transcriptional...

  2. Cardiovascular disease associated with radiotherapy: activation of nuclear factor kappa-B.

    Science.gov (United States)

    Halle, M; Hall, P; Tornvall, P

    2011-05-01

    There have been several recent reports of an increased risk of cardiovascular disease after radiotherapy. Hence, with an increasing number of cancer survivors, the incidence of cardiovascular disease caused by radiotherapy will increase. The existence of a type of vascular disease, or vasculopathy, induced by radiotherapy has been known for decades. It is important to identify and understand the molecular causes of this vasculopathy to determine preventive strategies. Recently, a chronic inflammation with similarities to atherosclerosis has been observed, with activation of the transcription factor nuclear factor kappa-B (NF-κB) as a possible cause. However, the trigger for NF-κB activation is unclear although it may be that reactive oxygen species or direct DNA damage is involved. To minimize the risk of cardiovascular disease in vulnerable patients, careful selection of patients, radiation dose and fractionation are important, together with the development of new techniques that reduce radiation dose to the blood vessels. In the light of the finding of an interaction between risk factors for cardiovascular disease and radiotherapy, it is reasonable to modify these factors including diabetes mellitus, hyperlipidaemia, hypertension and smoking. We believe that preventive strategies focusing on NF-κB can reduce the risk of future adverse cardiovascular events. © 2011 The Association for the Publication of the Journal of Internal Medicine.

  3. Ghrelin inhibits the development of acute pancreatitis and nuclear factor kappaB activation in pancreas and liver.

    Science.gov (United States)

    Zhou, Xiaolei; Xue, Chengrui

    2009-10-01

    To investigate the influence of ghrelin on the development of severe acute pancreatitis (SAP) and the expression of nuclear factor kappaB (NF-kappaB) p65 in the pancreas and liver. Severe acute pancreatitis was induced in rat by sodium taurocholate injection in the pancreaticobiliary duct. Ghrelin was administrated twice at the dose 10 or 20 nmol/kg per injection, respectively. Then, serum amylase activity; serum tumor necrosis factor alpha, interleukin 1beta, and interleukin 6 concentrations; and morphological signs of pancreatitis and hepatic damage were measured. Meanwhile, determination of pancreatic and hepatic NF-kappaB p65 expression was performed by Western blotting and immunohistochemistry. The serumal parameters increased, and morphological damages were observed in the pancreas and liver in SAP rats. Nuclear factor kappaB p65 expression was significantly higher in the pancreas and liver than sham-operated rats (P pancreas and liver. Ghrelin inhibits the development of acute pancreatitis induced by sodium taurocholate. It exerts the therapeutic effects through inhibiting NF-kappaB expression, thereby blocks the inflammatory signal transduction pathway and reduces the release of inflammatory media and cytokines.

  4. Real-time monitoring of nuclear factor kappaB activity in cultured cells and in animal models.

    Science.gov (United States)

    Badr, Christian E; Niers, Johanna M; Tjon-Kon-Fat, Lee-Ann; Noske, David P; Wurdinger, Thomas; Tannous, Bakhos A

    2009-01-01

    Nuclear factor kappaB (NF-kappaB) is a transcription factor that plays a major role in many human disorders, including immune diseases and cancer. We designed a reporter system based on NF-kappaB responsive promoter elements driving expression of the secreted Gaussia princeps luciferase (Gluc). We show that this bioluminescent reporter is a highly sensitive tool for noninvasive monitoring of the kinetics of NF-kappaB activation and inhibition over time, both in conditioned medium of cultured cells and in the blood and urine of animals. NF-kappaB activation was successfully monitored in real time in endothelial cells in response to tumor angiogenic signaling, as well as in monocytes in response to inflammation. Further, we demonstrated dual blood monitoring of both NF-kappaB activation during tumor development as correlated to tumor formation using the NF-kappaB Gluc reporter, as well as the secreted alkaline phosphatase reporter. This NF-kappaB reporter system provides a powerful tool for monitoring NF-kappaB activity in real time in vitro and in vivo.

  5. Physiologic activation of nuclear factor kappa-B in the endometrium during the menstrual cycle is altered in endometriosis patients.

    Science.gov (United States)

    González-Ramos, Reinaldo; Rocco, Jocelyn; Rojas, Candy; Sovino, Hugo; Poch, Andrea; Kohen, Paulina; Alvarado-Díaz, Carlos; Devoto, Luigi

    2012-03-01

    To evaluate nuclear factor kappaB (NF-κB) activation and NF-κB-p65 subunit activation, immunolocalization, and expression in the endometrium of healthy women and endometriosis patients throughout the menstrual cycle. Prospective observational study. Affiliated hospital and university research laboratory. Twenty-four healthy women and 24 endometriosis patients. Menstrual, proliferative, and secretory endometrial biopsies. Assessment of NF-κB and p65 activation by protein-DNA binding assays and p65 localization and expression by immunohistochemistry. Total NF-κB-DNA binding was constitutive and variable in human endometrium accross the menstrual cycle. Healthy women (physiologic conditions) showed higher p65-DNA binding in proliferative than in menstrual and secretory endometrium. Conversely, in endometriosis patients, p65-DNA binding was higher in proliferative and secretory endometrium than in menstrual endometrium. Endometrial epithelial cells showed higher p65 expression level score than endometrial stromal cells. NF-κB activity is constitutive, physiologic, and variable in human endometrium. The physiologic cyclic p65 activation pattern was altered in endometriosis patients, showing no cyclic variation between the proliferative and secretory phase of the menstrual cycle. The absence of decreased p65 activity in secretory endometrium from endometriosis patients is concurrent with progesterone resistance and could participate in endometrial biologic alterations during the implantation window in endometriosis patients. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Effect of resveratrol on activation of nuclear factor kappa-B and inflammatory factors in rat model of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yong Meng; Qing-Yong Ma; Xiao-Ping Kou; Jun Xu

    2005-01-01

    AIM: To observe the effect of resveratrol on nuclear factor Kappa-B (NF-κB) activation and the inflammatory response in sodium taurocholate-induced pancreatitis in rats.METHODS: Seventy-two male SD rats were randomly divided into three groups: sham operation group (control),severe acute pancreatitis (SAP) group, and severe acute pancreatitis group treated with resveratrol (RES). A SAP model was established by injecting 4% sodium taurocholate 1 mL/kg through puncturing the pancreatic duct. In Res group, Res was given at 30 mg/kg b.m. intraperitoneally after the SAP model was successfully established. Eight animals from each group were sacrificed at 3, 6 and 12 h after modeling. The expression of NF-κB activation of pancreas was detected by immunohistochemical staining, whereas the levels of TNF-α and IL-8 in pancreatic tissues were estimated by radioimmunoassay. The pathological changes of pancreas and lungs were examined microscopically.RESULTS: Much less hyperemia, edema, dust-colored necrotic focus and soaps were noticed in pancreas in RES group than in SAP group. In RES group, hemorrhage,exudates and infiltration of inflammatory cells in pancreas and interstitial edema, destruction of alveolar wall in lung were significantly less than in SAP group. In the SAP group,the activation of NF-κB in pancreatic tissues was enhanced significantly at any measure point compared with control group (64.23±10.72% vs2.56±0.65%, 55.86±11.34% vs 2.32±0.42%, 36.23±2.30% vs 2.40±0.36% ,P <0.01), TNF-α,IL-8 were also increased and reached their peak at 6 h and then declined. The activation of NF-κB and the levels of TNF-α and IL-8 in RES group were significantly lower than those in SAP group (P<0.01): activation (52.63±9.45% vs 64.23±10.72%, 40.52±8.40% vs 55.86±11.34%, 29.83±5.37% vs36.23±2.30%), TN-α (132.76±15.68 pg/mL vs 158.36±12.58 pg/mL, 220.32±23.57 pg/mL vs 247.67± 11.62 pg/mL, 175.68±18.43 pg/mL vs 197.35±12.57 pg/mL) and IL-8 (0.62±0.21

  7. Prognostic value of receptor activator of nuclear factor kappa-B (RANK marker in patients with breast cancer

    Directory of Open Access Journals (Sweden)

    S. I. Zabroda

    2015-01-01

    Full Text Available Despite notable progress made in studying breast cancer (BC, the mechanisms of metastases, in view of the classification into molecular subtypes, in patients with BC remain to be fully uninvestigated, in the presence of a good prognosis in particular. To study novel diagnostic and predictive markers in a new way presents current problems in the pathology of BC. This investigation deals with the expression of osteoprotegerin (OPG in the tumor cells of patients with BC. It enrolled 83 patients with locally advanced BC (T2–4N0–3M0 who had been treated in 2003 to 2010. The inclusion criterion was a histologically verified diagnosis of invasive BC. To study the level of OPG, the investigators conducted an immunohistochemical study of biopsy sections according to the standard protocol. The mean expression of receptor activator of nuclear factor kappa-B (RANK in the BC cells was 18.7 %; itsmedian was 5 % (range, 0–90 %. The patients were divided into 2 groups according to the level of RANK expression: 1 high (higher than the median; 2 low (lower than the median. The high RANK group included 39 patients; the low RANK group comprised 44 patients. Analysis of the clinical and pathological characteristics of BC patients with regard RANK expression did not show any statistically significant differences in the presence or absence of affected regional lymph nodes, T category, and Ki-67 index. The analysis of clinical and pathomorphological and immunohistochemical characteristics in patients with breast cancer, taking into consideration RANK expression level, did not show any statistically significant differences with respect to presence or absence of affected regional lymph nodes, age, T category and Ki-67 index (р > 0.05. However, it revealed the following pattern: the high expression of RANK was more common in patients positive for estrogen and progesterone receptors than in those for negative receptors (p = 0.04.

  8. Phytochemicals of Aristolochia tagala and Curcuma caesia exert anticancer effect by tumor necrosis factor-α-mediated decrease in nuclear factor kappaB binding activity

    Science.gov (United States)

    Hadem, Khetbadei Lysinia Hynniewta; Sharan, Rajeshwar Nath; Kma, Lakhan

    2015-01-01

    Rationale: The active compounds or metabolites of herbal plants exert a definite physiological action on the human body and thus are widely used in human therapy for various diseases including cancer. Previous studies by our group have reported the anticarcinogenic properties of the two herbal plants extracts (HPE) of Aristolochia tagala (AT) Cham. and Curcuma caesia (CC) Roxb. in diethylnitrosamine-induced mouse liver cancer in vivo. The anticarcinogenic properties of these extracts may be due to the active compounds present in them. Objectives: Our objective was to analyze the phytochemical constituents present in AT and CC, to assay their antioxidant properties and to determine their role in a possible intervention on tumor progression. Materials and Methods: Qualitative and quantitative analysis of constituent with anticancer properties present in the crude methanol extract of the two plants CC and AT was carried out following standard methods. Separation of the phytochemical compounds was done by open column chromatography. The extracts were eluted out with gradients of chloroform-methanol solvents. Ultraviolet-visible spectra of individual fractions were recorded, and the fractions were combined based on their λmax. The free radical scavenging activity of crude extracts and fractions obtained was also determined; the radical scavenging activity was expressed as IC50. High-performance thin layer chromatography (HPTLC) analysis of fractionated compounds was carried out to identify partially the phytochemical compounds. The anti-inflammatory and anticancer activity of AT and CC extracts was studied in DEN induced BALB/c mice by analyzing the tumor necrosis factor-α (TNF-α) levels in serum and the nuclear factor kappaB (NF-κB) binding activity in nuclear extracts of the liver. Results: It was observed that both AT and CC contained compounds such as phenolics, tannins, flavonoids, terpenoids, etc., and both extracts exhibited antioxidant capacity. HPTLC

  9. Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization

    NARCIS (Netherlands)

    Kuznetsova, T.; Wang, S.Y.; Rao, N.A.; Mandoli, A.; Martens, J.H.; Rother, N; Aartse, A.; Groh, L.; Janssen-Megens, E.M.; Li, G.; Ruan, Y.; Logie, C.; Stunnenberg, H.G.

    2015-01-01

    BACKGROUND: The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activ

  10. Cocaine induces cell death and activates the transcription nuclear factor kappa-b in pc12 cells

    Science.gov (United States)

    Lepsch, Lucilia B; Munhoz, Carolina D; Kawamoto, Elisa M; Yshii, Lidia M; Lima, Larissa S; Curi-Boaventura, Maria F; Salgado, Thais ML; Curi, Rui; Planeta, Cleopatra S; Scavone, Cristoforo

    2009-01-01

    Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several neurotransmitter systems. For example, cocaine increases extracellular levels of dopamine and free radicals, and modulates several transcription factors. NF-κB is a transcription factor that regulates gene expression involved in cellular death. Our aim was to investigate the toxicity and modulation of NF-κB activity by cocaine in PC 12 cells. Treatment with cocaine (1 mM) for 24 hours induced DNA fragmentation, cellular membrane rupture and reduction of mitochondrial activity. A decrease in Bcl-2 protein and mRNA levels, and an increase in caspase 3 activity and cleavage were also observed. In addition, cocaine (after 6 hours treatment) activated the p50/p65 subunit of NF-κB complex and the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, attenuated the NF-κB activation. Inhibition of NF-κB activity by using PDTC and Sodium Salicilate increased cell death caused by cocaine. These results suggest that cocaine induces cell death (apoptosis and necrosis) and activates NF-κB in PC12 cells. This activation occurs, at least partially, due to activation of D1 receptors and seems to have an anti-apoptotic effect on these cells. PMID:19183502

  11. Cocaine induces cell death and activates the transcription nuclear factor kappa-b in pc12 cells

    Directory of Open Access Journals (Sweden)

    Lepsch Lucilia B

    2009-02-01

    Full Text Available Abstract Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several neurotransmitter systems. For example, cocaine increases extracellular levels of dopamine and free radicals, and modulates several transcription factors. NF-κB is a transcription factor that regulates gene expression involved in cellular death. Our aim was to investigate the toxicity and modulation of NF-κB activity by cocaine in PC 12 cells. Treatment with cocaine (1 mM for 24 hours induced DNA fragmentation, cellular membrane rupture and reduction of mitochondrial activity. A decrease in Bcl-2 protein and mRNA levels, and an increase in caspase 3 activity and cleavage were also observed. In addition, cocaine (after 6 hours treatment activated the p50/p65 subunit of NF-κB complex and the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, attenuated the NF-κB activation. Inhibition of NF-κB activity by using PDTC and Sodium Salicilate increased cell death caused by cocaine. These results suggest that cocaine induces cell death (apoptosis and necrosis and activates NF-κB in PC12 cells. This activation occurs, at least partially, due to activation of D1 receptors and seems to have an anti-apoptotic effect on these cells.

  12. Interleukin-4 and interleukin-10 modulate nuclear factor kappaB activity and nitric oxide synthase-2 expression in Theiler's virus-infected brain astrocytes.

    Science.gov (United States)

    Molina-Holgado, Eduardo; Arévalo-Martín, Angel; Castrillo, Antonio; Boscá, Lisardo; Vela, José M; Guaza, Carmen

    2002-06-01

    In brain astrocytes, nuclear factor kappaB (NF-kappaB) is activated by stimuli that produce cellular stress causing the expression of genes involved in defence, including the inducible nitric oxide synthase (NOS-2). Theiler's murine encephalomyelitis virus (TMEV) induces a persistent CNS infection and chronic immune-mediated demyelination, similar to human multiple sclerosis. The cytokines interleukin (IL)-4 and IL-10 inhibit the expression of proinflammatory cytokines, counteracting the inflammatory process. Our study reports that infection of cultured astrocytes with TMEV resulted in a time-dependent phosphorylation of IkappaBalpha, degradation of IkappaBalpha and IkappaBbeta, activation of NF-kappaB and expression of NOS-2. The proteasome inhibitor MG-132 blocked TMEV-induced nitrite accumulation, NOS-2 mRNA expression and phospho-IkappaBalpha degradation, suggesting NF-kappaB-dependent NOS-2 expression. Pretreatment of astrocytes with IL-4 or IL-10 decreased p65 nuclear translocation, NF-kappaB binding activity and NOS-2 transcription. IL-4 and IL-10 caused an accumulation of IkappaBalpha in TMEV-infected astrocytes without affecting IkappaBbeta levels. The IkappaB kinase activity and the degradation rate of both IkappaBs were not modified by either cytokine, suggesting de novo synthesis of IkappaBalpha. Indeed, IL-4 or IL-10 up-regulated IkappaBalpha mRNA levels after TMEV infection. Therefore, the accumulation of IkappaBalpha might impair the translocation of the NF-kappaB to the nucleus, mediating the inhibition of NF-kappaB activity. Overall, these data suggest a novel mechanism of action of IL-4 and IL-10, which abrogates NOS-2 expression in viral-infected glial cells.

  13. Adenine nucleotides inhibit proliferation of the human lung adenocarcinoma cell line LXF-289 by activation of nuclear factor kappaB1 and mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Schäfer, Rainer; Hartig, Roland; Sedehizade, Fariba; Welte, Tobias; Reiser, Georg

    2006-08-01

    Extracellular nucleotides have a profound role in the regulation of the proliferation of diseased tissue. We studied how extracellular nucleotides regulate the proliferation of LXF-289 cells, the adenocarcinoma-derived cell line from human lung bronchial tumor. ATP and ADP strongly inhibited LXF-289 cell proliferation. The nucleotide potency profile was ATP = ADP = ATPgammaS > > UTP, UDP, whereas alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, 2',3'-O-(4-benzoylbenzoyl)-ATP, AMP and UMP were inactive. The nucleotide potency profile and the total blockade of the ATP-mediated inhibitory effect by the phospholipase C inhibitor U-73122 clearly show that P2Y receptors, but not P2X receptors, control LXF-289 cell proliferation. Treatment of proliferating LXF-289 cells with 100 microm ATP or ADP induced significant reduction of cell number and massive accumulation of cells in the S phase. Arrest in S phase is also indicated by the enhancement of the antiproliferative effect of ATP by coapplication of the cytostatic drugs cisplatin, paclitaxel and etoposide. Inhibition of LXF-289 cell proliferation by ATP was completely reversed by inhibitors of extracellular signal related kinase-activating kinase/extracellular signal related kinase 1/2 (PD98059, U0126), p38 mitogen-activated protein kinase (SB203508), phosphatidylinositol-3-kinase (wortmannin), and nuclear factor kappaB1 (SN50). Western blot analysis revealed transient activation of p38 mitogen-activated protein kinase, extracellular signal-related kinase 1/2, and nuclear factor kappaB1 and possibly new formation of p50 from its precursor p105. ATP-induced attenuation of LXF-289 cell proliferation was accompanied by transient translocation of p50 nuclear factor kappaB1 and extracellular signal-related kinase 1/2 to the nucleus in a similar time period. In summary, inhibition of LXF-289 cell proliferation is mediated via P2Y receptors by activation of multiple mitogen-activated protein kinase pathways and nuclear

  14. Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Local Osteoporotic Canine Mandible Model for the Evaluation of Peri-Implant Bone Regeneration.

    Science.gov (United States)

    Chang, Ah Ryum; Cho, Tae Hyung; Hwang, Soon Jung

    2017-08-24

    The canine mandible is useful for studying bone regeneration after dental implant placement. However, it is limited in investigations of peri-implant osteogenesis under osteoporotic conditions due to the insignificant osteoporotic effect of ovariectomy. This study aimed at establishing a local osteoporotic model without ovariectomy by using receptor activator of nuclear factor kappa-B ligand (RANKL) in a canine mandible model. This new model was used to evaluate the effects of injectable β-tricalcium phosphate (TCP) microsphere bone grafts on peri-implant bone regeneration under osteoporotic conditions with combinations of recombinant human bone morphogenetic protein-2 (rhBMP-2). A local osteoporotic canine mandible model was designed by creating a hole in the mandibular alveolar bone, then implanting a collagen sponge soaked with 20, 40, or 60 μg RANKL into the hole, and leaving it for 2 weeks. After the establishment of the dose for maximum osteoporotic bone loss at 40 μg of RANKL, the main surgery was performed. RANKL-soaked collagen sponges were removed, and dental implants were placed with bone grafts in five groups: implant only, TCP, and TCP + rhBMP-2 at 5, 15, and 45 μg. Peri-implant bone generation was determined by radiologic and histologic evaluations at 6 weeks after dental implant placement. On performing micro-computed tomography analysis, the group with TCP + 5 μg rhBMP-2 showed the highest bone volume than the other groups and a 22% increase (p model was useful for peri-implant bone regeneration under osteoporotic conditions such as those found in geriatric patients. The injectable β-TCP bone grafts used in this study were effective in peri-implant bone generation under osteoporotic conditions, and their efficiency was enhanced at 5 μg BMP-2 compared with higher concentrations of BMP-2.

  15. Inhibition of tumor necrosis factor-alpha-induced interleukin-6 expression by telmisartan through cross-talk of peroxisome proliferator-activated receptor-gamma with nuclear factor kappaB and CCAAT/enhancer-binding protein-beta.

    Science.gov (United States)

    Tian, Qingping; Miyazaki, Ryohei; Ichiki, Toshihiro; Imayama, Ikuyo; Inanaga, Keita; Ohtsubo, Hideki; Yano, Kotaro; Takeda, Kotaro; Sunagawa, Kenji

    2009-05-01

    Telmisartan, an angiotensin II type 1 receptor antagonist, was reported to be a partial agonist of peroxisome proliferator-activated receptor-gamma. Although peroxisome proliferator-activated receptor-gamma activators have been shown to have an anti-inflammatory effect, such as inhibition of cytokine production, it has not been determined whether telmisartan has such effects. We examined whether telmisartan inhibits expression of interleukin-6 (IL-6), a proinflammatory cytokine, in vascular smooth muscle cells. Telmisartan, but not valsartan, attenuated IL-6 mRNA expression induced by tumor necrosis factor-alpha (TNF-alpha). Telmisartan decreased TNF-alpha-induced IL-6 mRNA and protein expression in a dose-dependent manner. Because suppression of IL-6 mRNA expression was prevented by pretreatment with GW9662, a specific peroxisome proliferator-activated receptor-gamma antagonist, peroxisome proliferator-activated receptor-gamma may be involved in the process. Telmisartan suppressed IL-6 gene promoter activity induced by TNF-alpha. Deletion analysis suggested that the DNA segment between -150 bp and -27 bp of the IL-6 gene promoter that contains nuclear factor kappaB and CCAAT/enhancer-binding protein-beta sites was responsible for telmisartan suppression. Telmisartan attenuated TNF-alpha-induced nuclear factor kappaB- and CCAAT/enhancer-binding protein-beta-dependent gene transcription and DNA binding. Telmisartan also attenuated serum IL-6 level in TNF-alpha-infused mice and IL-6 production from rat aorta stimulated with TNF-alpha ex vivo. These data suggest that telmisartan may attenuate inflammatory process induced by TNF-alpha in addition to the blockade of angiotensin II type 1 receptor. Because both TNF-alpha and angiotensin II play important roles in atherogenesis through enhancement of vascular inflammation, telmisartan may be beneficial for treatment of not only hypertension but also vascular inflammatory change.

  16. Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization

    NARCIS (Netherlands)

    Kuznetsova, T.; Wang, S.Y.; Rao, N.A.; Mandoli, A.; Martens, J.H.; Rother, N; Aartse, A.; Groh, L.; Janssen-Megens, E.M.; Li, G.; Ruan, Y.; Logie, C.; Stunnenberg, H.G.

    2015-01-01

    BACKGROUND: The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by

  17. Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo.

    Science.gov (United States)

    Baek, Jong Min; Kim, Ju-Young; Ahn, Sung-Jun; Cheon, Yoon-Hee; Yang, Miyoung; Oh, Jaemin; Choi, Min Kyu

    2016-03-01

    Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects of DM on bone diseases such as osteoporosis. Thus, we investigated the relationship between DM and osteoclasts, cells that function in bone resorption. We found that DM significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation; DM directly induced the down-regulation of c-Fos and nuclear factor of activated T cells c1 (NFATc1) without affecting other RANKL-dependent transduction pathways. In the later stages of osteoclast maturation, DM negatively regulated the organization of filamentous actin (F-actin), resulting in impaired bone-resorbing activity by the mature osteoclasts. In addition, micro-computed tomography (μ-CT) analysis of the murine model revealed that DM had a beneficial effect on lipopolysaccharide (LPS)-mediated bone erosion. Histological analysis showed that DM attenuated the degradation of trabecular bone matrix and formation of TRAP-positive osteoclasts in bone tissues. These results suggest that DM is a potential candidate for the treatment of metabolic bone disorders such as osteoporosis.

  18. Phytochemicals of Aristolochia tagala and Curcuma caesia exert anticancer effect by tumor necrosis factor-α-mediated decrease in nuclear factor kappaB binding activity

    OpenAIRE

    Hadem, Khetbadei Lysinia Hynniewta; Sharan, Rajeshwar Nath; Kma, Lakhan

    2015-01-01

    Rationale: The active compounds or metabolites of herbal plants exert a definite physiological action on the human body and thus are widely used in human therapy for various diseases including cancer. Previous studies by our group have reported the anticarcinogenic properties of the two herbal plants extracts (HPE) of Aristolochia tagala (AT) Cham. and Curcuma caesia (CC) Roxb. in diethylnitrosamine-induced mouse liver cancer in vivo. The anticarcinogenic properties of these extracts may be d...

  19. Antiosteoclastogenesis activity of a CO2 laser antagonizing receptor activator for nuclear factor kappaB ligand-induced osteoclast differentiation of murine macrophages

    Science.gov (United States)

    Kuo, Chun-Liang; Kao, Chia-Tze; Fang, Hsin-Yuan; Huang, Tsui-Hsien; Chen, Yi-Wen; Shie, Ming-You

    2015-03-01

    Macrophage cells are the important effector cells in the immune reaction which are indispensable for osteoclastogenesis; their heterogeneity and plasticity renders macrophages a primer target for immune system modulation. In recent years, there have been very few studies about the effects of macrophage cells on laser treatment-regulated osteoclastogenesis. In this study, RAW 264.7 macrophage cells were treated with RANKL to regulate osteoclastogenesis. We used a CO2 laser as a model biostimulation to investigate the role of osteoclastogenic. We also evaluated cell viability, cell death and cathepsin K expression. The CO2 laser inhibited a receptor activator of the NF-ĸB ligand (RANKL)-induced formation of osteoclasts during the osteoclast differentiation process. It was also found that irradiation for two times reduced RANKL-enhanced TRAP activity in a dose-dependent manner. Furthermore, CO2 laser-treatment diminished the expression and secretion of cathepsin K elevated by RANKL and was concurrent with the inhibition of TRAF6 induction and NF-ĸB activation. The current report demonstrates that CO2 laser abrogated RANKL-induced osteoclastogenesis by retarding osteoclast differentiation. The CO2 laser can modulate every cell through dose-dependent in vitro RANKL-mediated osteoclastogenesis, such as the proliferation and fusion of preosteoclasts and the maturation of osteoclasts. Therefore, the current results serve as an improved explanation of the cellular roles of macrophage cell populations in osteoclastogenesis as well as in alveolar bone remodeling by CO2 laser-treatment.

  20. Expression and localization of peroxisome proliferator-activated receptors and nuclear factor kappaB in normal and lesional psoriatic skin

    DEFF Research Database (Denmark)

    Westergaard, Majken; Henningsen, Jeanette; Johansen, Claus

    2003-01-01

    activators of PPARdelta. The expression levels of NF-kappaB p50 and p65 were not significantly altered in lesional compared with nonlesional psoriatic skin. In the basal layer of normal epidermis both p50 and p65 were sequestered in the cytoplasm, whereas p50, but not p65, localized to nuclei...... in the suprabasal layers, and this distribution was maintained in lesional psoriatic skin. In normal human keratinocytes PPAR agonists neither impaired IL-1beta-induced translocation of p65 nor IL-1beta-induced NF-kappaB DNA binding. We show that PPARdelta physically interacts with the N-terminal Rel homology......-mediated transactivation was partially relieved by forced expression of the coactivators p300 or CBP. We suggest that deficient NF-kappaB activation in chronic psoriatic plaques permitting unabated PPARdelta-mediated transactivation contributes to the pathologic phenotype of psoriasis....

  1. Inhibition of nuclear factor kappa-B signaling reduces growth in medulloblastoma in vivo

    Directory of Open Access Journals (Sweden)

    Deckard Lindsey A

    2011-04-01

    Full Text Available Abstract Background Medulloblastoma is a highly malignant pediatric brain tumor that requires surgery, whole brain and spine irradiation, and intense chemotherapy for treatment. A more sophisticated understanding of the pathophysiology of medulloblastoma is needed to successfully reduce the intensity of treatment and improve outcomes. Nuclear factor kappa-B (NFκB is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Methods To test the importance of NFκB to medulloblastoma cell growth, the effects of multiple drugs that inhibit NFκB, pyrrolidine dithiocarbamate, diethyldithiocarbamate, sulfasalazine, curcumin and bortezomib, were studied in medulloblastoma cell lines compared to a malignant glioma cell line and normal neurons. Expression of endogenous NFκB was investigated in cultured cells, xenograft flank tumors, and primary human tumor samples. A dominant negative construct for the endogenous inhibitor of NFκB, IκB, was prepared from medulloblastoma cell lines and flank tumors were established to allow specific pathway inhibition. Results We report high constitutive activity of the canonical NFκB pathway, as seen by Western analysis of the NFκB subunit p65, in medulloblastoma tumors compared to normal brain. The p65 subunit of NFκB is extremely highly expressed in xenograft tumors from human medulloblastoma cell lines; though, conversely, the same cells in culture have minimal expression without specific stimulation. We demonstrate that pharmacological inhibition of NFκB in cell lines halts proliferation and leads to apoptosis. We show by immunohistochemical stain that phosphorylated p65 is found in the majority of primary tumor cells examined. Finally, expression of a dominant negative form of the endogenous inhibitor of NFκB, dnIκB, resulted in poor xenograft tumor growth, with average tumor volumes

  2. Esculetin attenuates receptor activator of nuclear factor kappa-B ligand-mediated osteoclast differentiation through c-Fos/nuclear factor of activated T-cells c1 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Jong Min; Park, Sun-Hyang; Cheon, Yoon-Hee; Ahn, Sung-Jun [Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Lee, Myeung Su [Division of Rheumatology, Department of Internal Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Oh, Jaemin, E-mail: jmoh@wku.ac.kr [Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kim, Ju-Young, E-mail: kimjy1014@gmail.com [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2015-05-29

    Esculetin exerts various biological effects on anti-oxidation, anti-tumors, and anti-inflammation. However, the involvement of esculetin in the bone metabolism process, particularly osteoclast differentiation has not yet been investigated. In the present study, we first confirmed the inhibitory effect of esculetin on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. We then revealed the relationship between esculetin and the expression of osteoclast-specific molecules to elucidate its underlying mechanisms. Esculetin interfered with the expression of c-Fos and nuclear factor of activated T cell c1 (NFATc1) both at the mRNA and protein level with no involvement in osteoclast-associated early signaling pathways, suppressing the expression of various transcription factors exclusively expressed in osteoclasts such as tartrate-resistant acid phosphatase (Trap), osteoclast-associated receptor (Oscar), dendritic cell-specific transmembrane protein (Dcstamp), osteoclast stimulatory transmembrane protein (Ocstamp), cathepsin K, αvβ3 integrin, and calcitonin receptor (Ctr). Additionally, esculetin inhibited the formation of filamentous actin (F-actin) ring-positive osteoclasts during osteoclast differentiation. However, the development of F-actin structures and subsequent bone resorbing activity of mature osteoclasts, which are observed in osteoclast/osteoblast co-culture systems were not affected by esculetin. Taken together, our results indicate for the first time that esculetin inhibits RANKL-mediated osteoclastogenesis via direct suppression of c-Fos and NFATc1 expression and exerts an inhibitory effect on actin ring formation during osteoclastogenesis. - Highlights: • We first investigated the effects of esculetin on osteoclast differentiation and function. • Our data demonstrate for the first time that esculetin can suppress osteoclastogenesis in vitro. • Esculetin acts as an inhibitor of c-Fos and NFATc1 activation.

  3. Expression of osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, tumor necrosis factor-related apoptosis-inducing ligand, stromal cell-derived factor-1 and their receptors in epithelial metastatic breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Labovsky Vivian

    2012-06-01

    Full Text Available Abstract Background While breast cancer (BC is the major cause of death among women worldwide, there is no guarantee of better patient survival because many of these patients develop primarily metastases, despite efforts to detect it in its early stages. Bone metastasis is a common complication that occurs in 65-80 % of patients with disseminated disease, but the molecular basis underlying dormancy, dissemination and establishment of metastasis is not understood. Our objective has been to evaluate simultaneously osteoprotegerin (OPG, receptor activator of nuclear factor kappa B ligand (RANKL, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, stromal cell-derived factor-1 (SDF-1, and their receptors (R in 2 human BC cell lines, MDA-MB-231 and MCF-7. Methods OPG, RANKL, TRAIL and SDF-1 expression and release, in addition to the expression of their receptors has been investigated using immunofluorescence, immunocytochemistry and ELISA analyses. Results MCF-7 cells released higher levels of OPG in conditioned media (CM than MDA-MB-231 cells; 100 % of both types of cell expressed OPG, RANKL, TRAIL and SDF-1. Moreover, 100 % in both lines expressed membrane RANKL and RANK, whereas only 50 % expressed CXCR4. Furthermore, 100 % expressed TRAIL-R1 and R4, 30-50 % TRAIL-R2, and 40-55 % TRAIL-R3. Conclusions MCF-7 and MDA-MB-231 cells not only released OPG, but expressed RANKL, TRAIL and SDF-1. The majority of the cells also expressed RANK, CXCR4 and TRAIL-R. Since these ligands and their receptors are implicated in the regulation of proliferation, survival, migration and future bone metastasis during breast tumor progression, assessment of these molecules in tumor biopsies of BC patients could be useful in identifying patients with more aggressive tumors that are also at risk of bone metastasis, which may thus improve the available options for therapeutic intervention.

  4. Role of Nuclear Factor kappaB in Intestine Injury Induced by Hepatic Ischemia Reperfusion

    Institute of Scientific and Technical Information of China (English)

    陈俊华; 王国斌

    2004-01-01

    Summary: The role of nuclear factor kappaB in intestine injury induced by hepatic ischemia reperfusion was investigated. Eighteen male Wistar rats were divided into 3 groups randomly: sham operation group (group A), hepatic ischemia reperfusion group (group B) and hepatic ischemia reperfusion plus pyrrolidine dithiocarbamate (PDTC) group (group C). The rats in group A were only subjected to laparotomy, those in group B underwent partial hepatic ischemia reperfusion (ischemia for 1 h and reperfusion for 2 h) and those in group C underwent the same procedure as that of group B but received PDTC 200 mg/kg i.v. before and after ischemia. After reperfusion, tissues of jejunum and venous blood were obtained for measurement of TNF-α, MDA and MPO. The levels of TNF-α in jejunum and venous blood, the levels of MPO in jejunum in group B were significantly higher than those in group A and group C (P<0.05). There was no significant different in the levels of MDA between group B and group C. The severity of histological intestinal injury in group B and group C was similar. Hepatic ischemia reperfusion caused intestine injury, NF-kappaB may play an important role in this course and the targeting of upstream components of the inflammatory response, such as NF-kappaB, may have important therapeutic applications.

  5. Structure-activity relationship studies of chalcone leading to 3-hydroxy-4,3',4',5'-tetramethoxychalcone and its analogues as potent nuclear factor kappaB inhibitors and their anticancer activities.

    Science.gov (United States)

    Srinivasan, Balasubramanian; Johnson, Thomas E; Lad, Rahul; Xing, Chengguo

    2009-11-26

    Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.

  6. Statistics of assay validation in high throughput cell imaging of nuclear factor kappaB nuclear translocation.

    Science.gov (United States)

    Morelock, Maurice M; Hunter, Edward A; Moran, Timothy J; Heynen, Susanne; Laris, Casey; Thieleking, Michael; Akong, Michael; Mikic, Ivana; Callaway, Scott; DeLeon, Rodney P; Goodacre, Angela; Zacharias, David; Price, Jeffrey H

    2005-10-01

    This report describes statistical validation methods implemented on assay data for inhibition of subcellular redistribution of nuclear factor kappaB (NF kappaB) in HeLa cells. We quantified cellular inhibition of cytoplasmic-nuclear translocation of NF kappaB in response to a range of concentrations of interleukin-1 (IL-1) receptor antagonist in the presence of IL-1alpha using eight replicate rows in each four 96-well plates scanned five times on each of 2 days. Translocation was measured as the fractional localized intensity of the nucleus (FLIN), an implementation of our more general fractional localized intensity of the compartments (FLIC), which analyzes whole compartments in the context of the entire cell. The NF kappaB antagonist assay (inhibition of IL-1- induced NF kappaB translocation) data were collected on a Q3DM (San Diego, CA) EIDAQtrade mark 100 high throughput microscopy system. [In 2003, Q3DM was purchased by Beckman Coulter Inc. (Fullerton, CA), which released the IC 100 successor to the EIDAQ 100.] The generalized FLIC method is described along with two-point (minimum-maximum) and multiple point titration statistical methods. As a ratio of compartment intensities that tend to change proportionally, FLIN was resistant to photobleaching errors. Two-point minimum-maximum statistical analyses yielded the following: a Z' of 0.174 with the data as n = 320 independent well samples; Z' by row data in a range of 0.393-0.933, with a mean of 0.766; by-plate Z' data of 0.310, 0.443, 0.545, and 0.794; and by-plate means of columns Z' data of 0.879, 0.927, 0.945, and 0.963. The mean 50% inhibitory concentration (IC50) for IL-1 receptor antagonist over all experiments was 213 ng/ml. The combined IC50 coefficients of variation (CVs) were 0.74%, 0.85%, 2.09%, and 2.52% for the four plates. Repeatability IC50 CVs were as follows: day to day 3.0%, row to row 8.0%, plate to plate 2.8%, and day to day 0.6%. The number of cells required for statistically resolvable

  7. Tumor necrosis factor alpha induces spermidine/spermine N1-acetyltransferase through nuclear factor kappaB in non-small cell lung cancer cells.

    Science.gov (United States)

    Babbar, Naveen; Hacker, Amy; Huang, Yi; Casero, Robert A

    2006-08-25

    Tumor necrosis factor alpha (TNFalpha) is a potent pleiotropic cytokine produced by many cells in response to inflammatory stress. The molecular mechanisms responsible for the multiple biological activities of TNFalpha are due to its ability to activate multiple signal transduction pathways, including nuclear factor kappaB (NFkappaB), which plays critical roles in cell proliferation and survival. TNFalpha displays both apoptotic and antiapoptotic properties, depending on the nature of the stimulus and the activation status of certain signaling pathways. Here we show that TNFalpha can lead to the induction of NFkappaB signaling with a concomitant increase in spermidine/spermine N(1)-acetyltransferase (SSAT) expression in A549 and H157 non-small cell lung cancer cells. Induction of SSAT, a stress-inducible gene that encodes a rate-limiting polyamine catabolic enzyme, leads to lower intracellular polyamine contents and has been associated with decreased cell growth and increased apoptosis. Stable overexpression of a mutant, dominant negative IkappaBalpha protein led to the suppression of SSAT induction by TNFalpha in these cells, thereby substantiating a role of NFkappaB in the induction of SSAT by TNFalpha. SSAT promoter deletion constructs led to the identification of three potential NFkappaB response elements in the SSAT gene. Electromobility shift assays, chromatin immunoprecipitation experiments and mutational studies confirmed that two of the three NFkappaB response elements play an important role in the regulation of SSAT in response to TNFalpha. The results of these studies indicate that a common mediator of inflammation can lead to the induction of SSAT expression by activating the NFkappaB signaling pathway in non-small cell lung cancer cells.

  8. Involvement of nuclear factor {kappa}B in platelet CD40 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Hachem, Ahmed [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Yacoub, Daniel [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Zaid, Younes [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Mourad, Walid [Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Merhi, Yahye, E-mail: yahye.merhi@icm-mhi.org [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Given that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo

  9. Effects of ketamine on proinflammatory cytokines and nuclear factor kappaB in polyrnicrobial sepsis rats

    Institute of Scientific and Technical Information of China (English)

    Xue-Min Song; Jian-Guo Li; Yan-Lin Wang; Qing Zhou; Zhao-Hui Du; Bao-Hui Jia; Jian-Juan Ke

    2006-01-01

    AIM: To explore the effects of ketamine on hemodynamics, plasma proinflammatory cytokine (TNF-α and IL-6) levels and nuclear factor kappa B (NF-κB) activation during polymicrobial sepsis.METHODS: Male Sprague-Dawlay rats were subjected to cecal ligation and puncture (CLP) or sham operation.The rats were randomly assigned into four equal groups:sham CLP group, CLP group, ketamine (KT)I groupand KTⅡ group. Thirty minutes before CLP, ketamine (5my/kg per hour and 10 my/kg per hour, respectively) was infused continuously through the left femoral vein cannula in KT I group or KTⅡgroup. Sham CLP group and CLP group received 0.9% saline only (5 mL/kg per hour). The right femoral artery was cannulated to monitor mean arterial pressure (MAP) and heart rates (HR),and draw blood samples. The proinflammatory cytokine (TNF-α and IL-6) levels of plasma were measured using enzyme-linked immunosorbent assays (ELISA). The hepatic NF-κB activation was determined by Western blot and HPIAS 2000 image analysis system.Twenty hours after CLP, the rats were killed by right femoral artery phlebotomization.RESULTS: CLP produced progressive hypotension,and a first increase followed by a decrease in HR. The hypotension was prevented, and the HR was slightly steady in ketamine treated rats. TNF-α levels of plasma reached a peak value at 2 h after CLP. Ketamine (KT I group or KTⅡgroup) caused a significant decrease compared with CLP group at 2, 5 and 9 h time points after CLP (14.3 ± 1.9 vs 4.3 ± 0.9, 9.7 ± 1.4 vs 4.3 ±0.9; 9.3 ± 1.5 vs 4.3 ± 0.9, 8.7 ± 1.4 vs 4.3 ± 0.9; 6.0± 1.5 vs 5.0 ± 1.7, 5.3 ± 0.8 vs 5.0 ± 1.7; P < 0.01,respectively). The IL-6 levels of plasma firstly ascended and then descended in CLP group, and reached a peak value at 9 h after CLP. Ketamine (KT I group or KTⅡ group) caused a significant decrease compared with CLP group at 5, 9 or 20 h after CLP (135.0 ± 52.6 vs 60.0± 16.3, 112.5 ± 52.6 vs 60.0 ± 16.3; 410.0 ± 68.7 vs62.5 ± 12.5, 250.0

  10. Nuclear factor kappa-B signaling is integral to ocular neovascularization in ischemia-independent microenvironment.

    Directory of Open Access Journals (Sweden)

    Michael DeNiro

    Full Text Available Retinal ischemia promotes the upregulation of VEGF expression and accounts for most pathological features of retinal neovascularization (NV. Paradoxically, VEGF remains the pivotal stimulator of ocular NV, despite the absence of ischemia. Therefore, the central question arises as to how the various molecular mechanisms interplay in ischemia-independent NV. It's been suggested that NFκB plays a crucial role in the pathogenesis of diabetic vasculopathies. Here, we dissected the molecular mechanism of ocular NV in the rho/VEGF transgenic mouse model, which develops subretinal NV in ischemia-independent microenvironment. Furthermore, we examined whether intravitreal administration of YC-1, a HIF-1 inhibitor, can modulate the activation of NFκB and its downstream angiogenic signaling in the mouse retina. We demonstrated that YC-1 inhibited retinal NFκB/p65 DNA binding activity and downregulated NFκB/p65, FAK, α5β1, EPO, ET-1, and MMP-9 expression at the message and the protein levels. In addition, YC-1 significantly inhibited subretinal NV by reducing the number of neovascular lesions, the area of each lesion and the total area of NV per retina. We further investigated the influence of VEGF signaling pathway on HIF-1α transcriptional activity to substantiate that this mouse model develops subretinal NV in an ischemia-independent microenvironment. Our data demonstrated that VEGF overexpression didn't have any impact on HIF-1α transcriptional activity, whereas treatment with YC-1 significantly inhibited endogenous HIF-1 activity. Our study suggests that retinal NFκB transcriptional activity is pivotal to ischemia-independent mechanisms, which lead to the local activation of angiogenic cascades. Our data also indicate that the nexus between VEGF and NFκB is implicated in triggering the angiogenic cascade that promotes retinal NV. Hence, targeting the VEGF/NFκB axis may act in a negative feedback loop to suppress ocular NV. This study suggests

  11. The Nuclear Factor kappaB Inhibitor Pyrrolidine Dithiocarbamate Prevents Cardiac Remodelling and Matrix Metalloproteinase-2 Up-Regulation in Renovascular Hypertension.

    Science.gov (United States)

    Cau, Stefany B A; Guimaraes, Danielle A; Rizzi, Elen; Ceron, Carla S; Gerlach, Raquel F; Tanus-Santos, Jose E

    2015-10-01

    Imbalanced matrix metalloproteinase (MMP) activity is involved in hypertensive cardiac hypertrophy. Pharmacological inhibition of nuclear factor kappaB (NF-кB) with pyrrolidine dithiocarbamate (PDTC) can prevent MMP up-regulation. We suggested that treatment with PDTC could prevent 2-kidney, 1-clip (2K1C) hypertension-induced left ventricular remodelling. Sham-operated controls or 2K1C rats with hypertension received either vehicle or PDTC (100 mg/kg/day) by gavage for 8 weeks. Systolic blood pressure was monitored every week. Histological assessment of left ventricles was carried out with haematoxylin/eosin sections, and fibrosis was quantified in picrosirius red-stained sections. Oxidative stress was evaluated in heart samples with the dihydroethidium probe. Cardiac MMP activity was determined by in situ zymography, and cardiac MMP-2 was assessed by immunofluorescence. 2K1C surgery significantly increased systolic blood pressure in the 2K1C vehicle. PDTC exerted antihypertensive effects after 2 weeks of treatment. Histology revealed increased left ventricular and septum wall thickness associated with augmented myocyte diameter in hypertensive rats, which were reversed by treatment with PDTC. Hypertensive rats developed pronounced cardiac fibrosis with increased interstitial collagen area, increased cardiac reactive oxygen species levels, gelatinase activity and MMP-2 expression. PDTC treatment decreased these alterations. These findings show that PDTC modulates myocardial MMP-2 expression and ameliorates cardiac remodelling in renovascular hypertension. These results suggest that interfering with MMP expression at transcriptional level may be an interesting strategy in the therapy of organ damage associated with hypertension.

  12. Effects of systemic immunogenic insults and circulating proinflammatory cytokines on the transcription of the inhibitory factor kappaB alpha within specific cellular populations of the rat brain.

    Science.gov (United States)

    Laflamme, N; Rivest, S

    1999-07-01

    Expression of the inhibitory factor kappaB alpha (IkappaB alpha) reflects the activity of nuclear factor kappaB(NF-kappaB) and is a powerful tool to investigate the regulation of the transcription factor within the CNS. IkappaB alpha mRNA was evaluated in the rat brain by means of in situ hybridization following different immunogenic stimuli; i.e., intraperitoneal (i.p.) and intravenous (i.v.) lipopolysaccharide (LPS), i.v. recombinant rat interleukin (IL) 1beta, IL-6, or tumor necrosis factor-alpha (TNF-alpha), and intramuscular (i.m.) turpentine injection, used here as a model of systemic localized inflammatory insult. Systemic LPS, IL-1beta, and TNF-alpha caused a rapid and transient transcriptional activation of IkappaB alpha along the blood vessels of the entire brain; the signal was very intense 30-60 min after the i.v. injections and returned to undetectable levels from 2 to 12 h depending on the challenge. Double-labeling procedure provided the anatomical evidence that IkappaB alpha-expressing cells within the microvasculature were essentially of the endothelial type, as they were immunoreactive to the von Willebrand factor. Scattered small cells were also found across the brain of LPS-, IL-1beta-, and TNF-alpha-injected rats at time 1-3 h, and microglial (OX-42)-immunoreactive cells were positive for the transcript. Such expression within parenchymal microglia was nevertheless not observed in the brain following a localized and sterile inflammatory insult. Indeed, i.m. turpentine administration stimulated IkappaB alpha transcription quite uniquely within the endothelium of the brain capillaries, an effect that paralleled the swelling of the injection site and lasted up to 24 h after the aggression. In contrast to these immunogenic challenges, i.v. IL-6 injection failed to activate the gene encoding IkappaB alpha in the rat brain. These results indicate that NF-kappaB may play a crucial role in specific cellular populations of the CNS to trigger

  13. The Nuclear Factor kappaB Pathway: A Link to the Immune System in the Radiation Response

    Science.gov (United States)

    Hellweg, Christine; Baumstark-Khan, Christa; Reitz, Guenther; Chishti, Arif Ali; Koch, Kristina; Manchanda, Kashish

    Understanding the cellular radiation response is an essential prerequisite for the risk assessment of astronauts’ space radiation exposure during long-term space missions and for effective countermeasure development. In addition to the space radiation effects, other environmental factors during space missions such as microgravity have profound effects on the body, e.g. suppression of the innate and acquired immune response. Exposure to ionizing radiation modulates immune responses in a complex dose-dependent pattern, with possible anti-inflammatory effects in the low dose range, expression of pro-inflammatory cytokines at moderate doses and immunosuppression after exposure to higher doses due to precursor cell death together with concomitant exacerbated innate immune responses. A central regulator in the immune system is the transcription factor Nuclear Factor kB (NF-kappaB). In this work, the role of NF-kappaB in the cellular response to space relevant radiation qualities was analyzed. It was shown with a recombinant human NF-kappaB reporter cell line that heavy ions with a linear energy transfer (LET) of 100-300 keV/µm have a nine times higher potential to activate the NF-kappaB pathway compared to X-rays (150 kV). ATM was essential for NF-kappaB activation in response to X-rays and heavy ions. Knockdown of the NF-kappaB subunit RelA (p65) resulted in higher sensitivity towards X-rays. Reverse Transcriptase real-time quantitative PCR (RT-qPCR) experiments showed that after exposure to radiation, NF-kappaB predominantly upregulates genes involved in intercellular communication processes, especially genes coding for chemokines, suggesting an important contribution of NF-kappaB in the molecular profile of the reaction to radiation, which can comprise features of inflammation and wound healing processes. This is process is strictly NF-kappaB dependent as this response is completely absent in RelA knockdown cells. These results show that the role of NF-kappaB in

  14. Radiation induced nuclear factor kappa-B signaling cascade study in mammalian cells by improved detection systems

    Science.gov (United States)

    Chishti, Arif Ali; Baumstark-Khan, Christa; Hellweg, Christine; Reitz, Guenther

    To enable long-term human space flight cellular radiation response to densely ionizing radiation needs to be better understood for developing appropriate countermeasures to mitigate acute effects and late radiation risks for the astronaut. The biological effectiveness of accelerated heavy ions with high linear energy transfer (LET) for effecting DNA damage response pathways as a gateway to cell death or survival is of major concern, not only for tumor radiotherapy but also for new regimes of space missions. Ionizing radiation modulates several signaling pathways resulting in transcription factor activation. NF-kappaB is one of the important transcription factors that respond to changes in the environment of a mammalian cell and plays a key role in many biological processes relevant to radiation response, such as apoptosis, inflammation and carcinogenesis. From medical and biological point of view it is important to understand radiation induced NF-kappaB signaling cascade. For studying NF-kappaB signaling, green fluorescent proteins EGFP and d2EGFP were used previously (Advances in Space Research, 36: 1673-1679, 2005). The current study aims to improve reporter assays by the use of a destabilized variant of red fluorescent protein tdTomato (DD-tdTomato) which gives high fluorescence signals and a better signal/noise ratio for NF-kappaB activation. The reporter system HEK-pNFkappaB-DD-tdTomato-C8 is a dual reporter system which can provide both discrete and cumulative signals after exposure to ionizing radiation (X-rays, heavy ions). In the presence of Shield-1, the fluorescent protein DD-tdTomato is not degraded but accumulated inside the cell which helps to quantify the fold induction of NF-kappaB-dependent gene expression. The minimum dose required to activate NF-kappaB is 6 Gy but accumulated signals data shows that NF-kappaB is activated after 3 Gy in the presence of Shield-1. Average dose and number of heavy ions’ hits per nucleus necessary to double the NF

  15. Effects of L-3-n-butylphthalide on caspase-3 and nuclear factor kappa-B expression in primary basal forebrain and hippocampal cultures after beta-amyloid peptide 1-42 treatment

    Institute of Scientific and Technical Information of China (English)

    Ruixia Wang; Yong Zhang; Liangliang Jiang; Guozhao Ma; Qingxi Fu; Jialong Li; Peng Yan; Lunqian Shen; Yabo Feng; Chunxia Li; Zaiying Pang; Yuanxiao Cui; Chunfu Chen; Yifeng Du; Zhaokong Liu

    2009-01-01

    BACKGROUND: L-3-n-butylphthalide (L-NBP) can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 (Aβ1-42).OBJECTIVE: To observe the neuroprotective effects of L-NBP on caspase-3 and nuclear factor kappa-B (NF-кB) expression in a rat model of Alzheimer's disease.DESIGN, TIME AND SETTING: A cell experiment was performed at the Central Laboratory of Provincial Hospital affiliated to Shandong University between January 2008 and August 2008.MATERIALS: L-NBP (purity>98%) was provided by Shijiazhuang Pharma Group NBP Pharmaceutical Company Limited. Aβ1-42, 3-[4,5-dimethylthiazolo-2]-2,5 iphenyltetrazolium bromide (MTT), and rabbit anti-Caspase-3 polyclonal antibody were provided by Cell Signaling, METHODS: Primary cultures were generated from rat basal forebrain and hippocampal neurons at 17 or 19 days of gestation. The cells were assigned into five groups: the control group, the Aβ1-42 group (2μmol/L), the Aβ1-42+0.1μmol/L L-NBP group, the Aβ1-42+1 μmol/L L-NBP group, and the Aβ1-42 + 10μmol/L L-NBP group. The neurons were treated with Aβ1-42 (2 μmol/L) alone or in combination with L-NBP (0.1, 1, 10μmol/L) for 48 hours. Cells in the control group were incubated in PBS.MAIN OUTCOME MEASURES: Morphologic changes were evaluated using inverted microscopy, Western blot.RESULTS: Induction with Aβ1-42 for 48 hours caused cell death and soma atrophy, and increased the high dose (P<0.05).CONCLUSION: Aβ1-42 is toxic to basal forebrain and hippocampal primary neurons; L-NBP protects against this toxicity and inhibits the induction of caspase-3 and NF-κB expression.

  16. Osteoprotegerin and ligand of receptor activator of nuclear factor : kappaB expression in ovariectomized rats during tooth movement

    NARCIS (Netherlands)

    Tan, Lijun; Ren, Yijin; Wang, Jun; Jiang, Lingyong; Cheng, Hui; Sandham, John; Zhao, Zhihe

    2009-01-01

    Objective: To test the null hypothesis that increased tooth displacement in ovariectomized rats is not related to differential expressions of OPG and RANKL in the periodontium. Materials and Methods: Eighty-four 12-week female rats were used; half were ovariectomized and half were not. Three months

  17. Osteoprotegerin and ligand of receptor activator of nuclear factor : kappaB expression in ovariectomized rats during tooth movement

    NARCIS (Netherlands)

    Tan, Lijun; Ren, Yijin; Wang, Jun; Jiang, Lingyong; Cheng, Hui; Sandham, John; Zhao, Zhihe

    Objective: To test the null hypothesis that increased tooth displacement in ovariectomized rats is not related to differential expressions of OPG and RANKL in the periodontium. Materials and Methods: Eighty-four 12-week female rats were used; half were ovariectomized and half were not. Three months

  18. Osteoprotegerin and ligand of receptor activator of nuclear factor : kappaB expression in ovariectomized rats during tooth movement

    NARCIS (Netherlands)

    Tan, Lijun; Ren, Yijin; Wang, Jun; Jiang, Lingyong; Cheng, Hui; Sandham, John; Zhao, Zhihe

    2009-01-01

    Objective: To test the null hypothesis that increased tooth displacement in ovariectomized rats is not related to differential expressions of OPG and RANKL in the periodontium. Materials and Methods: Eighty-four 12-week female rats were used; half were ovariectomized and half were not. Three months

  19. NF kappaB expression increases and CFTR and MUC1 expression decreases in the endometrium of infertile patients with hydrosalpinx: a comparative study

    Directory of Open Access Journals (Sweden)

    Song Yong

    2012-10-01

    Full Text Available Abstract Background Hydrosalpinx are associated with infertility, due to reduced rates of implantation and increased abortion rates. The aims of this study were to investigate the expression of cystic fibrosis transmembrane conductance regulator (CFTR, nuclear factor kappa B (NF KappaB and mucin-1 (MUC-1, and analyze the correlation between the expression of CFTR and NF KappaB or MUC1, in the endometrium of infertile women with and without hydrosalpinx. Methods Thirty-one infertile women with laparoscopy-confirmed unilateral or bilateral hydrosalpinx and 20 infertile women without hydrosalpinx or pelvic inflammatory disease (control group were recruited. Endometrial biopsy samples were collected and the expression of CFTR, NF KappaB and MUC1 were analyzed using immunohistochemistry and quantitative real-time PCR. Results CFTR, NF KappaB and MUC1 mRNA and protein expression tended to increase in the secretory phase compared to the proliferative phase in both groups; however, these differences were not significantly different. The endometrium of infertile patients with hydrosalpinx had significantly higher NF KappaB mRNA and protein expression, and significantly lower CFTR and MUC1 mRNA and protein expression, compared to control infertile patients. A positive correlation was observed between CFTR and MUC1 mRNA expression (r = 0.65, P CFTR mRNA and NF KappaB mRNA expression (r = −0.59, P Conclusions Increased NF KappaB expression and decreased CFTR and MUC1 expression in the endometrium of infertile patients with hydrosalpinx reinforce the involvement of a molecular mechanism in the regulation of endometrial receptivity.

  20. Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.

    Science.gov (United States)

    Sriwijitkamol, Apiradee; Christ-Roberts, Christine; Berria, Rachele; Eagan, Phyllis; Pratipanawatr, Thongchai; DeFronzo, Ralph A; Mandarino, Lawrence J; Musi, Nicolas

    2006-03-01

    Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is not known whether IkappaB/NFkappaB signaling in muscle from subjects with type 2 diabetes is abnormal. We studied IkappaB/NFkappaB signaling in vastus lateralis muscle from six subjects with type 2 diabetes and eight matched control subjects. Muscle from type 2 diabetic subjects was characterized by a 60% decrease in IkappaB beta protein abundance, an indicator of increased activation of the IkappaB/NFkappaB pathway. IkappaB beta abundance directly correlated with insulin-mediated glucose disposal (Rd) during a hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp (r = 0.63, P = 0.01), indicating that increased IkappaB/NFkappaB pathway activity is associated with muscle insulin resistance. We also investigated whether reversal of this abnormality could be a mechanism by which training improves insulin sensitivity. In control subjects, 8 weeks of aerobic exercise training caused a 50% increase in both IkappaB alpha and IkappaB beta protein. In subjects with type 2 diabetes, training increased IkappaB alpha and IkappaB beta protein to levels comparable with that of control subjects, and these increments were accompanied by a 40% decrease in tumor necrosis factor alpha muscle content and a 37% increase in insulin-stimulated glucose disposal. In summary, subjects with type 2 diabetes have reduced IkappaB protein abundance in muscle, suggesting excessive activity of the IkappaB/NFkappaB pathway. Moreover, this abnormality is reversed by exercise training.

  1. Skeletal changes in osteoprotegerin and receptor activator of nuclear factor-kappab ligand mRNA levels in primary hyperparathyroidism: effect of parathyroidectomy and association with bone metabolism

    DEFF Research Database (Denmark)

    Stilgren, L S; Rettmer, E; Eriksen, E F;

    2004-01-01

    (PHPT), hypersecretion of PTH leads to enhanced bone resorption and formation with increased risk of fracture. Decreasing PTH levels by surgery normalizes bone metabolism, but the effects on skeletal OPG and RANKL production are unknown. In this study, 24 patients referred to our clinic for evaluation...

  2. Inhibition of the nuclear factor kappa B (NF-kappa B) pathway by tetracyclic kaurene diterpenes in macrophages. Specific effects on NF-kappa B-inducing kinase activity and on the coordinate activation of ERK and p38 MAPK.

    Science.gov (United States)

    Castrillo, A; de Las Heras, B; Hortelano, S; Rodriguez, B; Villar, A; Bosca, L

    2001-05-11

    The anti-inflammatory action of most terpenes has been explained in terms of the inhibition of nuclear factor kappaB (NF-kappaB) activity. Ent-kaurene diterpenes are intermediates of the synthesis of gibberellins and inhibit the expression of NO synthase-2 and the release of tumor necrosis factor-alpha in J774 macrophages challenged with lipopolysaccharide. These diterpenes inhibit NF-kappaB and IkappaB kinase (IKK) activation in vivo but failed to affect in vitro the function of NF-kappaB, the phosphorylation and targeting of IkappaBalpha, and the activity of IKK-2. Transient expression of NF-kappaB-inducing kinase (NIK) activated the IKK complex and NF-kappaB, a process that was inhibited by kaurenes, indicating that the inhibition of NIK was one of the targets of these diterpenes. These results show that kaurenes impair the inflammatory signaling by inhibiting NIK, a member of the MAPK kinase superfamily that interacts with tumor necrosis factor receptor-associated factors, and mediate the activation of NF-kappaB by these receptors. Moreover, kaurenes delayed the phosphorylation of p38, ERK1, and ERK2 MAPKs, but not that of JNK, in response to lipopolysaccharide treatment of J774 cells. The absence of a coordinate activation of MAPK and IKK might contribute to a deficient activation of NF-kappaB that is involved in the anti-inflammatory activity of these molecules.

  3. RelA NF-κB subunit activation as a therapeutic target in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Zhang, Mingzhi; Xu-Monette, Zijun Y; Li, Ling;

    2016-01-01

    It has been well established that nuclear factor kappa-B (NF-κB) activation is important for tumor cell growth and survival. RelA/p65 and p50 are the most common NF-kB subunits and involved in the classical NF-kB pathway. However, the prognostic and biological significance of RelA/p65 is equivoca...

  4. Psychosocial factors underlying physical activity

    Directory of Open Access Journals (Sweden)

    Ji Cheng-Ye

    2007-09-01

    of physical activity on academic achievement and other factors beyond physical health; barriers of not having enough time and having too many assignments perceived to hinder frequent physical activity; and parental approval. More rigorous research on psychosocial determinants with close-ended items developed from these open-ended data and with larger sample sizes of students is necessary. Research with parents and school staff will be needed to understand the perceptions of these stakeholder groups key to creating the students' social environment.

  5. Nuclear Factor {kappa}B, Airway Epithelium, and Asthma: Avenues for Redox Control

    NARCIS (Netherlands)

    Janssen-Heininger, Y.M.; Poynter, M.E.; Aesif, S.W.; Pantano, C.; Ather, J.L.; Reynaert, N.L.; Ckless, K.; Anathy, V.; van der Velden, J.; Irvin, C.G.; van der Vliet, A.

    2009-01-01

    A wealth of recent studies points to the importance of airway epithelial cells in the orchestration of inflammatory responses in the allergic inflamed lung. Studies also point to a role of oxidative stress in the pathophysiology of chronic inflammatory diseases. This article provides a perspective

  6. PRMT5, a novel TRAIL receptor-binding protein, inhibits TRAIL-induced apoptosis via nuclear factor-kappaB activation.

    Science.gov (United States)

    Tanaka, Hiroshi; Hoshikawa, Yutaka; Oh-hara, Tomoko; Koike, Sumie; Naito, Mikihiko; Noda, Tetsuo; Arai, Hiroyuki; Tsuruo, Takashi; Fujita, Naoya

    2009-04-01

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily and has selective antitumor activity. Although TNF-alpha-induced intracellular signaling pathways have been well studied, TRAIL signaling is not fully understood. Here, we identified a novel TRAIL receptor-binding protein, protein arginine methyltransferase 5 (PRMT5), as a result of proteomic screening. PRMT5 selectively interacted with death receptor 4 and death receptor 5 but not with TNF receptor 1 or Fas. PRMT5 gene silencing sensitized various cancer cells to TRAIL without affecting TRAIL resistance in nontransformed cells. PRMT5 contributed to TRAIL-induced activation of inhibitor of kappaB kinase (IKK) and nuclear factor-kappaB (NF-kappaB), leading to induction of several NF-kappaB target genes. Although IKK inhibition increased sensitivity to both TRAIL and TNF-alpha, PRMT5 knockdown potentiated TRAIL-mediated cytotoxicity alone. PRMT5 had no effect on TNF-alpha-mediated NF-kappaB signaling. These results show the selectivity of PRMT5 for TRAIL signaling. The PRMT5 small interfering RNA-mediated susceptibility to TRAIL was rescued by ectopic expression of active IKKbeta, confirming the involvement of PRMT5 in TRAIL resistance by activating the NF-kappaB pathway. Collectively, our findings suggest the therapeutic potential of PRMT5 in TRAIL-based cancer treatments

  7. Differential effects of black raspberry and strawberry extracts on BaPDE-induced activation of transcription factors and their target genes.

    Science.gov (United States)

    Li, Jingxia; Zhang, Dongyun; Stoner, Gary D; Huang, Chuanshu

    2008-04-01

    The chemopreventive properties of edible berries have been demonstrated both in vitro and in vivo, however, the specific molecular mechanisms underlying their anti-cancer effects are largely unknown. Our previous studies have shown that a methanol extract fraction of freeze-dried black raspberries inhibits benzoapyrene (BaP)-induced transformation of Syrian hamster embryo cells. This fraction also blocks activation of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB) induced by benzoapyrene diol-epoxide (BaPDE) in mouse epidermal JB6 Cl 41 cells. To determine if different berry types exhibit specific mechanisms for their anti-cancer effects, we compared the effects of extract fractions from both black raspberries and strawberries on BaPDE-induced activation of various signaling pathways in Cl 41 cells. Black raspberry fractions inhibited the activation of AP-1, NF-kappaB, and nuclear factor of activated T cells (NFAT) by BaPDE as well as their upstream PI-3K/Akt-p70(S6K) and mitogen-activated protein kinase pathways. In contrast, strawberry fractions inhibited NFAT activation, but did not inhibit the activation of AP-1, NF-kappaB or the PI-3K/Akt-p70(S6K) and mitogen-activated protein kinase pathways. Consistent with the effects on NFAT activation, tumor necrosis factor-alpha (TNF-alpha) induction by BaPDE was blocked by extract fractions of both black raspberries and strawberries, whereas vascular endothelial growth factor (VEGF) expression, which depends on AP-1 activation, was suppressed by black raspberry fractions but not strawberry fractions. These results suggest that black raspberry and strawberry components may target different signaling pathways in exerting their anti-carcinogenic effects.

  8. Phillyrin, a natural lignan, attenuates tumor necrosis factor α-mediated insulin resistance and lipolytic acceleration in 3T3-L1 adipocytes.

    Science.gov (United States)

    Kong, Poren; Zhang, Linlin; Guo, Yuyu; Lu, Yingli; Lin, Dongping

    2014-07-01

    In obese adipose tissue, tumor necrosis factor-α secreted from macrophages plays an important role in the adipocyte dysfunctions, including insulin resistance, lipolytic acceleration, and changes of adipokines, which promote the development of obesity-related complications. Phillyrin, an active ingredient found in many medicinal plants and certain functional foods, elicits anti-obesity and anti-inflammatory properties in vivo. The aim of the current study was to investigate the role of phillyrin in preventing tumor necrosis factor α-induced insulin resistance or lipolytic acceleration in 3T3-L1 adipocytes. Our results showed that phillyrin partially restored insulin-stimulated 2-DOG uptake, which was reduced by tumor necrosis factor-α, with concomitant restoration in serine phosphorylation of insulin receptor substrate-1 and insulin-stimulated Glut4 translocation to plasma membrane. Phillyrin also dose-dependently prevented tumor necrosis factor α-stimulated adipocyte lipolysis with preserved downregulation of perilipin. The mitogen-activated protein kinases and I kappaB kinase activation was promoted in tumor necrosis factor α-stimulated adipocytes, but pretreatment with 40 µM phillyrin inhibited the phosphorylation of extracellular signal-regulated kinases1/2, stress-activated protein kinase/Jun N-terminal kinase and I kappaB kinase (padipocytes and RAW 264.7 macrophages, the enhanced productions of tumor necrosis factor-α and free fatty acids in the medium were significantly reduced by phillyrin (padipocyte dysfunctions induced by tumor necrosis factor-α through suppression of the activation of I kappaB kinase and N-terminal kinase. Phillyrin may have the potential to ameliorate the inflammatory changes and insulin resistance in obese adipose tissue. Georg Thieme Verlag KG Stuttgart · New York.

  9. Activity factors of the Korean exposure factors handbook.

    Science.gov (United States)

    Jang, Jae-Yeon; Jo, Soo-Nam; Kim, So-Yeon; Lee, Kyung-Eun; Choi, Kyung-Ho; Kim, Young-Hee

    2014-01-01

    Exposure factors based on the Korean population are required for making appropriate risk assessment. It is expected that handbooks for exposure factors will be applied in many fields, as well as by health department risk assessors. The present article describes the development of an exposure factors handbook that specifically focuses on human activities in situations involving the possible risk of exposure to environmental contaminants. We define majour exposure factors that represent behavioral patterns for risk assessment, including time spent on routine activities, in different places, on using transportation, and engaged in activities related to water contact including swimming, bathing and washing. Duration of residence and employment are also defined. National survey data were used to identify recommended levels of exposure factors in terms of time spent on routine activities and period of residence and employment. An online survey was conducted with 2073 subjects who were selected using a stratified random sampling method in order to develop a list of exposure factors for the time spent in different places and in performing water-related activities. We provide the statistical distribution of the variables, and report reference levels of average exposure based on the reliable data in our exposure factors handbook.

  10. Nuclear factor-kappaB activation on the reactive oxygen species in acute necrotizing pancreatitic rats

    Institute of Scientific and Technical Information of China (English)

    Jin Long; Na Song; Xi-Ping Liu; Ke-Jian Guo; Ren-Xuan Guo

    2005-01-01

    AIM: To investigate the potential role of nuclear factor kappa-B (NF-κB) activation on the reactive oxygen species in rat acute necrotizing pancreatitis (ANP) and to assess the effect of pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB).METHODS: Rat ANP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. Rats were randomly assigned to three groups (10rats each): Control group, ANP group and PDTC group. At the 6th h of the model, the changes of the serum amylase,nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and pancreatic morphological damage were observed. The expressions of inducible nitric oxide (iNOS) were observed by SP immunohistochemistry. And the expressions of NF-κB p65 subunit mRNA were observed by hybridization in situ.RESULTS: Serum amylase and NO level decreased significantly in ANP group as compared with PDTC administrated group [(7 170.40±1 308.63) U/L vs(4 074.10±1 719.78) U/L,P<0.05], [(76.95±9.04) μmol/L vs (65.18±9.02) μmol/L,P<0.05] respectively. MDA in both ANP and PDTC group rose significantly over that in control group [(9.88±1.52)nmol/L, (8.60±1.41) nmol/L, vs (6.04±1.78) nmol/L,P<0.05], while there was no significant difference between them. SOD levels in both ANP and PDTC group underwent a significant decrease as compared with that in control [(3 214.59±297.74) NU/mL, (3 260.62±229.44) NU/mL,vs (3 977.80±309.09) NU/mL, P<0.05], but there was no significant difference between them. Though they were still higher than those in Control group, pancreas destruction was slighter in PDTC group, iNOS expression and NF-κB p65 subunit mRNA expression were lower in PDTC group as compared with ANP group.CONCLUSION: We conclude that correlation among NF-κB activation, serum amylase, reactive oxygen species level and tissue damage suggests a key role of NF-κB in the pathogenesis of ANP. Inhibition of NF-κB activation may reverse the pancreatic damage

  11. Coagulation factor VIII activity in diabetic patients

    Directory of Open Access Journals (Sweden)

    Nermina Babić

    2011-02-01

    Full Text Available Aim To examine coagulation factor VIII activity in plasma, as a risk factor for thrombosis, in the patients with diabetes mellitus (DM. Also, to assess its relationship with ibrinogen and fasting blood glucose concentrations and with body mass index. Methods The plasma coagulation factor VIII activity, plasma levels of ibrinogen and blood glucose concentrations were measured in 30 patients with DM type 1, 30 patients with DM type 2 and in 30 healthy subjects. Body weight and body height were also measured and BMI was calculated.Results The plasma factor VIII activity in patients with DM type 1 and patients with DM type 2 was signiicantly higher than the values measured in healthy subjects. There was no signiicant difference in the factor VIII activity between patients with DM type 1 and type 2. The concentrations of ibrinogen and blood glucose in both groups of patients were signiicantly higher than in the group of healthy subjects. Patients with DM type 2 had a signiicantly higher BMI compared to healthy subjects, as well as compared to patients with DM type 1. There was a signiicant positive correlation between plasma factor VIII activity and plasma level of ibrinogen and a signiicant negative correlation between factor VIII activity and BMI in patients with DM type 2. Conclusion Diabetic patients have the elevated plasma coagulation factor VIII activity and increased ibrinogen concentration thus an increased risk of thrombosis and vascular diseases.

  12. AGRO100 inhibits activation of nuclear factor-kappaB (NF-kappaB) by forming a complex with NF-kappaB essential modulator (NEMO) and nucleolin.

    Science.gov (United States)

    Girvan, Allicia C; Teng, Yun; Casson, Lavona K; Thomas, Shelia D; Jüliger, Simone; Ball, Mark W; Klein, Jon B; Pierce, William M; Barve, Shirish S; Bates, Paula J

    2006-07-01

    AGRO100, also known as AS1411, is an experimental anticancer drug that recently entered human clinical trials. It is a member of a novel class of antiproliferative agents known as G-rich oligonucleotides (GRO), which are non-antisense, guanosine-rich phosphodiester oligodeoxynucleotides that form stable G-quadruplex structures. The biological activity of GROs results from their binding to specific cellular proteins as aptamers. One important target protein of GROs has been previously identified as nucleolin, a multifunctional protein expressed at high levels by cancer cells. Here, we report that AGRO100 also associates with nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO), which is a regulatory subunit of the inhibitor of kappaB (IkappaB) kinase (IKK) complex, and also called IKKgamma. In the classic NF-kappaB pathway, the IKK complex is required for phosphorylation of IkappaBalpha and subsequent activation of the transcription factor NF-kappaB. We found that treatment of cancer cells with AGRO100 inhibits IKK activity and reduces phosphorylation of IkappaBalpha in response to tumor necrosis factor-alpha stimulation. Using a reporter gene assay, we showed that AGRO100 blocks both tumor necrosis factor-alpha-induced and constitutive NF-kappaB activity in human cancer cell lines derived from cervical, prostate, breast, and lung carcinomas. In addition, we showed that, in AGRO100-treated cancer cells, NEMO is coprecipitated by nucleolin, indicating that both proteins are present in the same complex. Our studies suggest that abrogation of NF-kappaB activity may contribute to the anticancer effects of AGRO100 and that nucleolin may play a previously unknown role in regulating the NF-kappaB pathway.

  13. Key factors of enterprise innovation activity

    Directory of Open Access Journals (Sweden)

    Pichugina Maryna Anatoliivna

    2015-02-01

    Full Text Available The article deals with the studies of factors and conditions that define enterprise innovative activity. It is distinguished factors that influence the orientation on innovation of a company and factors that influence the innovation ability. It is noted an interdependence between innovative ability, orientation and activity. The article is also dedicated to analyses of influence specific industry characteristics and inner view of enterprise. It is discussed the influence of such factors as knowledge base, the organizational learning mechanisms, an external openness and the structure of innovative connections on the company opportunities to innovate. It is tried to focus on the impact of the environment on enterprise capabilities.

  14. Mitogen-activated protein kinase 3/mitogen-activated protein kinase 1 activates apoptosis during testicular ischemia-reperfusion injury in a nuclear factor-kappaB-independent manner.

    Science.gov (United States)

    Minutoli, Letteria; Antonuccio, Pietro; Polito, Francesca; Bitto, Alessandra; Squadrito, Francesco; Di Stefano, Vincenzo; Nicotina, Piero Antonio; Fazzari, Carmine; Maisano, Daniele; Romeo, Carmelo; Altavilla, Domenica

    2009-02-14

    Nuclear factor kappa-B (NF-kappaB), mitogen-activated protein kinase3/MAPK1 and MAPK8 are involved in testicular ischemia reperfusion injury (testicular-I/R). NF-kappaB knock-out mice (KO) subjected to testicular-I/R have a reduced testicular damage, blunted MAPK8 activation and enhanced MAPK3/MAPK1 activity. To better understand the role of MAPK3/MAPK1 up-regulation during testicular-I/R, we investigated the effects of PD98059, an inhibitor of MAPK3/MAPK1, in KO mice during testicular-I/R. KO and wild-type (WT) animals underwent 1 h testicular ischemia followed by 24 h reperfusion or a sham testicular-I/R. Animals received either PD98059 (5 mg/kg/ip) or its vehicle. MAPK3/MAPK1, BAX, caspase-3 and -9 and TNF-alpha expression were assessed along with histological examination and an immunostaining for protein of apoptosis. Testicular-I/R caused a greater increase in MAPK3/MAPK1 in KO than in WT animals in both testes. KO mice had a lower expression of the apoptotic proteins and TNF-alpha as well as reduced histological damage compared to WT. Immunostaining confirmed the lower expression of BAX in the Leydig cells of KO mice. Administration of PD98059, abrogated MAPK3/MAPK1 expression and slightly reduced TNF-alpha but did not improve or reverse the histological damage in KO. PD98059 significantly reduced the histological damage in WT mice and markedly reduced the apoptotic proteins in KO and WT mice. These results suggest that testicular-I/R triggers also a pathway of organ damage involving MAPK3/MAPK1, TNF-alpha, BAX, caspase-3 and -9 that activates an apoptotic machinery in an NF-kappaB independent manner. These findings should contribute to better understand testicular torsion-induced damage.

  15. Involvement of mitogen-activated protein kinases (MAPKs) during testicular ischemia-reperfusion injury in nuclear factor-kappaB knock-out mice.

    Science.gov (United States)

    Minutoli, Letteria; Antonuccio, Pietro; Polito, Francesca; Bitto, Alessandra; Fiumara, Tiziana; Squadrito, Francesco; Nicotina, Piero Antonio; Arena, Salvatore; Marini, Herbert; Romeo, Carmelo; Altavilla, Domenica

    2007-07-12

    Nuclear factor kappa-B (NF-kappaB), extracellular regulated kinase (ERK 1/2) and c-jun-N terminal kinase (JNK) play an important role in testicular ischemia. We investigated the patterns of ERK1/2, JNK and p38 activation in NF-kappaB knockout (KO) mice subjected to testicular torsion. KO and normal littermate wild-type (WT) animals underwent at 1 h testicular ischemia followed by 24 h reperfusion (TI/R). Sham testicular ischemia-reperfusion mice served as controls. ERK 1/2, JNK and p38 expression by western blot analysis, tumor necrosis factor-alpha (TNF-alpha) expression (RT-PCR and western blot analysis) and a complete histological examination were carried out. TI/R caused a greater increase in phosphorylated form of ERK 1/2 in KO mice than in WT animals in either the ischemic testis and the contralateral one. By contrary, active form of JNK and p38 were completely abrogated in both testes of KO mice, while WT animals showed a significant activation of those kinases in both testes. TNF-alpha expression was markedly reduced in KO mice when compared to WT mice either at the mRNA and the protein level. Finally TI/R-induced histological damage was markedly reduced in KO mice. Our data indicate that NF-kappaB plays a pivotal role in the development of testicular ischemia-reperfusion injury and suggest that, in the absence of the transcriptional factor, the up-stream signal JNK and p38 may be abrogated while ERK 1/2 activity is enhanced.

  16. Unemployment as a factor of entrepreneurial activity

    Directory of Open Access Journals (Sweden)

    Sebastian Șipoș-Gug

    2012-12-01

    Full Text Available We aim to investigate the nature and direction of the relationship between unemployment and entrepreneurial activity. Our research, using monthly data from Romania (1991-2012, brings evidence to the hypothesis that the relationship is non-linear in regard to the temporal delay factor. From our data it would seem that unemployment and entrepreneurial activity are negatively related on the short term, and positively related on the long term. Based on these results, we propose that the two effects be treated separately, and we propose two predictive models of entrepreneurial activity based on unemployment that follow this distinction.

  17. Atividade inflamatória em mucosa de reservatório ileal na polipose adenomatosa familiar e retocolite ulcerativa inespecífica: avaliação da expressão de TNF-alfa e IL-1beta, e da ativação NF- kapaB Inflammatory activity in pelvic ileal pouches for familial adenomatous polyposis and ulcerative colitis: expression of TNF-alpha, IL-1beta and the activation of NF- kappaB

    Directory of Open Access Journals (Sweden)

    Raquel Franco Leal

    2006-12-01

    Full Text Available A ileíte do reservatório pós retocolectomia total constitui uma das complicações mais comuns nos doentes com RCUI, apresentando pequena freqüência nos doentes com PAF. OBJETIVO: Avaliar a atividade inflamatória em mucosa de reservatórios ileais endoscopicamente normais, através da expressão de TNF-alfa, NF-kapaB e IL-1beta. CASUÍSTICA E MÉTODOS: Selecionaram-se 20 doentes submetidos à retocolectomia total com reservatório ileal em "J" pelo Grupo de Coloproctologia da UNICAMP, sendo 10 doentes com RCUI e 10 com PAF. O grupo controle foi constituído por íleo terminal de intestino normal. Realizadas biópsias da mucosa do reservatório ileal e do íleo terminal normal, e congeladas em nitrogênio líquido. A expressão de TNF-alfa e IL-1beta foi analisada por extrato total e de NF-kB por meio de imunoprecipitado. A separação protéica foi feita por eletroforese em gel de poliacrilamida. RESULTADOS: Expressão de TNF-alfa e IL-1beta apresentaram níveis maiores nos doentes com RCUI, quando comparados àqueles com PAF (p0.1 e IL-1beta (p > 0.05 sem diferença estatística em relação aos demais grupos. CONCLUSÃO: Os doentes com RCUI apresentaram maiores níveis de expressão das citocinas estudadas, mesmo sem evidência clínica e endoscópica de ileíte do reservatório, podendo justificar maior suscetibilidade dos doentes com RCUI a esta complicação.Pouchitis after total retocolectomy is one of the most common complication of patients with ulcerative colitis (UC, while its frequency is quite rare in familial adenomatous polyposis (FAP. PURPOSE: To evaluate the inflammatory activity in endoscopicaly normal mucosa of the ileal pouch, by determining the expression of TNF-alpha and IL-1beta, and the activation of NF-kappaB. METHODS AND PATIENTS: Twenty patients with "J" pouch after total retocolectomy were studied, being 10 patients with UC and 10 with FAP. The control group was constituted by biopsies from terminal ileum take

  18. [Status of the osteoclast-activating system in cosmonauts after long-duration missions to the International Space Station].

    Science.gov (United States)

    Morukov, I B; Rykova, M P; Antropova, E N; Berendeeva, T A; Ponomarev, S A; Morukov, B V

    2014-01-01

    The results of studying the system of osteoprotegerin/ receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) in 22 cosmonauts after long-duration (124 to 199 days) ISS missions are presented. Immediately on return to 1 g, changes were observed in OPG and RANKL serum levels and the ability to produce unstimulated and stimulated PGA of peripheral blood mononuclear cells in vitro. Individual variability of these changes was noticed. Our findings suggest that the cytokine OPG/RANKL-system is involved in bone remodeling in members of long-duration space missions.

  19. Selenium Deficiency Attenuates Chicken Duodenal Mucosal Immunity via Activation of the NF-κb Signaling Pathway.

    Science.gov (United States)

    Liu, Zhe; Qu, Yanpeng; Wang, Jianfa; Wu, Rui

    2016-08-01

    Selenium (Se) deficiency can cause intestinal mucosal inflammation, which is related to activation of nuclear transcription factor kappa-B (NF-κB) signaling pathway. However, the mechanism of inflammatory response in chicken duodenal mucosa caused by Se deficiency and its relationship with the NF-κB signaling pathway remain elusive. In this study, we firstly obtained Se-deficient chickens bred with 0.01 mg/kg Se and the normal chickens bred with 0.4 mg/kg Se for 35 days. Then, NF-κB signaling pathway, secretory immunoglobulin A (SIgA), inflammatory cytokines, oxidized glutathione, glutathione peroxidase, and glutathione activities were determined. The results showed that Se deficiency obviously enhanced p50, p65, and p65 DNA-binding activities. The phosphorylation of IκB-α and phosphorylation of kappa-B kinase subunit alpha (IKKα) and IKKα were elevated, but IκB-α was decreased (P mucosal immunity via activation of NF-κB signaling pathway regulated by redox activity, which suggested that Se is a crucial host factor involved in regulating inflammation.

  20. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  1. Epicatechin induces NF-kappaB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling in HepG2 cells.

    Science.gov (United States)

    Granado-Serrano, Ana Belén; Martín, María Angeles; Haegeman, Guy; Goya, Luis; Bravo, Laura; Ramos, Sonia

    2010-01-01

    The dietary flavonoid epicatechin has been reported to exhibit a wide range of biological activities. The objective of the present study was to investigate the time-dependent regulation by epicatechin on the activity of the main transcription factors (NF-kappaB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor (Nrf2)) related to antioxidant defence and survival and proliferation pathways in HepG2 cells. Treatment of cells with 10 microm-epicatechin induced the NF-kappaB pathway in a time-dependent manner characterised by increased levels of IkappaB kinase (IKK) and phosphorylated inhibitor of kappaB subunit-alpha (p-IkappaBalpha) and proteolytic degradation of IkappaB, which was consistent with an up-regulation of the NF-kappaB-binding activity. Time-dependent activation of the AP-1 pathway, in concert with enhanced c-Jun nuclear levels and induction of Nrf2 translocation and phosphorylation were also demonstrated. Additionally, epicatechin-induced NF-kappaB and Nrf2 were connected to reactive oxygen species intracellular levels and to the activation of cell survival and proliferation pathways, being phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) associated to Nrf2 modulation and ERK to NF-kappaB induction. These data suggest that the epicatechin-induced survival effect occurs by the induction of redox-sensitive transcription factors through a tight regulation of survival and proliferation pathways.

  2. Requirement for caspase-8 in NF-kappaB activation by antigen receptor.

    Science.gov (United States)

    Su, Helen; Bidère, Nicolas; Zheng, Lixin; Cubre, Alan; Sakai, Keiko; Dale, Janet; Salmena, Leonardo; Hakem, Razqallah; Straus, Stephen; Lenardo, Michael

    2005-03-04

    Caspase-8, a proapoptotic protease, has an essential role in lymphocyte activation and protective immunity. We show that caspase-8 deficiency (CED) in humans and mice specifically abolishes activation of the transcription factor nuclear factor kappaB (NF-kappaB) after stimulation through antigen receptors, Fc receptors, or Toll-like receptor 4 in T, B, and natural killer cells. Caspase-8 also causes the alphabeta complex of the inhibitor of NF-kappaB kinase (IKK) to associate with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex. Recruitment of the IKKalpha, beta complex, its activation, and the nuclear translocation of NF-kappaB require enzyme activity of full-length caspase-8. These findings thus explain the paradoxical association of defective apoptosis and combined immunodeficiency in human CED.

  3. A20 is a negative regulator of BCL10- and CARMA3-mediated activation of NF-kappaB.

    Science.gov (United States)

    Stilo, Romania; Varricchio, Ettore; Liguoro, Domenico; Leonardi, Antonio; Vito, Pasquale

    2008-04-15

    The molecular complex containing CARMA proteins, BCL10 and TRAF6 has been identified recently as a key component in the signal transduction pathways that regulate activation of the nuclear factor kappaB (NF-kappaB) transcription factor. Here, we report that the inducible protein A20 negatively regulates these signaling cascades by means of its deubiquitylation activity. We show that A20 perturbs assembly of the complex containing CARMA3, BCL10 and IKKgamma/NEMO, thereby suppressing activation of NF-kappaB. Together, our results further define the molecular mechanisms that control activation of NF-kappaB and reveal a function for A20 in the regulation of CARMA and BCL10 activity in lymphoid and non-lymphoid cells.

  4. Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway.

    Science.gov (United States)

    Zhang, Xiang-An; Zhang, Shuangxi; Yin, Qing; Zhang, Jing

    2015-01-01

    Quercetin can inhibit the growth of cancer cells with the ability to act as chemopreventers. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. Nuclear factor kappa-B (NF-κB) is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Inhibitors of NF-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in colon cancer. In this study, we demonstrate that quercetin induces apoptosis in human colon cancer CACO-2 and SW-620 cells through inhibiting NF-κB pathway, as well as down-regulation of B-cell lymphoma 2 and up-regulation of Bax, thus providing basis for clinical application of quercetin in colon cancer cases.

  5. Physical activity and cardiovascular disease risk factors among ...

    African Journals Online (AJOL)

    We assessed level physical activity and its relationship with CVD risk factors among ... Anthropometric measurements, blood pressure, fasting blood glucose and ... Conclusion: Physical activity energy expenditure was high in this population ...

  6. Active Von Willebrand Factor, thrombocytopenia and thrombosis

    NARCIS (Netherlands)

    Hulstein, J.J.J.

    2006-01-01

    Platelets and von Willebrand factor (VWF) are unable to interact in circulation. To induce an interaction, a conversion of VWF to a platelet-binding conformation is required. At higher shear stresses, the first step in thrombus formation is binding of VWF to the subendothelium. This results in expos

  7. Ecological Factors Improving Efficiency of Business Activities

    Directory of Open Access Journals (Sweden)

    Kononova G. A.

    2015-01-01

    Full Text Available The economic importance of optimizing the environmental situation from the perspective of an entrepreneur are assessed in the article. The classification of administrative decisions taken in the course of the business activities is proposed. The authors identified a group of solutions directly providing optimization of environment external to the enterprise, solutions that have an indirect positive impact on the environment and solutions that improve ecology of industrial premises. The nature of economic effect of resulting solutions of various types is taken into account. Vectors of influence of working conditions on the economic results of business activities are described. The nature and strength of the impact of model management decisions results of business activities are defined. Key performance indicators of entrepreneurial activity are identified: employee productivity, the amount of revenue and profitability, solvency, staff stability, the competitiveness of enterprises. Grouping the costs of ecological parameters optimization of the production environment is proposed. Relationship between level of working conditions and socio-psychological climate in the collective enterprise is disclosed. The methods of motivation of entrepreneurs in solving of environmental, production problems are considered. The role of training entrepreneurs engaged of medium and small businesses are underlined especially. Thus, in the article the relationship between environmental and economic problems of entrepreneurial activity is investigated. Role and opportunities of entrepreneurs in solving these problems are defined and structured.

  8. The Dishevelled, EGL-10 and pleckstrin (DEP domain-containing protein DEPDC7 binds to CARMA2 and CARMA3 proteins, and regulates NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Egildo Luca D'Andrea

    Full Text Available The molecular complexes containing BCL10, MALT1 and CARMA proteins (CBM complex have been recently identified as a key component in the signal transduction pathways that regulate activation of Nuclear Factor kappaB (NF-κB transcription factor. Herein we identified the DEP domain-containing protein DEPDC7 as cellular binding partners of CARMA2 and CARMA3 proteins. DEPDC7 displays a cytosolic distribution and its expression induces NF-κB activation. Conversely, shRNA-mediated abrogation of DEPDC7 results in impaired NF-κB activation following G protein-coupled receptors stimulation, or stimuli that require CARMA2 and CARMA3, but not CARMA1. Thus, this study identifies DEPDC7 as a CARMA interacting molecule, and provides evidence that DEPDC7 may be required to specifically convey on the CBM complex signals coming from activated G protein-coupled receptors.

  9. The Dishevelled, EGL-10 and pleckstrin (DEP) domain-containing protein DEPDC7 binds to CARMA2 and CARMA3 proteins, and regulates NF-κB activation.

    Science.gov (United States)

    D'Andrea, Egildo Luca; Ferravante, Angela; Scudiero, Ivan; Zotti, Tiziana; Reale, Carla; Pizzulo, Maddalena; De La Motte, Luigi Regenburgh; De Maio, Chiara; Mazzone, Pellegrino; Telesio, Gianluca; Vito, Pasquale; Stilo, Romania

    2014-01-01

    The molecular complexes containing BCL10, MALT1 and CARMA proteins (CBM complex) have been recently identified as a key component in the signal transduction pathways that regulate activation of Nuclear Factor kappaB (NF-κB) transcription factor. Herein we identified the DEP domain-containing protein DEPDC7 as cellular binding partners of CARMA2 and CARMA3 proteins. DEPDC7 displays a cytosolic distribution and its expression induces NF-κB activation. Conversely, shRNA-mediated abrogation of DEPDC7 results in impaired NF-κB activation following G protein-coupled receptors stimulation, or stimuli that require CARMA2 and CARMA3, but not CARMA1. Thus, this study identifies DEPDC7 as a CARMA interacting molecule, and provides evidence that DEPDC7 may be required to specifically convey on the CBM complex signals coming from activated G protein-coupled receptors.

  10. Factors influencing beta-amylase activity in sorghum malt

    CSIR Research Space (South Africa)

    Taylor, JRN

    1993-09-01

    Full Text Available An investigation into factors influencing beta-amylase activity in sorghum malt confirmed that ungerminated sorghum grain exhibited essentially no beta-amylase activity. Malted sorghum had beta-amylase activity less than 25% of the level in barley...

  11. Human cytomegalovirus IE2 protein interacts with transcription activating factors

    Institute of Scientific and Technical Information of China (English)

    XU; Jinping(徐进平); YE; Linbai(叶林柏)

    2002-01-01

    The human cytomegalovirus (HCMV) IE86 Cdna was cloned into Pgex-2T and fusion protein GST-IE86 was expressed in E. Coli. SDS-PAGE and Western blot assay indicated that fusion protein GST-IE86 with molecular weight of 92 ku is soluble in the supernatant of cell lysate. Protein GST and fusion protein GST-IE86 were purified by affinity chromatography. The technology of co-separation and specific affinity chromatography was used to study the interactions of HCMV IE86 protein with some transcriptional regulatory proteins and transcriptional factors. The results indicated that IE86 interacts separately with transcriptional factor TFIIB and promoter DNA binding transcription trans-activating factors SP1, AP1 and AP2 to form a heterogenous protein complex. These transcriptional trans-activating factors, transcriptional factor and IE86 protein were adsorbed and retained in the affinity chromatography simultaneously. But IE86 protein could not interact with NF-Кb, suggesting that the function of IE86 protein that can interact with transcriptional factor and transcriptional trans-activating factors has no relevance to protein glycosylation. IE86 protein probably has two domains responsible for binding transcriptional trans-activating regulatory proteins and transcriptional factors respectively, thus activating the transcription of many genes. The interactions accelerated the assembly of the transcriptional initiation complexes.

  12. [Factors influencing research activity of Andalusian nurses and improvement strategies].

    Science.gov (United States)

    López Alonso, Sergio R; Gálvez González, María; Amezcua, Manuel

    2013-04-01

    To identify factors influencing research activity of Andalusian nurses and to find improvement strategies. Qualitative research using SWOT analysis (weaknesses, threats, strengths, opportunities). Nurses were selected deliberately in eight groups according to predetermined criteria. Analysis included categorization and relationship of factors and strategies. 81 participants were included in groups of 7-12 range. 45 categories were identified with 212 factors: 12 weaknesses (50 factors), 10 strengths (44 factors), 12 threats (68 factors) and 11 opportunities (50 factors). In addition, 32 categories were identified with 53 strategies: 14 categories of W-T strategies (42 strategies), 3 categories of S-T strategies (11 strategies), 5 categories of W-O strategies (13 strategies) and 10 categories of S-O strategies (41 strategies). Nurses identified numerous factors, mainly threats. The strategies are focused on W-T but they also suggest many but weak 5-0 strategies due to the low potential of the opportunities and strengths perceived.

  13. Crystallographic B factor of critical residues at enzyme active site

    Institute of Scientific and Technical Information of China (English)

    张海龙; 宋时英; 林政炯

    1999-01-01

    Thirty-seven sets of crystallographic enzyme data were selected from Protein Data Bank (PDB, 1995). The average temperature factors (B) of the critical residues at the active site and the whole molecule of those enzymes were calculated respectively. The statistical results showed that the critical residues at the active site of most of the enzymes had lower B factors than did the whole molecules, indicating that in the crystalline state the critical residues at the active site of the natural enzymes possess more stable conformation than do the whole molecules. The flexibility of the active site during the unfolding by denaturing was also discussed.

  14. Nutrition, Physical Activity, and Obesity - Behavioral Risk Factor Surveillance System

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset includes data on adult's diet, physical activity, and weight status from Behavioral Risk Factor Surveillance System. This data is used for DNPAO's Data,...

  15. Quinic acid is a biologically active component of the Uncaria tomentosa extract C-Med 100.

    Science.gov (United States)

    Akesson, Christina; Lindgren, Hanna; Pero, Ronald W; Leanderson, Tomas; Ivars, Fredrik

    2005-01-01

    We have previously reported that the C-Med 100 extract of the plant Uncaria tomentosa induces prolonged lymphocyte half life and hence increased spleen cell number in mice receiving the extract in their drinking water. Further, the extract induces cell proliferation arrest and inhibits activation of the transcriptional regulator nuclear factor kappaB (NF-kappaB) in vitro. We now report that mice exposed to quinic acid (QA), a component of this extract, had significantly increased number of spleen cells, thus recapitulating the in vivo biological effect of C-Med 100 exposure. Commercially supplied QA (H(+) form) did not, however, inhibit cell proliferation in vitro, while the ammonia-treated QA (QAA) was a potent inhibitor. Both QA and QAA inhibited NF-kappaB activity in exposed cells at similar concentrations. Thus, our present data identify QA as a candidate component for both in vivo and in vitro biological effects of the C-Med 100 extract.

  16. Expression of protooncogenes during lymphocyte activation by growth factors.

    Science.gov (United States)

    Bulanova, E G; Budagyan, V M; Yarilin, A A; Mazurenko, N N

    1997-09-01

    Effects of growth factors of non-immune origin including somatotropin (ST) and platelet-derived growth factor (PDGF) on the expression of the proteins encoded by c-fos, c-myc, c-fun, and c-ets family protooncogenes were studied for the first time. The dynamics of the oncoprotein expression in activated CD(3+)-lymphocytes was investigated by immunoblotting. The accumulation of the Fos and Myc proteins was enhanced in T-lymphocytes treated with ST, PDGF, or phytohemagglutinin; the accumulation was maximum at 30-60 min and decreased in 2 h; the data indicate that the oncoproteins participate in the early lymphocyte activation by various growth factors. The Jun protein appears only in 3 h after the onset of lymphocyte activation; this suggests independent participation of Fos in the early stages of lymphocyte activation prior to the appearance of Jun, preceding the joint action of Fos and Jun within the AP-1 transcription complex. The products of the c-ets family are differentially activated by the studied growth factors. Resting lymphocytes actively accumulate the Ets-1 protein; ST and PDGF activation decreases Ets-1 expression in 2 h. The Ets-2 protein is not detected in resting cells and PDGF-activated lymphocytes, whereas lymphocyte activation by ST is associated with accumulation of Ets-2. The data suggest that the product of the c-ets-1 gene is more important in the regulation of resting cells and the product of the c-ets-2 gene is important during activation of lymphocytes by ST. The results indicate that activation of lymphocytes with growth factors of non-immune origin is mediated by several signal transduction pathways.

  17. Physical Activity : The interplay between individual and neighbourhood factors

    NARCIS (Netherlands)

    M.A. Beenackers (Marielle)

    2013-01-01

    textabstractPhysical inactivity is among the most important and prevalent risk factors of many major diseases. Although the health benefits of regular exercise and a physically active lifestyle are well known, many people are still not active. Understanding why some population groups are physically

  18. Poxvirus host range protein CP77 contains an F-box-like domain that is necessary to suppress NF-kappaB activation by tumor necrosis factor alpha but is independent of its host range function.

    Science.gov (United States)

    Chang, Shu-Jung; Hsiao, Jye-Chian; Sonnberg, Stephanie; Chiang, Cheng-Ting; Yang, Min-Hsiang; Tzou, Der-Lii; Mercer, Andrew A; Chang, Wen

    2009-05-01

    Tumor necrosis factor alpha (TNF-alpha) activates the nuclear factor kappaB (NF-kappaB) signaling pathway that regulates expression of many cellular factors playing important roles in innate immune responses and inflammation in infected hosts. Poxviruses employ many strategies to inhibit NF-kappaB activation in cells. In this report, we describe a poxvirus host range protein, CP77, which blocked NF-kappaB activation by TNF-alpha. Immunofluorescence analyses revealed that nuclear translocation of NF-kappaB subunit p65 protein in TNF-alpha-treated HeLa cells was blocked by CP77. CP77 did so without blocking IkappaBalpha phosphorylation, suggesting that upstream kinase activation was not affected by CP77. Using GST pull-down, we showed that CP77 bound to the NF-kappaB subunit p65 through the N-terminal six-ankyrin-repeat region in vitro. CP77 also bound to Cullin-1 and Skp1 of the SCF complex through a C-terminal 13-amino-acid F-box-like sequence. Both regions of CP77 are required to block NF-kappaB activation. We thus propose a model in which poxvirus CP77 suppresses NF-kappaB activation by two interactions: the C-terminal F-box of CP77 binding to the SCF complex and the N-terminal six ankyrins binding to the NF-kappaB subunit p65. In this way, CP77 attenuates innate immune response signaling in cells. Finally, we expressed CP77 or a CP77 F-box deletion protein from a vaccinia virus host range mutant (VV-hr-GFP) and showed that either protein was able to rescue the host range defect, illustrating that the F-box region, which is important for NF-kappaB modulation and binding to SCF complex, is not required for CP77's host range function. Consistently, knocking down the protein level of NF-kappaB did not relieve the growth restriction of VV-hr-GFP in HeLa cells.

  19. Potential Role of Activating Transcription Factor 5 during Osteogenesis

    Directory of Open Access Journals (Sweden)

    Luisa Vicari

    2016-01-01

    Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  20. MOTIVATIONAL FACTORS FOR PHYSICAL ACTIVITY IN THE ELDERS

    Directory of Open Access Journals (Sweden)

    J. Parreira

    2015-04-01

    Full Text Available Nowadays the elderly population is well aware of the benefits of the practice of physical activity, which leads to an increasing demand for specialized physical activity programs in urban centers or recreational self-practice. However, people easily quit those programs or recreational self-practice and return to a sedentary lifestyle. A key factor to avoid this quittance is to keep them motivated to practice and stay in the programs.Objectives: This study aims to understand the motivational factors that lead older people to physical activity in order to improve existing programs so to better meet the needs of this population.

  1. Activated protein C resistance testing for factor V Leiden.

    Science.gov (United States)

    Kadauke, Stephan; Khor, Bernard; Van Cott, Elizabeth M

    2014-12-01

    Activated protein C resistance assays can detect factor V Leiden with high accuracy, depending on the method used. Factor Xa inhibitors such as rivaroxaban and direct thrombin inhibitors including dabigatran, argatroban, and bivalirudin can cause falsely normal results. Lupus anticoagulants can cause incorrect results in most current assays. Assays that include dilution into factor V-deficient plasma are needed to avoid interference from factor deficiencies or elevations, which can arise from a wide variety of conditions such as warfarin, liver dysfunction, or pregnancy. The pros and cons of the currently available assays are discussed. © 2014 Wiley Periodicals, Inc.

  2. Comparison of automated von Willebrand factor activity assays

    DEFF Research Database (Denmark)

    Timm, Annette; Hillarp, Andreas; Philips, Malou

    2015-01-01

    activity/antigen ratios in samples classified as having VWD (activity classification power might interfere with the interpretation......INTRODUCTION: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Measurement of von Willebrand factor (VWF) activity in plasma is often based on platelet agglutination stimulated by the ristocetin cofactor activity. Novel assays, based on latex beads with recombinant...... glycoprotein Ib instead of platelets, have recently been developed but it is unclear whether these can improve the diagnostic capability for VWD. AIM: To compare four automated VWF activity methods in a mixed population of patients referred for evaluation of bleeding tendency. METHODS: The analytical...

  3. Comparison of kaolin and tissue factor activated thromboelastography in haemophilia.

    Science.gov (United States)

    Young, G; Zhang, R; Miller, R; Yassin, D; Nugent, D J

    2010-05-01

    A limitation of bypassing agent therapy for haemophilia patients with inhibitors is the absence of a laboratory assay, which predicts the clinical response to treatment. Recent investigations have demonstrated the potential for thromboelastography to assess the effects of bypassing agent therapy in this patient population. While tissue factor activation has been used in several prior studies, a recent multicentre study failed to demonstrate an expected concentration-response effect of rFVIIa and called into question the tissue factor activation methods that have been employed. A comparison of kaolin to two concentrations of tissue factor as the activation method for thromboelastography was investigated in patients with haemophilia. We performed kaolin and tissue factor activated thromboelastography on blood from inhibitor and non-inhibitor patients with and without addition of rFVIIa and rFVIII. The results demonstrate that kaolin leads to a longer R, K and angle than the higher dilution of tissue factor (1:17 000) at baseline (no factor) and after addition of rFVIIa for both the inhibitor and non-inhibitor patients. Kaolin led to a longer R and K in comparison to a low dilution of tissue factor (1:42 000) following the addition of rFVIIa in the inhibitor patients. The longer R and K allows for better discrimination of the effects of rFVIIa thus making kaolin the most sensitive activation method in this setting. Thus kaolin activated thromboelastography should be considered an effective, perhaps the most effective, activator when utilizing thromboelastography to assess the effects of rFVIIa in haemophilia patients with inhibitors.

  4. Enhanced osteoclastogenesis by mitochondrial retrograde signaling through transcriptional activation of the cathepsin K gene.

    Science.gov (United States)

    Guha, Manti; Srinivasan, Satish; Koenigstein, Alexander; Zaidi, Mone; Avadhani, Narayan G

    2016-01-01

    Mitochondrial dysfunction has emerged as an important factor in wide ranging human pathologies. We have previously defined a retrograde signaling pathway that originates from dysfunctional mitochondria (Mt-RS) and causes a global nuclear transcriptional reprograming as its end point. Mitochondrial dysfunction causing disruption of mitochondrial membrane potential and consequent increase in cytosolic calcium [Ca(2) ](c) activates calcineurin and the transcription factors NF-κB, NFAT, CREB, and C/EBPδ. In macrophages, this signaling complements receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastic differentiation. Here, we show that the Mt-RS activated transcriptional coactivator heterogeneous ribonucleoprotein A2 (hnRNP A2) is induced by hypoxia in murine macrophages. We demonstrate that the cathepsin K gene (Ctsk), one of the key genes upregulated during osteoclast differentiation, is transcriptionally activated by Mt-RS factors. HnRNP A2 acts as a coactivator with nuclear transcription factors, cRel, and C/EBPδ for Ctsk promoter activation under hypoxic conditions. Notably, our study shows that hypoxia-induced activation of the stress target factors mediates effects similar to that of RANKL with regard to Ctsk activation. We therefore suggest that mitochondrial dysfunction and activation of Mt-RS, induced by various pathophysiologic conditions, is a potential risk factor for osteoclastogenesis and bone loss.

  5. Enhanced osteoclastogenesis by mitochondrial retrograde signaling through transcriptional activation of the cathepsin K gene

    Science.gov (United States)

    Guha, Manti; Srinivasan, Satish; Koenigstein, Alexander; Zaidi, Mone; Avadhani, Narayan G.

    2015-01-01

    Mitochondrial dysfunction has emerged as an important factor in wide ranging human pathologies. We have previously defined a retrograde signaling pathway that originates from dysfunctional mitochondria (Mt-RS) and causes a global nuclear transcriptional reprograming as its endpoint. Mitochondrial dysfunction causing disruption of mitochondrial membrane potential and consequent increase in cytosolic calcium [Ca2](c) activates calcineurin and the transcription factors NF-κB, NFAT, CREB, and C/EBPδ. In macrophages this signaling complements receptor activator of nuclear factor kappa-B ligand (RANKL)–induced osteoclastic differentiation. Here, we show that the Mt-RS activated transcriptional coactivator heterogeneous ribonucleoprotein A2 (hnRNP A2) is induced by hypoxia in murine macrophages. We demonstrate that the cathepsin K gene (Cstk), one of the key genes upregulated during osteoclast differentiation, is transcriptionally activated by Mt-RS factors. HnRNP A2 acts as a coactivator with nuclear transcription factors, cRel, and C/EBPδ for Cstk promoter activation under hypoxic conditions. Notably, our study shows that hypoxia-induced activation of the stress target factors mediates effects similar to that of RANKL with regard to Cstk activation. We therefore suggest that mitochondrial dysfunction and activation of Mt-RS, induced by various pathophysiologic conditions, is a potential risk factor for osteoclastogenesis and bone loss. PMID:25800988

  6. Activity of recombinant factor VIIa under different conditions in vitro

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, Jørgen

    2008-01-01

    , but no effects on clotting time indicating that haemodilution does not affect clot formation, but the clot formed at high haemodilution may not be so firm. In conclusion, the activity of recombinant activated factor VII was affected in vitro by pH, temperature, and haemodilution. Additional studies are necessary...... investigated the in-vitro effects of pH, temperature, and haemodilution on the activity of recombinant activated factor VII. Samples from eight healthy volunteers were spiked with recombinant activated factor VII (final concentration 1.7 microg/ml) and adjusted to pH 6.0, 6.5, 7.0, and 7.4 or analysed at 30...... activity in plasma. Significant effects of pH were observed for clotting time, clot formation time, maximum clot firmness, and factor VII coagulant activity in the direction of longer clot formation times and less firm clots with decreasing pH. Temperature had significant effects on clotting time, clot...

  7. The effects of high fat, low carbohydrate and low fat, high carbohydrate diets on tumor necrosis factor superfamily proteins and proinflammatory cytokines in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Mahshid Sirjani

    2014-08-01

    Full Text Available There has been considerable inconsistency regarding the potential relationship between dyslipidemia and bone metabolism. The inflammatory stimulation through the receptor activator of the nuclear factor kappa-B ligand (RANKL/ receptor activator of the nuclear factor kappa-B (RANK/ osteoprotegerin (OPG pathway could be the infrastructural mechanism for hypercholesterolemia-induced bone loss.In this study, we investigated the effect of dyslipidemia on RANKL and OPG alongside with pro-inflammatory cytokines. Thirty male C57Bl/6 mice (4 weeks old were randomized to two purified diet groups (15 animals in each group, high fat, low carbohydrate diet (HFLCD and its matched low fat, high carbohydrate diet (LFHCD. After 12 weeks of feeding in standard situations, the plasma concentration of lipid profile, interleukin (IL 1Beta, IL-6, tumor necrosis factor-alpha (TNF-α and RANKL, OPG, and RANKL: OPG ratio were measured.In the present study, although the body weight significantly increased during 12 weeks in HFLCD and LFHCD groups, there were no significant differences in food intake, food efficiency ratio and weight gain between the two groups. The LFHCD group had significantly higher median RANKL and RANKL/OPG ratio. There was no significant difference in plasma IL-1β, IL-6 and TNF-α concentration between LFHCD and HFLCD groups.These unexpected findings from LFHCD, that seem to be as a result of its higher carbohydrate proportion in comparison to HFLCD, implicate dietary carbohydrate rather than dietary fat as a more significant nutritional factor contributing to change in RANKL level and RANKL: OPG ratio.

  8. Tissue factor activates allosteric networks in factor VIIa through structural and dynamic changes

    DEFF Research Database (Denmark)

    Madsen, Jesper Jonasson; Persson, E.; Olsen, O. H.

    2015-01-01

    Background: Tissue factor (TF) promotes colocalization of enzyme (factorVIIa) and substrate (FX or FIX), and stabilizes the active conformation of FVIIa. Details on how TF induces structural and dynamic changes in the catalytic domain of FVIIa to enhance its efficiency remain elusive. Objective...

  9. Heighten the Study on Factor Seven Activating Protease

    Institute of Scientific and Technical Information of China (English)

    贺石林; 陈方平; 张广森; 文志斌

    2008-01-01

    @@ Recent studies have showed that factor seven activating protease (FSAP) is a novel serine protease in human plasma. Immunoreactivity for FSAP has been observed in vascular endothelial cells,epithelial cells and macrophages but FSAP-specific mRNA expression only exists in the former two cells. FSAP has three epidermal growth factor (EGF) domains,a kringle domain and a serine protease domain.

  10. Physical activity and associated factors among students attending evening classes

    Directory of Open Access Journals (Sweden)

    Fabio Luis Ceschini

    2015-03-01

    Full Text Available The aim of this study was to describe the physical activity level and associated factors among students attending evening classes in public and private schools in a region of the city of São Paulo. The sample was composed of 1,844 adolescents of both sexes aged 15-20 years. Three public and private schools in the city of São Paulo were visited. Daily physical activity level was assessed through International Physical Activity Questionnaire that classifies physical activity level. Physical activity level was divided into insufficiently active (when subject reported less than 300 minutes of moderate to vigorous physical activities per week and physically active (when subject reported more than 300 minutes of moderate to vigorous physical activities per week. Information related to risk behavior such as smoking and alcohol consumption was collected. Data were analyzed using logistic regression with three levels of data input and p<.05 as significance level. The prevalence of physically active adolescents was 36.1%. Most active subjects were: A younger boys with low socioeconomic levels; B adolescents from private schools; C adolescents that do not smoke or drink alcoholic beverages; D those who do not attend formal exercise program; E those who go to school to perform physical activities on weekends. Adolescents attending evening classes tended to be insufficiently active. We believe that school structure, working hours, and distance from home and workplace to school and risk factor should explain these data. Intervention programs could significantly contribute to increase the physical activity level among adolescents.

  11. Psychosocial factors associated with increased physical activity in insufficiently active adults with arthritis.

    Science.gov (United States)

    Peeters, G M E E Geeske; Brown, Wendy J; Burton, Nicola W

    2015-09-01

    Although physical activity can potentially reduce symptoms of arthritis, 50% of people with arthritis are insufficiently active. The aim was to identify psychosocial factors associated with increased physical activity in mid-age adults with arthritis who did not meet recommended physical activity levels. Longitudinal cohort study. Data were from 692 insufficiently active men and women (mean age 55 ± 6.6 years) with arthritis, who answered mailed surveys in 2007 and 2009 in the HABITAT study. Increased physical activity was defined as a change of ≥ 200 MET min/week in walking, moderate and vigorous activities from 2007 to 2009. Scale scores were used to measure psychosocial factors including intention, experiences, attitudes, efficacy, barriers, motivation, social support, and health professional advice. Associations between (1) 2007 psychosocial factors and (2) 2007-2009 improvement (≥ +1 standard deviation) in psychosocial factors and increased physical activity were examined with logistic regression models. Results were adjusted for education, body mass index, and self-rated health. Between 2007 and 2009, 296 participants (42.8%) increased their physical activity. Engagement, mastery and physical activity intention in 2007 were associated with this increase in physical activity (engagement OR = 1.11, 99% confidence interval (CI) = 1.05-1.17; mastery OR = 1.12, 99%CI = 1.02-1.22; physical activity intention OR = 1.29, 99%CI = 1.06-1.56). Improved scores for encouragement (OR = 2.07, CI = 1.07-4.01) and self-efficacy (OR =2 .27, CI = 1.30-3.97) were also significantly associated with increased physical activity. Positive physical activity experiences and intentions were predictors of increased physical activity among people with arthritis. Improved physical activity confidence and social support were associated with increased physical activity. It is important to consider these psychosocial factors when planning physical activity interventions for people with

  12. Factor H-related proteins determine complement-activating surfaces.

    Science.gov (United States)

    Józsi, Mihály; Tortajada, Agustin; Uzonyi, Barbara; Goicoechea de Jorge, Elena; Rodríguez de Córdoba, Santiago

    2015-06-01

    Complement factor H-related proteins (FHRs) are strongly associated with different diseases involving complement dysregulation, which suggests a major role for these proteins regulating complement activation. Because FHRs are evolutionarily and structurally related to complement inhibitor factor H (FH), the initial assumption was that the FHRs are also negative complement regulators. Whereas weak complement inhibiting activities were originally reported for these molecules, recent developments indicate that FHRs may enhance complement activation, with important implications for the role of these proteins in health and disease. We review these findings here, and propose that FHRs represent a complex set of surface recognition molecules that, by competing with FH, provide improved discrimination of self and non-self surfaces and play a central role in determining appropriate activation of the complement pathway.

  13. Factors Associated with Early Platelet Activation in Obese Children

    Science.gov (United States)

    García, Anel Gómez; Núñez, Guillermina García; Sandoval, Martha Eva Viveros; Castellanos, Sergio Gutierrez; Aguilar, Cleto Alvarez

    2014-01-01

    Objective To investigate the factors associated with platelet activation in obese children. Design Cross-sectional study. Setting Department of Pediatrics of Regional Hospital N∘ 1 of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. Participants 79 obese and 64 non-obese children between the ages of 5 and 10 years. Main Outcomes Measures Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-obese children (percentile <85), % body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-1), lipid profile, and glucose. Results Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (β:0.381; t:4.665; P=0.0001), vWF (β:0.211; t:2.926; P=0.004), UA (β:0.166; t:2.146; P=0.034), and HDL (β:−0.215; t:−2.819; P=0.006). Conclusions Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults. PMID:24415745

  14. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Skouby, Sven O; Kluft, Cornelis

    2011-01-01

    Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... alloenzyme with reduced pro-fibrinolytic activity. Presently, we address whether OC use and OC formulation affect FSAP measures in human blood. Healthy women (n=588) were allocated to six cycles of OCs with estrogen contents of 20µg (n=158), 30µg (n=284), 35µg (n=79) or 50µg (n=67) combined with various...... progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P=0.001). OC use increased FSAP antigen by 25% and FSAP activity...

  15. Physical Activity in Adolescents following Treatment for Cancer: Influencing Factors.

    Science.gov (United States)

    Wright, Marilyn; Bryans, Angie; Gray, Kaylin; Skinner, Leah; Verhoeve, Amanda

    2013-01-01

    The purpose of this study was to examine physical activity levels and influencing individual and environmental factors in a group of adolescent survivors of cancer and a comparison group. Methods. The study was conducted using a "mixed methods" design. Quantitative data was collected from 48 adolescent survivors of cancer and 48 comparison adolescents using the Godin Leisure-Time Exercise Questionnaire, the Fatigue Scale-Adolescents, and the Amherst Health and Activity Study-Student Survey. Qualitative data was collected in individual semistructured interviews. Results. Reported leisure-time physical activity total scores were not significantly different between groups. Physical activity levels were positively correlated with adult social support factors in the group of adolescent survivors of cancer, but not in the comparison group. Time was the primary barrier to physical activity in both groups. Fatigue scores were higher for the comparison but were not associated with physical activity levels in either group. The qualitative data further supported these findings. Conclusions. Barriers to physical activity were common between adolescent survivors of cancer and a comparative group. Increased knowledge of the motivators and barriers to physical activity may help health care providers and families provide more effective health promotion strategies to adolescent survivors of pediatric cancer.

  16. Physical Activity in Adolescents following Treatment for Cancer: Influencing Factors

    Directory of Open Access Journals (Sweden)

    Marilyn Wright

    2013-01-01

    Full Text Available The purpose of this study was to examine physical activity levels and influencing individual and environmental factors in a group of adolescent survivors of cancer and a comparison group. Methods. The study was conducted using a “mixed methods” design. Quantitative data was collected from 48 adolescent survivors of cancer and 48 comparison adolescents using the Godin Leisure-Time Exercise Questionnaire, the Fatigue Scale—Adolescents, and the Amherst Health and Activity Study—Student Survey. Qualitative data was collected in individual semistructured interviews. Results. Reported leisure-time physical activity total scores were not significantly different between groups. Physical activity levels were positively correlated with adult social support factors in the group of adolescent survivors of cancer, but not in the comparison group. Time was the primary barrier to physical activity in both groups. Fatigue scores were higher for the comparison but were not associated with physical activity levels in either group. The qualitative data further supported these findings. Conclusions. Barriers to physical activity were common between adolescent survivors of cancer and a comparative group. Increased knowledge of the motivators and barriers to physical activity may help health care providers and families provide more effective health promotion strategies to adolescent survivors of pediatric cancer.

  17. Factors determining physical activity of Ukrainian students

    Directory of Open Access Journals (Sweden)

    Barbara Bergier

    2014-09-01

    Full Text Available [b]Objective[/b]. Scientific reports provide information concerning an insufficient level of physical activity of societies. The objective of the study is recognition of the level of physical activity among Ukrainian students, and factors which condition this activity: gender, place of residence, self-reported physical fitness, and the BMI. [b]Methods[/b]. The study was conducted in 2013 among 2,125 Ukrainian students using a long version of the International Physical Activity Questionnaire (IPAQ, supplemented with data concerning the respondents’ physical development. [b]Results[/b]. The results of the study showed that the mean total physical activity of students was 3.560 MET, and its highest percentage pertained to the area of activity in sports – 1.124 MET. Significantly higher statistically physical activity was observed among males than females. In males, the highest activity was related to participation in sports classes, while in females – engagement in household chores. It was found that males, compared to females, were significantly more physically active in such areas as occupational activity (education and sports activity, whereas females showed higher activity performing household chores. According to the place of residence, inhabitants of medium-size towns and rural areas obtained the most favourable results in activity, while the inhabitants of large cities the poorest. Self-reported physical fitness was significantly correlated with the results in physical activity obtained by the students. No relationship was found between the BMI and the level of student’s physical activity. [b]Conclusion[/b]. Considering the very large population of respondents, the results obtained may be considered as an up-to-date pattern of physical activity among Ukrainian students.

  18. Elevated plasma phospholipase A2 and platelet-activating factor acetylhydrolase activity in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Yves Denizot

    2004-01-01

    Full Text Available This clinical study reports that blood levels of the pro-inflammatory mediator platelet-activating factor (PAF did not change in colorectal cancer patients. In contrast, plasma levels of two enzymatic activities, one implicated in PAF production (i.e. phospholipase A2 and one in PAF degradation (i.e. PAF acetylhydrolase activity were significantly elevated.

  19. Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

    DEFF Research Database (Denmark)

    Rand, Kasper Dyrberg; Jørgensen, Thomas; Olsen, Ole H;

    2006-01-01

    Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics...... tissue factor binding, FVIIa undergoes dramatic structural stabilization as indicated by decreased exchange rates localized throughout the protease domain and in distant parts of the light chain, spanning across 50A and revealing a concerted interplay between functional sites in FVIIa. The results...... of distinct molecular states, namely zymogen FVII, endoproteolytically cleaved FVIIa, TF-bound zymogen FVII, TF-bound FVIIa, and FVIIa in complex with an active site inhibitor. The hydrogen exchange kinetics of zymogen FVII and FVIIa are identical indicating highly similar solution structures. However, upon...

  20. Mercuric ion attenuates nuclear factor-kappaB activation and DNA binding in normal rat kidney epithelial cells: implications for mercury-induced nephrotoxicity.

    Science.gov (United States)

    Dieguez-Acuña, F J; Ellis, M E; Kushleika, J; Woods, J S

    2001-06-15

    Mercuric ion (Hg(2+)), one of the strongest thiol-binding agents known, mediates the toxicity associated with elemental, inorganic, and organic mercurial compounds. Studies of cellular events associated with Hg(2+) toxicity have focused largely on disruption of cell membranes and impairment of mitochondrial functions. In contrast, few studies have sought to define the specific molecular mechanisms through which Hg(2+) might affect toxicity via alteration of thiol-dependent signal transduction pathways that regulate cell proliferation and survival. Of particular interest in this regard is the effect of Hg(2+) on nuclear factor-kappaB (NF-kappaB), a pleiotropic transcriptional factor that is known to require reduced cysteine moieties at critical steps of activation and DNA binding. Here, we evaluated the effects of Hg(2+) on the expression of NF-kappaB in normal rat kidney epithelial (NRK52E) cells, a principal target of Hg(2+) toxicity. The lipopolysaccharide (LPS)-inducible form of NF-kappaB was readily detected in kidney cells and has been characterized as the p50p65 heterodimer. NF-kappaB-DNA binding was prevented in a dose-related manner by Hg(2+) (0-55 microM) in vitro when added to DNA binding reactions containing the nonthiol reducing agent Tris(2-carboxyethyl)phosphine hydrochloride (TCEP). Similarly, Hg(2+) at the same concentrations prevented DNA binding of a human recombinant wild-type p50p50 homodimer in binding reactions, and this effect was attenuated using a mutant form of the p50 protein containing a cys(62)-->ser(62) mutation. The inhibition of p50-DNA binding by Hg(2+) was reversible in a dose-related manner in vitro by competitive thiols DTT, GSH, and l-cysteine in binding reactions. In contrast, competitive thiols added to nuclear binding reactions were unable to reverse attenuation of LPS-mediated NF-kappaB-DNA binding affinity when cells were pretreated in vivo with Hg(2+) at concentrations as low as 2 microM prior to LPS administration

  1. Changes in CVD risk factors in the activity counseling trial

    Directory of Open Access Journals (Sweden)

    Meghan Baruth

    2011-01-01

    Full Text Available Meghan Baruth1, Sara Wilcox1, James F Sallis3, Abby C King4,5, Bess H Marcus6, Steven N Blair1,21Department of Exercise Science, 2Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Public Health Research Center, Columbia, SC, USA; 3Department of Psychology, San Diego State University, San Diego, CA, USA; 4Department of Health Research and Policy, 5Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; 6Behavioral and Social Sciences Section, Brown University Program in Public Health, Providence, RI, USAAbstract: Primary care facilities may be a natural setting for delivering interventions that focus on behaviors that improve cardiovascular disease (CVD risk factors. The purpose of this study was to examine the 24-month effects of the Activity Counseling Trial (ACT on CVD risk factors, to examine whether changes in CVD risk factors differed according to baseline risk factor status, and to examine whether changes in fitness were associated with changes in CVD risk factors. ACT was a 24-month multicenter randomized controlled trial to increase physical activity. Participants were 874 inactive men and women aged 35–74 years. Participants were randomly assigned to one of three arms that varied by level of counseling, intensity, and resource requirements. Because there were no significant differences in change over time between arms on any of the CVD risk factors examined, all arms were combined, and the effects of time, independent of arm, were examined separately for men and women. Time × Baseline risk factor status interactions examined whether changes in CVD risk factors differed according to baseline risk factor status. Significant improvements in total cholesterol, high-density lipoprotein cholesterol (HDL-C and low-density lipoprotein cholesterol, the ratio of total cholesterol to HDL-C, and triglycerides were seen in

  2. Factors Predicting Physical Activity Among Children With Special Needs

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    Shahram Yazdani, MD

    2013-07-01

    Full Text Available Introduction Obesity is especially prevalent among children with special needs. Both lack of physical activity and unhealthful eating are major contributing factors. The objective of our study was to investigate barriers to physical activity among these children. Methods We surveyed parents of the 171 children attending Vista Del Mar School in Los Angeles, a nonprofit school serving a socioeconomically diverse group of children with special needs from kindergarten through 12th grade. Parents were asked about their child’s and their own physical activity habits, barriers to their child’s exercise, and demographics. The response rate was 67%. Multivariate logistic regression was used to examine predictors of children being physically active at least 3 hours per week. Results Parents reported that 45% of the children were diagnosed with attention deficit hyperactivity disorder, 38% with autism, and 34% with learning disabilities; 47% of children and 56% of parents were physically active less than 3 hours per week. The top barriers to physical activity were reported as child’s lack of interest (43%, lack of developmentally appropriate programs (33%, too many behavioral problems (32%, and parents’ lack of time (29%. However, child’s lack of interest was the only parent-reported barrier independently associated with children’s physical activity. Meanwhile, children whose parents were physically active at least 3 hours per week were 4.2 times as likely to be physically active as children whose parents were less physically active (P = .01. Conclusion In this group of students with special needs, children’s physical activity was strongly associated with parental physical activity; parent-reported barriers may have had less direct effect. Further studies should examine the importance of parental physical activity among children with special needs.

  3. LPS-inducible factor(s) from activated macrophages mediates cytolysis of Naegleria fowleri amoebae

    Energy Technology Data Exchange (ETDEWEB)

    Cleary, S.F.; Marciano-Cabral, F.

    1986-03-01

    Soluble cytolytic factors of macrophage origin have previously been described with respect to their tumoricidal activity. The purpose of this study was to investigate the mechanism and possible factor(s) responsible for cytolysis of the amoeba Naegleria fowleri by activated peritoneal macrophages from B6C3F1 mice. Macrophages or conditioned medium (CM) from macrophage cultures were incubated with /sup 3/H-Uridine labeled amoebae. Percent specific release of label served as an index of cytolysis. Bacille Calmette-Guerin (BCG) and Corynebacterium parvum macrophages demonstrated significant cytolysis of amoebae at 24 h with an effector to target ratio of 10:1. Treatment of macrophages with inhibitors of RNA or protein synthesis blocked amoebicidal activity. Interposition of a 1 ..mu..m pore membrane between macrophages and amoebae inhibited killing. Inhibition in the presence of the membrane was overcome by stimulating the macrophages with LPS. CM from SPS-stimulated, but not unstimulated, cultures of activated macrophages was cytotoxic for amoebae. The activity was heat sensitive and was recovered from ammonium sulfate precipitation of the CM. Results indicate that amoebicidal activity is mediated by a protein(s) of macrophage origin induced by target cell contact or stimulation with LPS.

  4. Activating transcription factor 4 regulates osteoclast differentiation in mice

    Science.gov (United States)

    Cao, Huiling; Yu, Shibing; Yao, Zhi; Galson, Deborah L.; Jiang, Yu; Zhang, Xiaoyan; Fan, Jie; Lu, Binfeng; Guan, Youfei; Luo, Min; Lai, Yumei; Zhu, Yibei; Kurihara, Noriyoshi; Patrene, Kenneth; Roodman, G. David; Xiao, Guozhi

    2010-01-01

    Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4–/– bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4–/– BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity. PMID:20628199

  5. Activating transcription factor 4 regulates osteoclast differentiation in mice.

    Science.gov (United States)

    Cao, Huiling; Yu, Shibing; Yao, Zhi; Galson, Deborah L; Jiang, Yu; Zhang, Xiaoyan; Fan, Jie; Lu, Binfeng; Guan, Youfei; Luo, Min; Lai, Yumei; Zhu, Yibei; Kurihara, Noriyoshi; Patrene, Kenneth; Roodman, G David; Xiao, Guozhi

    2010-08-01

    Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4-/- bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4-/- BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity.

  6. Platelet-activating factor in liver injury: A relational scope

    Institute of Scientific and Technical Information of China (English)

    Nikolaos P Karidis; Gregory Kouraklis; Stamatios E Theocharis

    2006-01-01

    The hepatocyte, the main cellular component of the liver, exhibits variable susceptibility to different types of injury induced by endogenous or exogenous factors.Hepatocellular dysfunction or death and regeneration are dependent upon the complicated interactions between numerous biologically active molecules. Plateletactivating factor (PAF) seems to play a pivotal role as the key mediator of liver injury in the clinical and experimental setting, as implied by the beneficial effects of its receptor antagonists. A comprehensive up-todate overview of the specific functional and regulatory properties of PAF in conditions associated with liver injury is attempted in this review.

  7. Factors related to physical activity: a study of adolescents.

    Science.gov (United States)

    Vilhjalmsson, R; Thorlindsson, T

    1998-09-01

    Although the consequences of physical activity have been carefully documented, less is known about its correlates, particularly among children and youth. Based on a representative national survey of 1131 Icelandic adolescents, the study examined various physical, psychological, social and demographic factors related to physical activity. Male sex, significant others' involvement in physical activity (father, friend and older brother), sociability, perceived importance of sport and of health improvement and satisfaction with mandatory gym classes in school, were all related to more involvement, whereas hours of paid work and TV-viewing were related to less. Furthermore, the data suggested that the influence of friend's participation in physical activity depends on his or her emotional significance. Influential others appeared to affect males and females in the same way. The meaning of the results and their implications for future research are discussed.

  8. Factor VII activating protease. Single nucleotide polymorphisms light the way.

    Science.gov (United States)

    Kanse, S M; Etscheid, M

    2011-08-01

    Factor VII activating protease (FSAP) is a circulating serine protease with high homology to fibrinolytic enzymes. A role in the regulation of coagulation and fibrinolysis is suspected based on in vitro studies demonstrating activation of FVII or pro-urokinase plasminogen activator (uPA). However, considering the paucity of any studies in animal models or any correlative studies in humans the role of FSAP in haemostasis remains unclear. In relation to vascular remodeling processes or inflammation it has been convincingly shown that FSAP interacts with growth factors as well as protease activated receptors (PAR). Against this sparse background there are a plethora of studies which have investigated the linkage of single nucleotide polymorphisms (SNP) in the FSAP gene (HABP2) to various diseases. The G534E SNP of FSAP is associated with a low proteolytic activity due to an amino acid exchange in the protease domain. This and other SNPs have been linked to carotid stenosis, stroke as well as thrombosis in the elderly and plaque calcification. These SNP analyses indicate an important role for FSAP in the regulation of the haemostasis system as well as fibroproliferative inflammatory processes.

  9. Risk factors for glucose intolerance in active acromegaly

    Directory of Open Access Journals (Sweden)

    Kreze A.

    2001-01-01

    Full Text Available In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33% had diabetes mellitus and 2 (5%; 1-16% impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test. A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.

  10. TALE factors poise promoters for activation by Hox proteins.

    Science.gov (United States)

    Choe, Seong-Kyu; Ladam, Franck; Sagerström, Charles G

    2014-01-27

    Hox proteins form complexes with TALE cofactors from the Pbx and Prep/Meis families to control transcription, but it remains unclear how Hox:TALE complexes function. Examining a Hoxb1b:TALE complex that regulates zebrafish hoxb1a transcription, we find maternally deposited TALE proteins at the hoxb1a promoter already during blastula stages. These TALE factors recruit histone-modifying enzymes to promote an active chromatin profile at the hoxb1a promoter and also recruit RNA polymerase II (RNAPII) and P-TEFb. However, in the presence of TALE factors, RNAPII remains phosphorylated on serine 5 and hoxb1a transcription is inefficient. By gastrula stages, Hoxb1b binds together with TALE factors to the hoxb1a promoter. This triggers P-TEFb-mediated transitioning of RNAPII to the serine 2-phosphorylated form and efficient hoxb1a transcription. We conclude that TALE factors access promoters during early embryogenesis to poise them for activation but that Hox proteins are required to trigger efficient transcription.

  11. Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

    Science.gov (United States)

    Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

    1999-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

  12. Feedback activation of neurofibromin terminates growth factor-induced Ras activation

    OpenAIRE

    Hennig, Anne; Markwart, Robby; Wolff, Katharina; Schubert, Katja; Cui, Yan; Ian A Prior; Manuel A Esparza-Franco; Ladds, Graham; Rubio, Ignacio

    2016-01-01

    This is the final published version. It first appeared at http://biosignaling.biomedcentral.com/articles/10.1186/s12964-016-0128-z. Background Growth factors induce a characteristically short-lived Ras activation in cells emerging from quiescence. Extensive work has shown that transient as opposed to sustained Ras activation is critical for the induction of mitogenic programs. Mitogen-induced accumulation of active Ras-GTP results from increased nucleotide exchange driven by the nucleo...

  13. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.

    Science.gov (United States)

    Naranjo, José R; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C; Arrabal, María D; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-02-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD.

  14. Factors affecting perceived change in physical activity in pregnancy.

    Science.gov (United States)

    Merkx, Astrid; Ausems, Marlein; Budé, Luc; de Vries, Raymond; Nieuwenhuijze, Marianne J

    2017-08-01

    reduction of physical activity (PA) during pregnancy is common but undesirable, as it is associated with negative outcomes, including excessive gestational weight gain. Our objective was to explore changes in five types of activity that occurred during pregnancy and the behavioural determinants of the reported changes in PA. we performed a secondary analysis of a cross sectional survey that was constructed using the ASE-Model - an approach to identifying the factors that drive behaviour change that focuses on Attitude, Social influence, and self-Efficacy. 455 healthy pregnant women of all gestational ages, receiving prenatal care from midwifery practices in the Netherlands. more than half of our respondents reported a reduction in their PA during pregnancy. The largest reduction occurred in sports and brief rigorous activities, but other types of PA were reduced as well. Reduction of PA was more likely in women who considered themselves as active before pregnancy, women who experienced pregnancy-related barriers, women who were advised to reduce their PA, and multiparous women. Fewer than 5% increased their PA. Motivation to engage in PA was positively associated with enjoying PA. all pregnant women should be informed about the positive effects of staying active and should be encouraged to engage in, or to continue, moderately intensive activities like walking, biking or swimming. Our findings concerning the predictors of PA reduction can be used to develop an evidence-based intervention aimed at encouraging healthy PA during pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Modulation of topoisomerase activities by tumor necrosis factor.

    Science.gov (United States)

    Baloch, Z; Cohen, S; Fresa, K; Coffman, F D

    1995-01-01

    A number of chemotherapeutic agents which inhibit the DNA topoisomerases markedly potentiate cell death mediated by tumor necrosis factor, suggesting a role for these enzymes in the TNF cytotoxic mechanism. To investigate this possibility, topoisomerase I and II activities were assayed following TNF addition to murine L929 cells. Topoisomerase I and II activities increased within 15 min of TNF addition and returned to baseline levels within 1 and 2 hr, respectively. The increases in both topoisomerase activities were blocked by H-7 (but not H-8) and similar increases were seen following PMA addition. However, concentrations of H-7 which blocked the increased topoisomerase activities had no effect on TNF cytotoxicity nor on the enhancement of TNF cytotoxicity by topoisomerase inhibitors. Thus, in these cells topoisomerase activities are directly modified by TNF during the initial phases of a cytotoxic response. However, neither TNF cytotoxicity nor the enhancement of TNF cytotoxicity by topoisomerase inhibitors appears to require the TNF-mediated increases in topoisomerase activities.

  16. Time-activity relationships to VOC personal exposure factors

    Science.gov (United States)

    Edwards, Rufus D.; Schweizer, Christian; Llacqua, Vito; Lai, Hak Kan; Jantunen, Matti; Bayer-Oglesby, Lucy; Künzli, Nino

    Social and demographic factors have been found to play a significant role in differences between time-activity patterns of population subgroups. Since time-activity patterns largely influence personal exposure to compounds as individuals move across microenvironments, exposure subgroups within the population may be defined by factors that influence daily activity patterns. Socio-demographic and environmental factors that define time-activity subgroups also define quantifiable differences in VOC personal exposures to different sources and individual compounds in the Expolis study. Significant differences in exposures to traffic-related compounds ethylbenzene, m- and p-xylene and o-xylene were observed in relation to gender, number of children and living alone. Categorization of exposures further indicated time exposed to traffic at work and time in a car as important determinants. Increased exposures to decane, nonane and undecane were observed for males, housewives and self-employed. Categorization of exposures indicated exposure subgroups related to workshop use and living downtown. Higher exposures to 3-carene and α-pinene commonly found in household cleaning products and fragrances were associated with more children, while exposures to traffic compounds ethylbenzene, m- and p-xylene and o-xylene were reduced with more children. Considerable unexplained variation remained in categorization of exposures associated with home product use and fragrances, due to individual behavior and product choice. More targeted data collection methods in VOC exposure studies for these sources should be used. Living alone was associated with decreased exposures to 2-methyl-1-propanol and 1-butanol, and traffic-related compounds. Identification of these subgroups may help to reduce the large amount of unexplained variation in VOC exposure studies. Further they may help in assessing impacts of urban planning that result in changes in behavior of individuals, resulting in shifts in

  17. Factors Associated With Ambulatory Activity in De Novo Parkinson Disease.

    Science.gov (United States)

    Christiansen, Cory; Moore, Charity; Schenkman, Margaret; Kluger, Benzi; Kohrt, Wendy; Delitto, Anthony; Berman, Brian; Hall, Deborah; Josbeno, Deborah; Poon, Cynthia; Robichaud, Julie; Wellington, Toby; Jain, Samay; Comella, Cynthia; Corcos, Daniel; Melanson, Ed

    2017-04-01

    Objective ambulatory activity during daily living has not been characterized for people with Parkinson disease prior to initiation of dopaminergic medication. Our goal was to characterize ambulatory activity based on average daily step count and examine determinants of step count in nonexercising people with de novo Parkinson disease. We analyzed baseline data from a randomized controlled trial, which excluded people performing regular endurance exercise. Of 128 eligible participants (mean ± SD = 64.3 ± 8.6 years), 113 had complete accelerometer data, which were used to determine daily step count. Multiple linear regression was used to identify factors associated with average daily step count over 10 days. Candidate explanatory variable categories were (1) demographics/anthropometrics, (2) Parkinson disease characteristics, (3) motor symptom severity, (4) nonmotor and behavioral characteristics, (5) comorbidities, and (6) cardiorespiratory fitness. Average daily step count was 5362 ± 2890 steps per day. Five factors explained 24% of daily step count variability, with higher step count associated with higher cardiorespiratory fitness (10%), no fear/worry of falling (5%), lower motor severity examination score (4%), more recent time since Parkinson disease diagnosis (3%), and the presence of a cardiovascular condition (2%). Daily step count in nonexercising people recruited for this intervention trial with de novo Parkinson disease approached sedentary lifestyle levels. Further study is warranted for elucidating factors explaining ambulatory activity, particularly cardiorespiratory fitness, and fear/worry of falling. Clinicians should consider the costs and benefits of exercise and activity behavior interventions immediately after diagnosis of Parkinson disease to attenuate the health consequences of low daily step count.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A170).

  18. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Skouby, Sven O.; Kluft, Cornelis

    2011-01-01

    Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... alloenzyme with reduced pro-fibrinolytic activity. Presently, we address whether OC use and OC formulation affect FSAP measures in human blood. Healthy women (n=588) were allocated to six cycles of OCs with estrogen contents of 20μg (n=158), 30μg (n=284), 35μg (n=79) or 50μg (n=67) combined with various...... progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P≤0.001). OC use increased FSAP antigen by 25% and FSAP activity...

  19. Absence of in vitro Procoagulant Activity in Immunoglobulin Preparations due to Activated Coagulation Factors

    Science.gov (United States)

    Oviedo, Adriana E.; Bernardi, María E.; Guglielmone, Hugo A.; Vitali, María S.

    2015-01-01

    Summary Background Immunoglobulin (IG) products, including intravenous (IVIG) or subcutaneous (SCIG) immunoglobulins are considered safe and effective for medical therapy; however, a sudden and unexpected increase in thromboembolic events (TE) after administration of certain batches of IVIG products has been attributed to the presence of activated coagulation factors, mainly factor XIa. Our aims were to examine the presence of enduring procoagulant activity during the manufacturing process of IGs, with special focus on monitoring factor XIa, and to evaluate the presence of in vitro procoagulant activity attributed to coagulation factors in different lots of IVIG and SCIG. Methods Samples of different steps of IG purification, 19 lots of IVIG and 9 of SCIG were analyzed and compared with 1 commercial preparation of IVIG and 2 of SCIG, respectively. Factors II, VII, IX, XI and XIa and non-activated partial thromboplastin time (NAPTT) were assayed. Results The levels of factors II, VII, IX, X and XI were non-quantifiable once fraction II had been re-dissolved and in all analyzed lots of IVIG and SCIG. The level of factor XIa at that point was under the detection limits of the assay, and NAPTT yielded values greater than the control during the purification process. In SCIG, we detected higher concentrations of factor XIa in the commercial products, which reached values up to 5 times higher than the average amounts found in the 9 batches produced by UNC-Hemoderivados. Factor XIa in commercial IVIG reached levels slightly higher than those of the 19 batches produced by UNC-Hemoderivados. Conclusion IVIG and SCIG manufactured by UNC-Hemoderivados showed a lack of thrombogenic potential, as demonstrated not only by the laboratory data obtained in this study but also by the absence of any reports of TE registered by the post marketing pharmacovigilance department. PMID:26733772

  20. Differential activation of dendritic cells by nerve growth factor and brain-derived neurotrophic factor.

    Science.gov (United States)

    Noga, O; Peiser, M; Altenähr, M; Knieling, H; Wanner, R; Hanf, G; Grosse, R; Suttorp, N

    2007-11-01

    Neurotrophins are involved in inflammatory reactions influencing several cells in health and disease including allergy and asthma. Dendritic cells (DCs) play a major role in the induction of inflammatory processes with an increasing role in allergic diseases as well. The aim of this study was to investigate the influence of neurotrophins on DC function. Monocyte-derived dendritic cells were generated from allergic and non-allergic donors. Neurotrophin receptors were demonstrated by western blotting, flow cytometry and fluorescence microscopy. Activation of small GTPases was evaluated by pull-down assays. DCs were incubated with nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and supernatants were collected for measurement of IL-4, IL-6, IL-10, IL-12p70, TNF-alpha and TGF-beta. Receptor proteins were detectable by western blot, fluorescence activated cell sorting analysis and fluorescence microscopy. Signalling after neurotrophin stimulation occurred in a ligand-specific pattern. NGF led to decreased RhoA and increased Rac activation, while BDNF affected RhoA and Rac activity in a reciprocal fashion. Cells of allergics released a significantly increased amount of IL-6, while for healthy subjects a significantly higher amount of IL-10 was found. These data indicate that DCs are activated by the neurotrophins NGF and BDNF by different pathways in a receptor-dependant manner. These cells then may initiate inflammatory responses based on allergic sensitization releasing preferred cytokines inducing tolerance or a T-helper type 2 response.

  1. Restoring apoptosis in pancreatic cancer cells by targeting the nuclear factor-kappaB signaling pathway with the anti-epidermal growth factor antibody IMC-C225.

    Science.gov (United States)

    Sclabas, Guido M; Fujioka, Shuichi; Schmidt, Christian; Fan, Zhen; Evans, Douglas B; Chiao, Paul J

    2003-01-01

    We have previously demonstrated that RelA is constitutively activated in the majority of human pancreatic cancers and plays an important role in tumorigenesis and metastasis. The antiapoptotic gene bcl-xl is a downstream target of RelA, and regulation of bcl-xl transcription is mediated directly by the nuclear factor kappaB (NF-kappaB) binding sites present in the upstream promoter element of the bcl-xl gene. In this study we investigated the effects of inhibition of epidermal growth factor receptor (EGFR) signaling pathway with the anti-EGFR monoclonal antibody IMC-C225 on constitutive NF-kappaB activation and regulation of apoptosis-related genes in human pancreatic cancer cells. We found that activation of EGFR can be blocked with the anti-EGFR antibody IMC-C225 in the human pancreatic cancer cell line MDA Panc-28, leading to a marked decrease in constitutive NF-kappaB DNA binding activity. Our data also suggest that downregulation of NF-kappaB DNA binding activity by IMC-C225 leads to a decrease in bcl-xl and bfl-1 expression. Therefore, targeting the NF-kappaB signaling pathway with an anti-EGFR antibody may be one strategy to restore apoptosis in human pancreatic cancer cells, thereby enhancing the effect of chemotherapy and radiation therapy.

  2. [Activated protein C resistance and factor V Leiden: clinical interest].

    Science.gov (United States)

    Guermazi, S; Znazen, R

    2011-10-01

    Activated protein C resistance (APCR) is a coagulation abnormality often linked to FV Leiden mutation, a single nucleotide G1691A substitution resulting in arginine 506→glutamine missense factor V mutation. FV Leiden has a frequency of 20 to 30% in groups of patients with venous thrombosis while it is of 4 to 10% in normal subjects. FV Leiden is considered as a weak risk factor of thrombosis except in homozygote. FV Leiden is implicated in deep venous thrombosis occurrence. Duration of oral anticoagulant treatment is six months in patients developing a first venous thrombosis except in patients with combined defects or a clinical context suggesting a high risk of severe relapse. Detection of APCR by coagulation methods is often used in first intention with a high specificity if plasmas tested are diluted in factor V deficient plasma. Genotyping study is essential to establish the heterozygote or homozygote statute and certain teams perform it directly. Nevertheless, APCR not related to FV Leiden could be an independent thrombosis risk factor. APCR and FV Leiden are included in laboratory investigations of thrombophilic markers in patients less than 50 years with venous thrombosis. In arterial thrombosis, FV Leiden implication is weak or absent. FV Leiden increases the risk of thrombosis in other situations as in patients with cancer. An association with recurrent miscarriages and other vasculoplacental complications is also reported in many studies but the data concerning the efficacy of antithrombotic treatment to prevent recurrence are currently insufficient. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  3. The dust covering factor in active galactic nuclei

    CERN Document Server

    Stalevski, Marko; Ueda, Yoshihiro; Lira, Paulina; Fritz, Jacopo; Baes, Maarten

    2016-01-01

    The primary source of emission of active galactic nuclei (AGN), the accretion disk, is surrounded by an optically and geometrically thick dusty structure ("the so-called dusty torus"). The infrared radiation emitted by the dust is nothing but a reprocessed fraction of the accretion disk emission, so the ratio of the torus to the AGN luminosity ($L_{\\text{torus}}/L_{\\text{AGN}}$) should correspond to the fraction of the sky obscured by dust, i.e. the covering factor. We undertook a critical investigation of the $L_{\\text{torus}}/L_{\\text{AGN}}$ as the dust covering factor proxy. Using state-of-the-art 3D Monte Carlo radiative transfer code, we calculated a grid of SEDs emitted by the clumpy two-phase dusty structure. With this grid of SEDs, we studied the relation between $L_{\\text{torus}}/L_{\\text{AGN}}$ and the dust covering factor for different parameters of the torus. We found that in case of type 1 AGNs the torus anisotropy makes $L_{\\text{torus}}/L_{\\text{AGN}}$ underestimate low covering factors and ove...

  4. Factor VII activating protease (FSAP) promotes the proteolysis and inhibition of tissue factor pathway inhibitor (TFPI)

    Science.gov (United States)

    Kanse, Sandip M.; Declerck, Paul J.; Ruf, Wolfram; Broze, George; Etscheid, Michael

    2013-01-01

    Objectives Factor VII activating protease (FSAP) activates FVII as well as pro-urokinase and inhibits platelet-derived growth factor-BB, thus regulating haemostasis- and remodeling-associated processes in the vasculature. A genetic variant of FSAP (Marburg I polymorphism) results in low enzymatic activity and is associated with an enhanced risk for carotid stenosis and stroke. We postulate that there are additional substrates for FSAP that will help to explain its role in vascular biology and have searched for such a substrate. Results and Methods Using screening procedures to determine the influence of FSAP on various haemostasis-related processes on endothelial cells we discovered that FSAP inhibited tissue factor pathway inhibitor (TFPI), a major anti-coagulant secreted by these cells. Proteolytic degradation of TFPI by FSAP could also be demonstrated by Western blotting and the exact cleavage sites were determined by N-terminal sequencing. The Marburg I variant of FSAP had a diminished ability to inhibit TFPI. A monoclonal antibody to FSAP, that specifically inhibited FSAP binding to TFPI, reversed the inhibitory effect of FSAP on TFPI. Conclusions The identification of TFPI as a sensitive substrate for FSAP increases our understanding of its role in regulating haemostasis and proliferative remodeling events in the vasculature. PMID:22116096

  5. Enhanced imaging of DNA via active quality factor control

    Science.gov (United States)

    Humphris, A. D. L.; Round, A. N.; Miles, M. J.

    2001-10-01

    Adsorption processes at single molecule level are of fundamental importance for the understanding and development of biomaterials. Atomic force microscopy (AFM) has played a critical role in this field due to its high resolution and ability to image in a liquid environment. We present a method that improves the dynamic force sensitivity and the resolution of a conventional AFM. This is achieved via a positive feedback loop that enhances the effective quality factor of the cantilever in a liquid environment to values in excess of 300, compared to a nominal value of ˜1. This active quality factor enhancement has been used to image DNA and an increase in the height of the molecule observed.

  6. Nuclear factor Y regulates ancient budgerigar hepadnavirus core promoter activity.

    Science.gov (United States)

    Shen, Zhongliang; Liu, Yanfeng; Luo, Mengjun; Wang, Wei; Liu, Jing; Liu, Wei; Pan, Shaokun; Xie, Youhua

    2016-09-16

    Endogenous viral elements (EVE) in animal genomes are the fossil records of ancient viruses and provide invaluable information on the origin and evolution of extant viruses. Extant hepadnaviruses include avihepadnaviruses of birds and orthohepadnaviruses of mammals. The core promoter (Cp) of hepadnaviruses is vital for viral gene expression and replication. We previously identified in the budgerigar genome two EVEs that contain the full-length genome of an ancient budgerigar hepadnavirus (eBHBV1 and eBHBV2). Here, we found eBHBV1 Cp and eBHBV2 Cp were active in several human and chicken cell lines. A region from nt -85 to -11 in eBHBV1 Cp was critical for the promoter activity. Bioinformatic analysis revealed a putative binding site of nuclear factor Y (NF-Y), a ubiquitous transcription factor, at nt -64 to -50 in eBHBV1 Cp. The NF-Y core binding site (ATTGG, nt -58 to -54) was essential for eBHBV1 Cp activity. The same results were obtained with eBHBV2 Cp and duck hepatitis B virus Cp. The subunit A of NF-Y (NF-YA) was recruited via the NF-Y core binding site to eBHBV1 Cp and upregulated the promoter activity. Finally, the NF-Y core binding site is conserved in the Cps of all the extant avihepadnaviruses but not of orthohepadnaviruses. Interestingly, a putative and functionally important NF-Y core binding site is located at nt -21 to -17 in the Cp of human hepatitis B virus. In conclusion, our findings have pinpointed an evolutionary conserved and functionally critical NF-Y binding element in the Cps of avihepadnaviruses.

  7. Factor XI and contact activation as targets for antithrombotic therapy.

    Science.gov (United States)

    Gailani, D; Bane, C E; Gruber, A

    2015-08-01

    The most commonly used anticoagulants produce therapeutic antithrombotic effects either by inhibiting thrombin or factor Xa (FXa) or by lowering the plasma levels of the precursors of these key enzymes, prothrombin and FX. These drugs do not distinguish between thrombin generation contributing to thrombosis from thrombin generation required for hemostasis. Thus, anticoagulants increase bleeding risk, and many patients who would benefit from therapy go untreated because of comorbidities that place them at unacceptable risk for hemorrhage. Studies in animals demonstrate that components of the plasma contact activation system contribute to experimentally induced thrombosis, despite playing little or no role in hemostasis. Attention has focused on FXII, the zymogen of a protease (FXIIa) that initiates contact activation when blood is exposed to foreign surfaces, and FXI, the zymogen of the protease FXIa, which links contact activation to the thrombin generation mechanism. In the case of FXI, epidemiologic data indicate this protein contributes to stroke and venous thromboembolism, and perhaps myocardial infarction, in humans. A phase 2 trial showing that reduction of FXI may be more effective than low molecular weight heparin at preventing venous thrombosis during knee replacement surgery provides proof of concept for the premise that an antithrombotic effect can be uncoupled from an anticoagulant effect in humans by targeting components of contact activation. Here, we review data on the role of FXI and FXII in thrombosis and results of preclinical and human trials for therapies targeting these proteins.

  8. Role of PDI in regulating tissue factor: FVIIa activity.

    Science.gov (United States)

    Popescu, Narcis I; Lupu, Cristina; Lupu, Florea

    2010-04-01

    Cell exposed tissue factor (TF) is generally in a low procoagulant ("cryptic") state, and requires an activation step (decryption) to exhibit its full procoagulant potential. Recent data suggest that TF decryption may be regulated by the redox environment through the oxidoreductase activity of protein disulfide isomerase (PDI). In this article we review PDI contribution to different models of TF decryption, namely the disulfide switch model and the phosphatidylserine dynamics, and hypothesize on PDI contribution to TF self-association and association with lipid domains. Experimental evidence debate the disulfide switch model of TF decryption and its regulation by PDI. More recently we showed that PDI oxidoreductase activity regulates the phosphatidylserine equilibrium at the plasma membrane. Interestingly, PDI reductase activity could maintain TF in the reduced monomeric form, while also maintaining low exposure of PS, both states correlated with low procoagulant function. In contrast, PDI inhibition or oxidants may promote the adverse effects with a net increase in coagulation. The relative contribution of disulfide isomerization and PS exposure needs to be further analyzed to understand the redox control of TF procoagulant function. For the moment however TF regulation remains cryptic.

  9. Thioredoxin interacting protein inhibits hypoxia-inducible factor transcriptional activity

    Science.gov (United States)

    Farrell, Michael R; Rogers, Lynette K; Liu, Yusen; Welty, Stephen E; Tipple, Trent E

    2010-01-01

    Vascular endothelial growth factor (VEGF) is required for proper lung development and is transcriptionally regulated in alveolar epithelial cells by hypoxia inducible factor (HIF). Previous findings in a newborn mouse model of bronchopulmonary dysplasia (BPD) suggest that thioredoxin interacting protein (Txnip) is a novel regulator of VEGF expression. The present studies were designed to test the hypothesis that Txnip negatively regulates VEGF through effects on HIF-mediated gene expression. To test this hypothesis, we first examined the levels of VEGF and Txnip protein in the lungs of 1 day-old newborn and E19 embryos and detected a significant inverse correlation. To elucidate the mechanisms underlying this relationship, we studied the effects of Txnip overexpression on HIF-mediated transcription using murine lung epithelial (MLE-12) cells. Overexpression of Txnip inhibited HIF-mediated reporter activity in both hypoxia and room air. Suppression of HIF activity by Txnip appeared to be independent of the ability of Txnip to bind to thioredoxin. Thus, our studies support a model in which Txnip is a potentially critical regulator of HIF-mediated gene transcription in the murine lung. Alterations in Txnip expression could alter lung VEGF expression in prematurely born human infants and contribute to the development of BPD. PMID:20692333

  10. IDENTIFICATION OF CRITICAL SSCM ACTIVITIES THROUGH CONFIRMATORY FACTOR ANALYSIS

    Directory of Open Access Journals (Sweden)

    V. Narasimham

    2013-06-01

    Full Text Available As a developing country, economic and environmental performance has to be balanced in India. Green supply chain management (GSCM is emerging as an important proactive approach for Indian enterprises for improving environmental performance of processes and products in accordance with the requirements of environmental regulations. This study examines the consistency approaches by confirmatory factor analysis that determines the construct validity, convergent validity,construct reliability and internal consistency of the items of Sustainable supply chain management (SSCM requirements. This study examines the consistency approaches by Confirmatory factor analysis that determines the adoption and implementation of Sustainable supply chain management activities in small & medium scale industries. The requirements include Management commitment, customer coordination, sustainable design & production, green procurement and eco logistics for sustainable supply chains. This study suggested that the five factor model with eighteen items of the sustainable supply chain design had a good fit. Further, the study showed a valid and reliable measurement to identify critical items among the requirements of sustainable supply chains.

  11. Factors associated with Spanish older people's membership in political organizations: the role of active aging activities.

    Science.gov (United States)

    Serrat, Rodrigo; Villar, Feliciano; Celdrán, Montserrat

    2015-09-01

    This study explores older people's membership in political organizations by using data from the Survey on older people 2010, carried out by Spain's National Institute for older people and social services. The objectives were to describe the extent of this kind of participation among Spaniards aged 65 and over, and to analyze the factors that are associated with it. Results show that only slightly less than 7 % of the sample belonged to a political organization. To analyze the factors related to this membership, a set of models of multivariate analyses were run, including socioeconomic resources and participation in other types of active aging activity (participation in leisure, learning, and productive activities). Educational level, leisure activities, learning activities, and only volunteering in the case of productive activities were found to be associated with membership in political organizations. Results provide partial support for the socioeconomic resources model and suggest that engagement in leisure activities, learning activities, and volunteering might have an enhancing effect on membership in political organizations.

  12. Arabidopsis sigma factor binding proteins are activators of the WRKY33 transcription factor in plant defense.

    Science.gov (United States)

    Lai, Zhibing; Li, Ying; Wang, Fei; Cheng, Yuan; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

    2011-10-01

    Necrotrophic pathogens are important plant pathogens that cause many devastating plant diseases. Despite their impact, our understanding of the plant defense response to necrotrophic pathogens is limited. The WRKY33 transcription factor is important for plant resistance to necrotrophic pathogens; therefore, elucidation of its functions will enhance our understanding of plant immunity to necrotrophic pathogens. Here, we report the identification of two WRKY33-interacting proteins, nuclear-encoded SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2, which also interact with plastid-encoded plastid RNA polymerase SIGMA FACTOR1. Both SIB1 and SIB2 contain an N-terminal chloroplast targeting signal and a putative nuclear localization signal, suggesting that they are dual targeted. Bimolecular fluorescence complementation indicates that WRKY33 interacts with SIBs in the nucleus of plant cells. Both SIB1 and SIB2 contain a short VQ motif that is important for interaction with WRKY33. The two VQ motif-containing proteins recognize the C-terminal WRKY domain and stimulate the DNA binding activity of WRKY33. Like WRKY33, both SIB1 and SIB2 are rapidly and strongly induced by the necrotrophic pathogen Botrytis cinerea. Resistance to B. cinerea is compromised in the sib1 and sib2 mutants but enhanced in SIB1-overexpressing transgenic plants. These results suggest that dual-targeted SIB1 and SIB2 function as activators of WRKY33 in plant defense against necrotrophic pathogens.

  13. Risk factors of falls in community dwelling active elderly.

    Science.gov (United States)

    Tuunainen, Eeva; Rasku, Jyrki; Jäntti, Pirkko; Pyykkö, Ilmari

    2014-02-01

    To search for measures to describe and relate to accidental falls in community dwelling elderly. A EuroQol EQ-5D questionnaire based on a patient's otoneurological case history provided a general health related quality of life measure, a fall history for the last 3 months and force platform measures for 96 active elderly from a pensioner organization. On average, the elderly experienced 0.3 falls over the preceding three months. A fall was seen to cause a significant deterioration in the quality of life and vertigo and caused fear of falling. The postural instability correlated with falls. Vertigo was present among 42% and was most commonly characterized as episodic and rotatory in factorial analysis items relating to vertigo correlated to falls and balance complaints. Four factors were identified and three of these correlated with falls. Vestibular failure correlated to a fall occurring when a person was rising up; Movement intolerance correlated with falls due to slips and trips, and Near-syncope factor correlated to falls for other reasons. In posturography, the variable measuring critical time describing the memory based "closed loop" control of postural stability carried a risk for accidental fall with an odds ratio of 6. The variable measuring zero crossing velocity showed a high rate of velocity change around the neutral position of stance. Vertigo and poor postural stability were the major reasons for falls in the active elderly. In ageing, postural control is shifted towards open loop control (visual, proprioception, exteroception and vestibular) instead of closed loop control and is a factor that contributes to a fall. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Coagulation Factor Xa inhibits cancer cell migration via Protease-activated receptor-1 activation

    NARCIS (Netherlands)

    Borensztajn, Keren; Bijlsma, Maarten F.; Reitsma, Pieter H.; Peppelenbosch, Maikel R.; Spek, C. Arnold

    2009-01-01

    Cell migration is critically important in (patho) physiological processes. The metastatic potential of cancer cells partly depends on activation of the coagulation cascade. The aim of the present study was to determine whether coagulation factor X (FXa) can regulate the migration and invasion of can

  15. Associations between Socio-Motivational Factors, Physical Education Activity Levels and Physical Activity Behavior among Youth

    Science.gov (United States)

    Ning, Weihong; Gao, Zan; Lodewyk, Ken

    2012-01-01

    This study examined the relationships between established socio-motivational factors and children's physical activity levels daily and during physical education classes. A total of 307 middle school students (149 boys, 158 girls) from a suburban public school in the Southern United States participated in this study. Participants completed…

  16. Arenavirus nucleoproteins prevent activation of nuclear factor kappa B.

    Science.gov (United States)

    Rodrigo, W W Shanaka I; Ortiz-Riaño, Emilio; Pythoud, Christelle; Kunz, Stefan; de la Torre, Juan C; Martínez-Sobrido, Luis

    2012-08-01

    Arenaviruses include several causative agents of hemorrhagic fever (HF) disease in humans that are associated with high morbidity and significant mortality. Morbidity and lethality associated with HF arenaviruses are believed to involve the dysregulation of the host innate immune and inflammatory responses that leads to impaired development of protective and efficient immunity. The molecular mechanisms underlying this dysregulation are not completely understood, but it is suggested that viral infection leads to disruption of early host defenses and contributes to arenavirus pathogenesis in humans. We demonstrate in the accompanying paper that the prototype member in the family, lymphocytic choriomeningitis virus (LCMV), disables the host innate defense by interfering with type I interferon (IFN-I) production through inhibition of the interferon regulatory factor 3 (IRF3) activation pathway and that the viral nucleoprotein (NP) alone is responsible for this inhibitory effect (C. Pythoud, W. W. Rodrigo, G. Pasqual, S. Rothenberger, L. Martínez-Sobrido, J. C. de la Torre, and S. Kunz, J. Virol. 86:7728-7738, 2012). In this report, we show that LCMV-NP, as well as NPs encoded by representative members of both Old World (OW) and New World (NW) arenaviruses, also inhibits the nuclear translocation and transcriptional activity of the nuclear factor kappa B (NF-κB). Similar to the situation previously reported for IRF3, Tacaribe virus NP (TCRV-NP) does not inhibit NF-κB nuclear translocation and transcriptional activity to levels comparable to those seen with other members in the family. Altogether, our findings demonstrate that arenavirus infection inhibits NF-κB-dependent innate immune and inflammatory responses, possibly playing a key role in the pathogenesis and virulence of arenavirus.

  17. Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice.

    Science.gov (United States)

    Liang, Hai Po H; Kerschen, Edward J; Basu, Sreemanti; Hernandez, Irene; Zogg, Mark; Jia, Shuang; Hessner, Martin J; Toso, Raffaella; Rezaie, Alireza R; Fernández, José A; Camire, Rodney M; Ruf, Wolfram; Griffin, John H; Weiler, Hartmut

    2015-11-19

    The key effector molecule of the natural protein C pathway, activated protein C (aPC), exerts pleiotropic effects on coagulation, fibrinolysis, and inflammation. Coagulation-independent cell signaling by aPC appears to be the predominant mechanism underlying its highly reproducible therapeutic efficacy in most animal models of injury and infection. In this study, using a mouse model of Staphylococcus aureus sepsis, we demonstrate marked disease stage-specific effects of the anticoagulant and cell signaling functions of aPC. aPC resistance of factor (f)V due to the R506Q Leiden mutation protected against detrimental anticoagulant effects of aPC therapy but also abrogated the anti-inflammatory and mortality-reducing effects of the signaling-selective 5A-aPC variant that has minimal anticoagulant function. We found that procofactor V (cleaved by aPC at R506) and protein S were necessary cofactors for the aPC-mediated inhibition of inflammatory tissue-factor signaling. The anti-inflammatory cofactor function of fV involved the same structural features that govern its cofactor function for the anticoagulant effects of aPC, yet its anti-inflammatory activities did not involve proteolysis of activated coagulation factors Va and VIIIa. These findings reveal a novel biological function and mechanism of the protein C pathway in which protein S and the aPC-cleaved form of fV are cofactors for anti-inflammatory cell signaling by aPC in the context of endotoxemia and infection.

  18. Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Véronique Truffinet; Francois Labrousse; Yves Denizot

    2006-01-01

    AIM: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF (the PAF precursor),phospholipase A2 (PLA2, the enzymatic activity generating lyso-PAF), acetylhydrolase activity (AHA, the PAF degrading enzyme) and PAF receptor (PAF-R) transcripts in cirrhotic liver and hepatocellular carcinoma (HCC).METHODS: Twenty-nine patients with HCC were ehrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. LysoPAF was assessed after its chemical acetylation into PAF.AHA was determined by degradation of [3H]-PAF. PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR.RESULTS: Elevated amounts of PAF and PAF-R transcripts 1 (leukocyte-type) were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 (tissue-type) were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC.CONCLUSION: While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.

  19. Induction of xanthine oxidase activity, endoplasmic reticulum stress and caspase activation by sodium metabisulfite in rat liver and their attenuation by Ghrelin.

    Science.gov (United States)

    Ercan, Sevim; Kencebay, Ceren; Basaranlar, Goksun; Derin, Narin; Aslan, Mutay

    2015-02-01

    Sodium metabisulfite is used as a preservative in many food preparations but can oxidize to sulfite radicals initiating molecular oxidation. Ghrelin is a peptide hormone primarily produced in the stomach and has anti-inflammatory and anti-oxidant effects on gastrointestinal and cardiovascular systems. This study was performed to elucidate the effect of ghrelin on sulfite-induced endoplasmic reticulum (ER) stress and caspase activation in rat peripheral organs. Xanthine oxidase (XO), xanthine dehydrogenase (XDH) enzyme activities, ER stress markers [phosphorylated PKR-like ER kinase (pPERK); C/EBP-homologous protein (CHOP)], caspase-3, -8, -9 activities, nuclear factor kappa-B (NF-κB) levels were determined in liver, heart and kidney of rats treated with sodium metabisulfite and/or ghrelin for 5 weeks. Sodium metabisulfite treatment significantly elevated XO activity, induced expression of GRP78, CHOP and increased caspase-3, -8 and -9 activities in liver but had no significant effect in heart and kidney. Ghrelin treatment decreased XO activity to baseline levels and attenuated ER stress and caspase activation in liver tissue of sodium metabisulfite treated rats. In conclusion, metabolism of sodium metabisulfite in liver tissue increased XO activity, induced ER stress and caused caspase activation which was attenuated by ghrelin treatment. Ghrelin's hepatoprotective effect could be through modulation of XO activity.

  20. hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.

    Directory of Open Access Journals (Sweden)

    Shunsuke Ohnishi

    Full Text Available CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1-P5 of CD133 in human embryonic kidney (HEK 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α. Deletion and mutation analysis identified one of the two E-twenty six (ETS binding sites (EBSs in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.

  1. [Antifibrillatory activity of dipeptide antagonist of nerve growth factor].

    Science.gov (United States)

    Kryzhanovskiĭ, S A; Stoliarchuk, V N; Vititnova, M B; Tsorin, I B; Pekel'dina, E S; Gudasheva, T A

    2012-01-01

    In experiments on anesthetized rats were assessed antifibrillatoty action of dipeptide GK-1. This compound is the fragment of fourth loop of nerve growth factor (NGF) and manifests antagonistic activity in respect to TrkA receptor, that specified for NGF. It is shown that this compound is able to significantly increase the threshold of electrical fibrillation of the heart and its effectiveness is not inferior to the reference antiarrhythmics I and III class on Vaughan Williams classification. However, unlike the latter, antifibrillatory action of dipeptide GK-1 was delayed and realized within 40-60 minutes after its administration. It is discussed possible mechanisms underlying antifibrillatory action of dipeptide GK-1, that, to some extent, may be associated with its ability to change the reactivity of beta-adrenergic structures of the heart.

  2. Arenavirus nucleoprotein targets interferon regulatory factor-activating kinase IKKε.

    Science.gov (United States)

    Pythoud, Christelle; Rodrigo, W W Shanaka I; Pasqual, Giulia; Rothenberger, Sylvia; Martínez-Sobrido, Luis; de la Torre, Juan Carlos; Kunz, Stefan

    2012-08-01

    Arenaviruses perturb innate antiviral defense by blocking induction of type I interferon (IFN) production. Accordingly, the arenavirus nucleoprotein (NP) was shown to block activation and nuclear translocation of interferon regulatory factor 3 (IRF3) in response to virus infection. Here, we sought to identify cellular factors involved in innate antiviral signaling targeted by arenavirus NP. Consistent with previous studies, infection with the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) prevented phosphorylation of IRF3 in response to infection with Sendai virus, a strong inducer of the retinoic acid-inducible gene I (RIG-I)/mitochondrial antiviral signaling (MAVS) pathway of innate antiviral signaling. Using a combination of coimmunoprecipitation and confocal microscopy, we found that LCMV NP associates with the IκB kinase (IKK)-related kinase IKKε but that, rather unexpectedly, LCMV NP did not bind to the closely related TANK-binding kinase 1 (TBK-1). The NP-IKKε interaction was highly conserved among arenaviruses from different clades. In LCMV-infected cells, IKKε colocalized with NP but not with MAVS located on the outer membrane of mitochondria. LCMV NP bound the kinase domain (KD) of IKKε (IKBKE) and blocked its autocatalytic activity and its ability to phosphorylate IRF3, without undergoing phosphorylation. Together, our data identify IKKε as a novel target of arenavirus NP. Engagement of NP seems to sequester IKKε in an inactive complex. Considering the important functions of IKKε in innate antiviral immunity and other cellular processes, the NP-IKKε interaction likely plays a crucial role in arenavirus-host interaction.

  3. Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice.

    Science.gov (United States)

    Umemura, Mariko; Ogura, Tae; Matsuzaki, Ayako; Nakano, Haruo; Takao, Keizo; Miyakawa, Tsuyoshi; Takahashi, Yuji

    2017-01-01

    Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5(-/-)) mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5(-/-) mice were less aggressive than ATF5(+/+) mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5(-/-) mice and wild type littermates. ATF5(-/-) mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5(-/-) mice displayed reduced social interaction in the Crawley's social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5(-/-) mice compared with wild type. In addition, we demonstrated that ATF5(-/-) mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5(-/-) mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5(-/-) mice may be a unique animal model of some psychiatric disorders.

  4. Transcription factor PIF4 controls the thermosensory activation of flowering

    KAUST Repository

    Kumar, S. Vinod

    2012-03-21

    Plant growth and development are strongly affected by small differences in temperature. Current climate change has already altered global plant phenology and distribution, and projected increases in temperature pose a significant challenge to agriculture. Despite the important role of temperature on plant development, the underlying pathways are unknown. It has previously been shown that thermal acceleration of flowering is dependent on the florigen, FLOWERING LOCUS T (FT). How this occurs is, however, not understood, because the major pathway known to upregulate FT, the photoperiod pathway, is not required for thermal acceleration of flowering. Here we demonstrate a direct mechanism by which increasing temperature causes the bHLH transcription factor PHYTOCHROME INTERACTING FACTOR4 (PIF4) to activate FT. Our findings provide a new understanding of how plants control their timing of reproduction in response to temperature. Flowering time is an important trait in crops as well as affecting the life cycles of pollinator species. A molecular understanding of how temperature affects flowering will be important for mitigating the effects of climate change. © 2012 Macmillan Publishers Limited. All rights reserved.

  5. PSYCHOLOGICAL FACTORS OF LABOR ACTIVITY OF ELDERLY MAN

    Directory of Open Access Journals (Sweden)

    Lyusova O.V.

    2016-04-01

    Full Text Available In modern Russian society occurred deformation traditions of respect and maintain the credibility of the elderly, and the socio-economic situation has deteriorated. An important condition to characterize the elderly is related to labor activity. expressed doubts surrounding their professionalism and high-quality and modern education. In society there are negative stereotypes about the elderly: Edil accusations of conservatism, the inability to take risks, tolerance for young. Old age pensioners perceived themselves as age losses, shrinking circle of social contacts, there is social exclusion, significant interpersonal contacts become strained. The psychological diagnosis of labor socialization of older employees 40 people participated. Conducted an empirical study it possible to identify the factors of labor activity in old age: the age and state of health; desire to raise the level of material well-being, the need to work, enthusiasm labor process, achievement motivation, the need for communication with the team; desire for samooaktualizatsii, positive self-esteem, internal locus of control. Working pensioners have high situational anxiety, adequate to the achievement of the objectives, an adequate assessment of its internal and external quality, high life satisfaction, motivation tends to focus on the process and result, reflexivity, subjectivity, have no fear of being rejected, is well adapted to society. Workers older people have average values of introversion, neuroticism, psychoticism.

  6. Platelet-Activating Factor Induces Th17 Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Anne-Marie Drolet

    2011-01-01

    Full Text Available Th17 cells have been implicated in a number of inflammatory and autoimmune diseases. The phospholipid mediator platelet-activating factor (PAF is found in increased concentrations in inflammatory lesions and has been shown to induce IL-6 production. We investigated whether PAF could affect the development of Th17 cells. Picomolar concentrations of PAF induced IL-23, IL-6, and IL-1β expression in monocyte-derived Langerhans cells (LCs and in keratinocytes. Moreover, when LC were pretreated with PAF and then cocultured with anti-CD3- and anti-CD28-activated T cells, the latter developed a Th17 phenotype, with a significant increase in the expression of the transcriptional regulator RORγt and enhanced expression of IL-17, IL-21, and IL-22. PAF-induced Th17 development was prevented by the PAF receptor antagonist WEB2086 and by neutralizing antibodies to IL-23 and IL-6R. This may constitute a previously unknown stimulus for the development and persistence of inflammatory processes that could be amenable to pharmacologic intervention.

  7. Complement factor B activation in patients with preeclampsia.

    Science.gov (United States)

    Velickovic, Ivan; Dalloul, Mudar; Wong, Karen A; Bakare, Olufunke; Schweis, Franz; Garala, Maya; Alam, Amit; Medranda, Giorgio; Lekovic, Jovana; Shuaib, Waqas; Tedjasukmana, Andreas; Little, Perry; Hanono, Daniel; Wijetilaka, Ruvini; Weedon, Jeremy; Lin, Jun; Toledano, Roulhac d'Arby; Zhang, Ming

    2015-06-01

    Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Bb, the active fragment of complement factor B (fB), has been reported to be a predictor of preeclampsia. However, conflicting results have been found by some investigators. We hypothesized that the disagreement in findings may be due to the racial/ethnic differences among various study groups, and that fB activation is significant in women of an ethnic minority with preeclampsia. We investigated the maternal and fetal levels of Bb (the activated fB fragment) in pregnant women of an ethnic minority with or without preeclampsia. We enrolled 291 pregnant women (96% of an ethnic minority, including 78% African-American). Thirteen percent of these were diagnosed with preeclampsia. Maternal venous blood was collected from all participants together with fetal umbilical cord blood samples from 154 deliveries in the 291 women. The results were analyzed using the Mann-Whitney U test and multivariate analyses. Maternal Bb levels were significantly higher in the preeclamptic group than in the nonpreeclamptic group. Levels of Bb in fetal cord blood were similar in both groups. Subgroup analyses of African-American patients' results confirmed the study hypothesis that there would be a significant increase in Bb in the maternal blood of the preeclamptic group and no increase in Bb in the fetal cord blood of this group. These results suggest that a maternal immune response through complement fB might play a role in the development of preeclampsia, particularly in African-American patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2009-02-27

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  9. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2012-02-01

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  10. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW

    2005-01-01

    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive permane

  11. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW

    2005-01-01

    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive

  12. Factoring - financial instrument supporting the current activity of an enterprise

    Directory of Open Access Journals (Sweden)

    Dorota Czerwińska-Kayzer

    2009-01-01

    Full Text Available Small and medium enterprises have a difficult access to classic financial sources. Therefore the factoring could be a financial instrument supporting effective management of the liabilities. Factoring improves the financial situation of a company, first of all financial liquidity. Moreover, factoring improves structure of financial statement and creates a possibility of risk transfer of debtor insolvency on factor.

  13. Sulindac metabolites inhibit epidermal growth factor receptor activation and expression

    Directory of Open Access Journals (Sweden)

    Pangburn Heather A

    2005-09-01

    Full Text Available Abstract Background Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs is associated with a decreased mortality from colorectal cancer (CRC. NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2 signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF receptor (EGFR. Methods HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068, total EGFR, phosphorylated ERK1/2 (pERK1/2, total ERK1/2, activated caspase-3, and α-tubulin. Results EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. Conclusion These results suggest that

  14. Mannoproteins from Cryptococcus neoformans promote dendritic cell maturation and activation.

    Science.gov (United States)

    Pietrella, Donatella; Corbucci, Cristina; Perito, Stefano; Bistoni, Giovanni; Vecchiarelli, Anna

    2005-02-01

    Our previous data show that mannoproteins (MPs) from Cryptococcus neoformans are able to induce protective responses against both C. neoformans and Candida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to IkappaBalpha phosphorylation, which is necessary for nuclear factor kappaB transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi.

  15. Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)

    DEFF Research Database (Denmark)

    Erlandsson, Maria; Nielsen, Carsten Haagen; Jeppesen, Troels Elmer

    2015-01-01

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, th...

  16. Immunomodulator CD200 promotes neurotrophic activity by interacting with and activating the fibroblast growth factor receptor

    DEFF Research Database (Denmark)

    Pankratova, Stanislava; Bjornsdottir, Halla; Christensen, Claus;

    2016-01-01

    in the suppression of microglia activation. We for the first time demonstrated that CD200 can interact with and transduce signaling through activation of the fibroblast growth factor receptor (FGFR), thereby inducing neuritogenesis and promoting neuronal survival in primary neurons. CD200-induced FGFR...... phosphorylation was abrogated by CD200R, whereas FGF2-induced FGFR activation was inhibited by CD200. We also identified a sequence motif located in the first Ig-like module of CD200, likely representing the minimal CD200 binding site for FGFR. The FGFR binding motif overlaps with the CD200R binding site......, suggesting that they can compete for CD200 binding in cells that express both receptors. We propose that CD200 in neurons functions as a ligand of FGFR....

  17. Oxidatively fragmented phosphatidylcholines activate human neutrophils through the receptor for platelet-activating factor.

    Science.gov (United States)

    Smiley, P L; Stremler, K E; Prescott, S M; Zimmerman, G A; McIntyre, T M

    1991-06-15

    Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) activates neutrophils (polymorphonuclear leukocytes, PMN) through a receptor that specifically recognizes short sn-2 residues. We oxidized synthetic [2-arachidonoyl]phosphatidylcholine to fragment and shorten the sn-2 residue, and then examined the phospholipid products for the ability to stimulate PMN. 1-Palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine was fragmented by ozonolysis to 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine. This phospholipid activated human neutrophils at submicromolar concentrations, and is effects were inhibited by specific PAF receptor antagonists WEB2086, L659,989, and CV3988. 1-Palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine next was fragmented by an uncontrolled free radical-catalyzed reaction: it was treated with soybean lipoxygenase to form its sn-2 15-hydroperoxy derivative (which did not activate neutrophils) and then allowed to oxidize under air. The secondary oxidation resulted in the formation of numerous fragmented phospholipids (Stremler, K. E., Stafforini, D. M., Prescott, S. M., and McIntyre, T. M. (1991) J. Biol. Chem. 266, 11095-11103), some of which activated PMN. Hydrolysis of sn-2 residues with phospholipase A2 destroyed biologic activity, as did hydrolysis with PAF acetylhydrolase. PAF acetylhydrolase is specific for short or intermediate length sn-2 residues and does not hydrolyze the starting material (Stremler, K. E., Stafforini, D. M., Prescott, S. M., and McIntyre, T. M. (1991) J. Biol. Chem. 266, 11095-11103). Neutrophil activation was completely blocked by L659,989, a specific PAF receptor antagonist. We conclude that diacylphosphatidylcholines containing an sn-2 polyunsaturated fatty acyl residue can be oxidatively fragmented to species with sn-2 residues short enough to activate the PAF receptor of neutrophils. This suggests a new mechanism for the appearance of biologically active phospholipids, and shows

  18. Regulation of MSK1-Mediated NF-κB Activation Upon UVB Irradiation.

    Science.gov (United States)

    Carpenter, Oliver L; Wu, Shiyong

    2014-01-01

    Nuclear Factor Kappa-B (NF-κB) is a transcription factor that controls expression of genes involved in the immune and inflammatory responses as well as being a key component in the onset of cancers. In this study, we provided evidence that mitogen- and stress-activated protein kinase (MSK1) is responsible for a noncanonical late-phase activation of NF-κB upon UVB irradiation. Our data demonstrated that following UVB irradiation, MSK1 is activated via phosphorylation at the 24 h time point coinciding with translocation of NF-κB into the nucleus. Investigations into the signaling pathways upstream of MSK1 through the use of specific inhibitors for mitogen-activated protein kinase and p38 revealed that both kinases are required for full phosphorylation during the late phase (24 h), while p38 is paramount for phosphorylation during the early phase (6 h). Electromobility shift assays (EMSA) showed that inhibition of MSK1 resulted in a marked reduction in NF-κB binding affinity without altering the nuclear translocation of NF-κB. Supershift EMSA implicate that the p65, but not p50, isoform of NF-κB is involved in late-phase activation in response to UVB irradiation. Together, the results of these studies shed light onto a novel pathway of MSK1-mediated late-phase activation of NF-κB in response to UVB irradiation.

  19. Stimulation of Leishmania tropica protein kinase CK2 activities by platelet-activating factor (PAF).

    Science.gov (United States)

    Dutra, Patricia M L; Vieira, Danielle P; Meyer-Fernandes, Jose R; Silva-Neto, Mario A C; Lopes, Angela H

    2009-09-01

    Leishmania tropica is one of the causative agents of cutaneous leishmaniasis. Platelet-activating factor (PAF) is a phospholipid mediator in diverse biological and pathophysiological processes. Here we show that PAF promoted a three-fold increase on ecto-protein kinase and a three-fold increase on the secreted kinase activity of L. tropica live promastigotes. When casein was added to the reaction medium, along with PAF, there was a four-fold increase on the ecto-kinase activity. When live L. tropica promastigotes were pre-incubated for 30 min in the presence of PAF-plus casein, a six-fold increase on the secreted kinase activity was observed. Also, a protein released from L. tropica promastigotes reacted with polyclonal antibodies for the mammalian CK2 alpha catalytic subunit. Furthermore, in vitro mouse macrophage infection by L. tropica was doubled when promastigotes were pre-treated for 2 h with PAF. Similar results were obtained when the interaction was performed in the presence of purified CK2 or casein. TBB and DRB, CK2 inhibitors, reversed PAF enhancement of macrophage infection by L. tropica. WEB 2086, a competitive PAF antagonist, reversed all PAF effects here described. This study shows for the first time that PAF promotes the activation of two isoforms of CK2, secreted and membrane-bound, correlating these activities to infection of mouse macrophages.

  20. Recombinant activated factor VII in post partum haemorrhage

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2013-01-01

    Full Text Available Post-partum haemorrhage (PPH is a life-threatening obstetric complication and the leading cause of maternal death. Any bleeding that results in or could result in haemodynamic instability, if untreated, must be considered as PPH. There is no controversy about the need for prevention and treatment of PPH. The keystone of management of PPH entails first, non-invasive and nonsurgical methods and then invasive and surgical methods. However, mortality remains high. Therefore, new advancements in the treatment are most crucial. One such advancement has been the use of recombinant activated factor VII (rFVIIa in PPH. First used 12 years back in PPH, this universal haemostatic agent has been effectively used in controlling PPH. The best available indicator of rFVIIa efficacy is the arrest of haemorrhage, which is judged by visual evidence and haemodynamic stabilization. It also reduces costs of therapy and the use of blood components in massive PPH. In cases of intractable PPH with no other obvious indications for hysterectomy, administration of rFVIIa should be considered before surgery. We share our experience in a series of cases of PPH, successfully managed using rFVIIa.

  1. Factors influencing quality of life in patients with active tuberculosis

    Directory of Open Access Journals (Sweden)

    Cox Victoria C

    2004-10-01

    Full Text Available Abstract Background With effective treatment strategies, the focus of tuberculosis (TB management has shifted from the prevention of mortality to the avoidance of morbidity. As such, there should be an increased focus on quality of life (QoL experienced by individuals being treated for TB. The objective of our study was to identify areas of QoL that are affected by active TB using focus groups and individual interviews. Methods English, Cantonese, and Punjabi-speaking subjects with active TB who were receiving treatment were eligible for recruitment into the study. Gender-based focus group sessions were conducted for the inner city participants but individual interviews were conducted for those who came to the main TB clinic or were hospitalized. Facilitators used open-ended questions and participants were asked to discuss their experiences of being diagnosed with tuberculosis, what impact it had on their lives, issues around adherence to anti-TB medications and information pertaining to their experience with side effects to these medications. All data were audio-recorded, transcribed verbatim, and analyzed using constant comparative analysis. Results 39 patients with active TB participated. The mean age was 46.2 years (SD 18.4 and 62% were male. Most were Canadian-born being either Caucasian or Aboriginal. Four themes emerged from the focus groups and interviews. The first describes issues related to the diagnosis of tuberculosis and sub-themes were identified as 'symptoms', 'health care provision', and 'emotional impact'. The second theme discusses TB medication factors and the sub-themes identified were 'adverse effects', 'ease of administration', and 'adherence'. The third theme describes social support and functioning issues for the individuals with TB. The fourth theme describes health behavior issues for the individuals with TB and the identified sub-themes were "behavior modification" and "TB knowledge." Conclusion Despite the ability to

  2. Influence of Environmental Factors on Feammox Activity in Soil Environments

    Science.gov (United States)

    Huang, S.; Jaffe, P. R.

    2015-12-01

    The oxidation of ammonium (NH4+) under iron reducing conditions, referred to as Feammox, has been described in recent years by several investigators. The environmental characteristics in which the Feammox process occurs need to be understood in order to determine its contribution to the nitrogen cycle. In this study, a total of 66 locations were selected covering 4 different types of soils/sediments: wetland soils (W), river sediments (R), forest soils (F), and paddy soils (P) from several locations in central New Jersey, at Tims Branch at Savannah River in South Carolina, both in the Unities States, and at several locations in the Guangdong province in China. Though soil chemical analyses, serial culturing experiments, analysis of microbial communities, and using a canonical correspondence analysis, the occurrence of the Feammox reaction and the presence of Acidimicrobiaceae bacterium A6, which plays a key role in the Feammox process(1), were found in 17 samples. Analyses showed that the soil pH, as well as its Fe(III) and NH4+ content were the most important factors controlling the distribution of these Feammox microorganisms. Based on the results, soils in the subtropical forests and soils that are near agricultural areas could be Feammox hotspot. Under the conditions that favor the presence and activity of Feammox microorganisms and their oxidation of NH4+, denitrification bacteria were also active. However, the presence of nitrous oxide (N2O) reducers was limited under these conditions, implying that at locations where the Feammox process is active, conditions are favoring a higher ratio of N2O: N2 as the nitrogen (N) end products. Incubations of soils where the presence of Acidimicrobiaceae bacterium A6 was detected, were conducted for 120 days under two different DO levels (DO ammonia-oxidizing bacteria and anammox bacteria) decreased, while in the incubations with DO = 0.8~1.0 mg/L the opposite trend was observed. References Huang S., and Jaffé P.R., 2015

  3. Azadirachtin interacts with the tumor necrosis factor (TNF) binding domain of its receptors and inhibits TNF-induced biological responses.

    Science.gov (United States)

    Thoh, Maikho; Kumar, Pankaj; Nagarajaram, Hampathalu A; Manna, Sunil K

    2010-02-19

    The role of azadirachtin, an active component of a medicinal plant Neem (Azadirachta indica), on TNF-induced cell signaling in human cell lines was investigated. Azadirachtin blocks TNF-induced activation of nuclear factor kappaB (NF-kappaB) and also expression of NF-kappaB-dependent genes such as adhesion molecules and cyclooxygenase 2. Azadirachtin inhibits the inhibitory subunit of NF-kappaB (IkappaB alpha) phosphorylation and thereby its degradation and RelA (p65) nuclear translocation. It blocks IkappaB alpha kinase (IKK) activity ex vivo, but not in vitro. Surprisingly, azadirachtin blocks NF-kappaB DNA binding activity in transfected cells with TNF receptor-associated factor (TRAF)2, TNF receptor-associated death domain (TRADD), IKK, or p65, but not with TNFR, suggesting its effect is at the TNFR level. Azadirachtin blocks binding of TNF, but not IL-1, IL-4, IL-8, or TNF-related apoptosis-inducing ligand (TRAIL) with its respective receptors. Anti-TNFR antibody or TNF protects azadirachtin-mediated down-regulation of TNFRs. Further, in silico data suggest that azadirachtin strongly binds in the TNF binding site of TNFR. Overall, our data suggest that azadirachtin modulates cell surface TNFRs thereby decreasing TNF-induced biological responses. Thus, azadirachtin exerts an anti-inflammatory response by a novel pathway, which may be beneficial for anti-inflammatory therapy.

  4. Genome-wide signatures of transcription factor activity: connecting transcription factors, disease, and small molecules.

    Directory of Open Access Journals (Sweden)

    Jing Chen

    Full Text Available Identifying transcription factors (TF involved in producing a genome-wide transcriptional profile is an essential step in building mechanistic model that can explain observed gene expression data. We developed a statistical framework for constructing genome-wide signatures of TF activity, and for using such signatures in the analysis of gene expression data produced by complex transcriptional regulatory programs. Our framework integrates ChIP-seq data and appropriately matched gene expression profiles to identify True REGulatory (TREG TF-gene interactions. It provides genome-wide quantification of the likelihood of regulatory TF-gene interaction that can be used to either identify regulated genes, or as genome-wide signature of TF activity. To effectively use ChIP-seq data, we introduce a novel statistical model that integrates information from all binding "peaks" within 2 Mb window around a gene's transcription start site (TSS, and provides gene-level binding scores and probabilities of regulatory interaction. In the second step we integrate these binding scores and regulatory probabilities with gene expression data to assess the likelihood of True REGulatory (TREG TF-gene interactions. We demonstrate the advantages of TREG framework in identifying genes regulated by two TFs with widely different distribution of functional binding events (ERα and E2f1. We also show that TREG signatures of TF activity vastly improve our ability to detect involvement of ERα in producing complex diseases-related transcriptional profiles. Through a large study of disease-related transcriptional signatures and transcriptional signatures of drug activity, we demonstrate that increase in statistical power associated with the use of TREG signatures makes the crucial difference in identifying key targets for treatment, and drugs to use for treatment. All methods are implemented in an open-source R package treg. The package also contains all data used in the analysis

  5. Mechanism of surface-mediated activation of bovine Factor XII and prekallikrein.

    Science.gov (United States)

    Sugo, T; Ohno, Y; Shimada, T; Kato, H; Iwanaga, S

    1983-01-01

    The mechanism of kaolin-mediated activation of bovine Factor XII was studied in the presence of prekallikrein and HMW kininogen. The activated enzymes were assayed using fluorogenic peptides, Boc-Glu (OBzl)-Gly-Arg-4-methylcoumaryl-7-amide (MCA) for Factor XIIa and Z-Phe-Arg-MCA for plasma kallikrein. The rates of activation of the zymogens were separately measured by blocking either of the active enzymes with specific inhibitors, corn inhibitor for Factor XIIa (Ki = 6.7 nM) and Trasylol for plasma kallikrein (Ki = 3.9 nM). The result was as follows: (1) At the early stage of the activation reaction, kallikrein activity was first generated after short lag time, and then Factor XIIa activity was generated with a sigmoidal curve. In the presence of corn inhibitor, the activation of prekallikrein was observed, but in the presence of Trasylol, the activation of Factor XII was not observed. In the presence of high concentration of Ala-Phe-Arg-Ch2Cl, which inactivates immediately both of the active enzymes, the cleavage of a single chain prekallikrein into the two chain form by Factor XII was shown by SDS-PAGE, using nonlabelled and tritiated prekallikrein. (2) The incubation of Factor XII alone in a quartz cuvette or in the presence of kaolin and HMW kininogen did not result in the activation of Factor XII. The concave upward curve due to an autocatalytic activation was not observed even after the addition of Factor XIIa to Factor XII preparation. Moreover, no structural change of Factor XII during the incubation with kaolin and HMW kininogen was shown by SDS-PAGE, using 3H-Factor XII. (3) The rates of activation of prekallikrein by Factor XII and by Factor XIIa were approximately the same at higher concentration of prekallikrein. However, at lower concentration of prekallikrein the rate of activation of prekallikrein by Factor XII was shown to be a sigmoidal curve and slower than that by Factor XIIa. These results indicate that the activation of bovine Factor XII is

  6. Platelet-activating factor (PAF) receptor-binding antagonist activity of Malaysian medicinal plants.

    Science.gov (United States)

    Jantan, I; Rafi, I A A; Jalil, J

    2005-01-01

    Forty-nine methanol extracts of 37 species of Malaysian medicinal plants were investigated for their inhibitory effects on platelet-activating factor (PAF) binding to rabbit platelets, using 3H-PAF as a ligand. Among them, the extracts of six Zingiberaceae species (Alpinia galanga Swartz., Boesenbergia pandurata Roxb., Curcuma ochorrhiza Val., C. aeruginosa Roxb., Zingiber officinale Rosc. and Z. zerumbet Koenig.), two Cinnamomum species (C. altissimum Kosterm. and C. pubescens Kochummen.), Goniothalamus malayanus Hook. f. Momordica charantia Linn. and Piper aduncum L. are potential sources of new PAF antagonists, as they showed significant inhibitory effects with IC50 values ranging from 1.2 to 18.4 microg ml(-1).

  7. Morin modulates the oxidative stress-induced NF-kappaB pathway through its anti-oxidant activity.

    Science.gov (United States)

    Kim, Ji Min; Lee, Eun Kyeong; Park, Gwangli; Kim, Mi Kyung; Yokozawa, Takako; Yu, Byung Pal; Chung, Hae Young

    2010-04-01

    Morin is a flavone that has anti-inflammatory effects through a mechanism that is not well understood. Based on the extreme sensitive nature of the transcription factor, NF-kB to redox change, it is postulated that morin's anti-NF-kappaB activation likely depends on its ability to scavenge excessive reactive species [RS]. The present study assessed the extent of morin's ability to modulate RS-induced NF-kappaB activation through its scavenging activity. Results indicate that morin neutralized RS in vitro and inhibited t-BHP-induced RS generation. It also examined morin for suppressed redox-sensitive transcription factor NF-kappaB activation via reduced DNA binding activity, I kappaB alpha phosphorylation and p65/p50 nuclear translocation. The more important finding was that suppression of the NF-kappaB cascade by morin was modulated through the ERK and p38 MAPKs signal transduction pathways in endothelial cells. As a consequence, morin's anti-oxidant effect extended expression level of NF-kappaB dependent pro-inflammatory genes, thereby reducing COX-2, iNOS and 5-LOX. The data indicate that morin has strong anti-oxidative power against RS-induced NF-kappaB modulation through the ERK and p38 MAPKs signalling pathways by its RS scavenging activity. The significance of the current study is the new revelation that morin may have potential as an effective anti-inflammatory therapeutic agent.

  8. State support as factor of increase of innovative activity of industrial enterprises

    Directory of Open Access Journals (Sweden)

    N.N. Bondarenko

    2011-10-01

    Full Text Available The article is devoted research of factors of increase of innovative activity of enterprise, the indexes of innovative activity of industrial enterprises are analysed in Ukraine, the necessity of creation of attractive terms is grounded for development of innovative activity and increase of innovative activity of management subjects at state level, the forms of state support as factor of increase of innovative activity of industrial enterprises are considered.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Factor XI and Contact Activation as Targets for Antithrombotic Therapy

    OpenAIRE

    Gailani, David; Bane, Charles E.; Gruber, Andras

    2015-01-01

    The most commonly used anticoagulants produce therapeutic antithrombotic effects either by inhibiting thrombin or factor Xa, or by lowering the plasma levels of the precursors of these key enzymes, prothrombin and factor X. These drugs do not distinguish between thrombin generation contributing to thrombosis from thrombin generation required for hemostasis. Thus, anticoagulants increase bleeding risk, and many patients who would benefit from therapy go untreated because of comorbidities that ...

  11. Tumour necrosis factor production and natural killer cell activity in peripheral blood during treatment with recombinant tumour necrosis factor

    OpenAIRE

    Männel, Daniela N.; Kist, A.; Ho, A D; Räth, U.; Reichardt, P; Wiedenmann, B; Schlick, E.; Kirchner, H.

    1989-01-01

    Tumour necrosis factor (TNF) has been found to be an important immunomodulator. Among other functions TNF activates natural killer (NK) cells and stimulates monocytes/macrophages in an autocrine fashion. TNF production and NK activity in peripheral blood mononuclear cells were determined in a clinical phase I study in which recombinant human (rh) TNF was administered as a continuous infusion weekly for a period of 8 weeks. Even though TNF production and NK activity were significantly reduced ...

  12. Physical Activity among Older People and Related Factors

    Science.gov (United States)

    Persson, Ann; While, Alison

    2012-01-01

    Objective: To investigate the duration, intensity and type of physical activity undertaken by people aged 60 years and over in relation to their reported levels of participation in social activities and their perceptions of their neighbourhood. Design: A cross-sectional questionnaire survey of older people attending two luncheon and eight social…

  13. Building gene expression signatures indicative of transcription factor activation to predict AOP modulation

    Science.gov (United States)

    Building gene expression signatures indicative of transcription factor activation to predict AOP modulation Adverse outcome pathways (AOPs) are a framework for predicting quantitative relationships between molecular initiatin...

  14. The Role of Platelet-Activating Factor in Chronic Inflammation, Immune Activation, and Comorbidities Associated with HIV Infection

    Science.gov (United States)

    Kelesidis, Theodoros; Papakonstantinou, Vasiliki; Detopoulou, Paraskevi; Fragopoulou, Elizabeth; Chini, Maria; Lazanas, Marios C.; Antonopoulou, Smaragdi

    2016-01-01

    With the advent of highly effective antiretroviral therapy, cardiovascular disease has become an important cause of morbidity and mortality among people with treated HIV-1, but the pathogenesis is unclear. Platelet-activating factor is a potent lipid mediator of inflammation that has immunomodulatory effects and a pivotal role in the pathogenesis of inflammatory disorders and cardiovascular disease. Limited scientific evidence suggests that the platelet-activating factor pathway may be a mechanistic link between HIV-1 infection, systemic inflammation, and immune activation that contribute to pathogenesis of chronic HIV-related comorbidities, including cardiovascular disease and HIV-associated neurocognitive disorders. In this review, we examine the mechanisms by which the cross-talk between HIV-1, immune dysregulation, inflammation, and perturbations in the platelet-activating factor pathway may directly affect HIV-1 immunopathogenesis. Understanding the role of platelet-activating factor in HIV-1 infection may pave the way for further studies to explore therapeutic interventions, such as diet, that can modify platelet-activating factor activity and use of platelet-activating factor inhibitors that might improve the prognosis of HIV-1 infected patients. PMID:26616844

  15. Impact of nonsynonymous mutations of factor X on the functions of factor X and anticoagulant activity of edoxaban.

    Science.gov (United States)

    Noguchi, Kengo; Morishima, Yoshiyuki; Takahashi, Shinichi; Ishihara, Hiroaki; Shibano, Toshiro; Murata, Mitsuru

    2015-03-01

    Edoxaban is an oral direct factor Xa (FXa) inhibitor and its efficacy as an oral anticoagulant is less subject to drug-food and drug-drug interaction than existing vitamin K antagonists. Although this profile of edoxaban suggests it is well suited for clinical use, it is not clear whether genetic variations of factor X influence the activity of edoxaban. Our aim was to investigate a possible impact of single-nucleotide polymorphisms (SNPs) in the factor X gene on the functions of factor X and the activity of edoxaban. Two nonsynonymous SNPs within mature factor X, Ala152Thr and Gly192Arg, were selected as possible candidates that might affect the functions of FXa and the activity of edoxaban. We measured catalytic activities of wild type and mutant FXas in a chromogenic assay using S-2222 and coagulation times including prothrombin time (PT) and activated partial thrombin time (aPTT) of plasma-containing recombinant FXs in the presence and absence of edoxaban. Michaelis-Menten kinetic parameters of FXas, Km and Vmax values, PT and aPTT were not influenced by either mutation indicating these mutations do not affect the FXa catalytic and coagulation activities. The Ki values of edoxaban for the FXas and the concentrations of edoxaban required to double PT and aPTT were not different between wild type and mutated FXas indicating that both mutations have little impact on the activity of edoxaban. In conclusion, these data suggest that edoxaban has little interpatient variability stemming from SNPs in the factor X gene.

  16. Factors affecting teachers' participation in professional learning activities

    NARCIS (Netherlands)

    Kwakman, C.H.E.

    2003-01-01

    This paper describes two studies into teacher workplace learning. The first study aimed at developing a definition of teacher learning at the workplace and at exploring factors that may affect teacher learning at the workplace. Based on a conceptualization of teacher workplace learning as

  17. Active von Willebrand factor in thrombotic thrombocytopenic purpura and malaria

    NARCIS (Netherlands)

    Groot, E.

    2009-01-01

    Thrombotic thrombocytopenic purpura (TTP) and malaria are two diseases of distinct origin. TTP is a rare disorder caused by a deficiency of the von Willebrand factor (VWF) cleaving protease ADAMTS13. Malaria is a poverty-related disease caused by protozoan parasites from the genus Plasmodium. TTP an

  18. Key factors governing alkaline pretreatment of waste activated sludge

    Institute of Scientific and Technical Information of China (English)

    Xianli Shi; Li Deng; Fangfang Sun; Jieyu Liang; Xu Deng

    2015-01-01

    Alkaline pretreatment is an effective technology to disintegrate sewage sludge, where alkali dosage and sludge concentration are two important factors. pH value or alkali concentration is usually adjusted in order to deter-mine a proper dosage of alkali. Our work has found that this is not a good strategy. A new parameter, the ratio of alkali to sludge (Ra/s), is more sensitive in controlling the alkali dosage. The sludge concentration Cs and reten-tion time t are two other important factors to consider. The validity of these arguments is confirmed with model-ing and experiments. The individual effect of Ra/s, Cs and t was studied separately. Then the combined effect of these three factors was evaluated. The sludge disintegration degree of 44.7%was achieved with the optimized factors. Furthermore, an alkaline-microwave combined pretreatment process was carried out under these optimized conditions. A high disintegration degree of 62.3%was achieved while the energy consumption of microwave was much lower than previously reported.

  19. A MATHEMATICAL MODEL FOR ASSESSING THE FACTORING ACTIVITY

    Directory of Open Access Journals (Sweden)

    Madalina Radoi

    2013-11-01

    Full Text Available Originally–being over 4,000 years old–factoring was first used in the fertile territory of old Mesopotamia at a time when the famous Code of Hammurabi was drawn up. However, many years passed until the British colonists started to use it on a large scale at a time when the metropolis would pay them sums of money for the merchandise that colonists sent to the old continent until they collected the invoices.In Romania factoring started to play a major role in financial operations for it led to the increase of liquidities on the market.According to the Romanian legislation, factoring is a contract concluded between a party known as “the client”, which supplies merchandise or provides services, and a banking institution or specialized financial institution known as “the factor”, whereby the latter ensures the financing source, collects the receivables and protects credit risks, while the client assigns to the factor the receivables resulting from the sale of goods or the provision of services to third parties.

  20. Situational and Personality Factors: Interactive Effects on Attitude - Active Consistency

    Science.gov (United States)

    Albrecht, Stan L.; Warner, Lyle G.

    1975-01-01

    An examination of the combined effect of a situational factor, disclosure, and two personality variables, "need for approval" and "inner-other directedness" on attitude - action relationships with respect to marijuana related attitudes and behavior of college students. Subjects with different personality characteristics were found to respond…

  1. Factors influencing quality of life in patients with active tuberculosis

    OpenAIRE

    Cox Victoria C; Marra Fawziah; Marra Carlo A; Palepu Anita; FitzGerald J Mark

    2004-01-01

    Abstract Background With effective treatment strategies, the focus of tuberculosis (TB) management has shifted from the prevention of mortality to the avoidance of morbidity. As such, there should be an increased focus on quality of life (QoL) experienced by individuals being treated for TB. The objective of our study was to identify areas of QoL that are affected by active TB using focus groups and individual interviews. Methods English, Cantonese, and Punjabi-speaking subjects with active T...

  2. (111)Indium Labelling of Recombinant Activated Coagulation Factor VII

    DEFF Research Database (Denmark)

    Nalla, Amarnadh; Buch, Inge; Sigvardt, Maibritt

    2012-01-01

    . administration of 1.6-1.8 MBq (111)In-DTPA-rFVIIa up to 120-130 min. Five min after administration of (111)In-DTPA-rFVIIa, percentage of (111)In activity was 6.0% in the cardiac region and 24.5% in the liver region. After 2 hours activity was decreased to 3.3% in heart while it had increased to 42...

  3. Cisplatin induces cytotoxicity through the mitogen-activated protein kinase pathways and activating transcription factor 3.

    Science.gov (United States)

    St Germain, Carly; Niknejad, Nima; Ma, Laurie; Garbuio, Kyla; Hai, Tsonwin; Dimitroulakos, Jim

    2010-07-01

    The mechanisms underlying the proapoptotic effect of the chemotherapeutic agent, cisplatin, are largely undefined. Understanding the mechanisms regulating cisplatin cytotoxicity may uncover strategies to enhance the efficacy of this important therapeutic agent. This study evaluates the role of activating transcription factor 3 (ATF3) as a mediator of cisplatin-induced cytotoxicity. Cytotoxic doses of cisplatin and carboplatin treatments consistently induced ATF3 expression in five tumor-derived cell lines. Characterization of this induction revealed a p53, BRCA1, and integrated stress response-independent mechanism, all previously implicated in stress-mediated ATF3 induction. Analysis of mitogen-activated protein kinase (MAPK) pathway involvement in ATF3 induction by cisplatin revealed a MAPK-dependent mechanism. Cisplatin treatment combined with specific inhibitors to each MAPK pathway (c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38) resulted in decreased ATF3 induction at the protein level. MAPK pathway inhibition led to decreased ATF3 messenger RNA expression and reduced cytotoxic effects of cisplatin as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay. In A549 lung carcinoma cells, targeting ATF3 with specific small hairpin RNA also attenuated the cytotoxic effects of cisplatin. Similarly, ATF3-/- murine embryonic fibroblasts (MEFs) were shown to be less sensitive to cisplatin-induced cytotoxicity compared with ATF3+/+ MEFs. This study identifies cisplatin as a MAPK pathway-dependent inducer of ATF3, whose expression influences cisplatin's cytotoxic effects.

  4. Kaurane diterpenes protect against apoptosis and inhibition of phagocytosis in activated macrophages.

    Science.gov (United States)

    de las Heras, B; Hortelano, S; Girón, N; Bermejo, P; Rodríguez, B; Boscá, L

    2007-09-01

    The kaurane diterpenes foliol and linearol are inhibitors of the activation of nuclear factor kappaB, a transcription factor involved in the inflammatory response. Effects of these diterpenes on apoptosis and phagocytosis have been analysed in cultured peritoneal macrophages and in the mouse macrophage cell line, RAW 264.7. Macrophages were maintained in culture and activated with pro-inflammatory stimuli in the absence or presence of diterpenes. Apoptosis and the phagocytosis in these cells under these conditions were determined. Incubation of macrophages with a mixture of bacterial lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) induced apoptosis through a NO-dependent pathway, an effect significantly inhibited by foliol and linearol in the low muM range, without cytotoxic effects. Apoptosis in macrophages induced by NO donors was also inhibited. The diterpenes prevented apoptosis through a mechanism compatible with the inhibition of caspase-3 activation, release of cytochrome c to the cytosol and p53 overexpression, as well as an alteration in the levels of proteins of the Bcl-2 family, in particular, the levels of Bax. Cleavage of poly(ADP-ribose) polymerase, a well-established caspase substrate, was reduced by these diterpenes. Treatment of cells with foliol and linearol decreased phagocytosis of zymosan bioparticles by RAW 264.7 cells and to a greater extent by peritoneal macrophages. Both diterpenes protected macrophages from apoptosis and inhibited phagocytosis, resulting in a paradoxical control of macrophage function, as viability was prolonged but inflammatory and phagocytic functions were impaired.

  5. Failure of apoptosis and activation on NFkappaB by celecoxib and aspirin in lung cancer cell lines.

    Science.gov (United States)

    Gradilone, Angela; Silvestri, Ida; Scarpa, Susanna; Morrone, Stefania; Gandini, Orietta; Pulcinelli, Fabio M; Gianni, Walter; Frati, Luigi; Aglianò, Anna Maria; Gazzaniga, Paola

    2007-04-01

    Recent studies have demonstrated that antineoplastic activity of Cox-2 inhibitors may depend on targets other than Cox: among those, nuclear factor kappaB (NFkappaB) seems the most promising. Although preclinical studies have suggested that aspirin and Cox-2 inhibitors may influence the progression of lung cancer, the molecular mechanisms of these protective effects in this tumor type has not been fully elucidated. We investigated the effects of celecoxib and aspirin in the induction of apoptosis and in the ability to activate NFkappaB in three non-small cell lung cancer cell lines. Apoptosis was evaluated by FACS, caspase activation assay and expression of apoptosis-related genes by RT-PCR, while NFkappaB activation was assessed by immunofluorescence. No apoptotic response was observed after treatment with both high and low dose of celecoxib. Nevertheless, celecoxib at both concentrations induced a strong NFkappaB activation, with increased expression of NFkappaB-dependent genes, such as bcl-2, bcl-XL and survivin. Similarly, aspirin at both concentrations did not induce any apoptotic response, but activated NFkappaB in a dose-dependent manner. This study supports the hypothesis that NFkappaB activation is an important effect of NSAIDs in lung cancer, leading to apoptosis resistance. This effect of both aspirin and celecoxib may be considered undesirable in lung cancer chemoprevention.

  6. Antioxidant Activity of γ-Oryzanol: A Complex Network of Interactions

    Directory of Open Access Journals (Sweden)

    Igor Otavio Minatel

    2016-08-01

    Full Text Available γ-oryzanol (Orz, a steryl ferulate extracted from rice bran layer, exerts a wide spectrum of biological activities. In addition to its antioxidant activity, Orz is often associated with cholesterol-lowering, anti-inflammatory, anti-cancer and anti-diabetic effects. In recent years, the usefulness of Orz has been studied for the treatment of metabolic diseases, as it acts to ameliorate insulin activity, cholesterol metabolism, and associated chronic inflammation. Previous studies have shown the direct action of Orz when downregulating the expression of genes that encode proteins related to adiposity (CCAAT/enhancer binding proteins (C/EBPs, inflammatory responses (nuclear factor kappa-B (NF-κB, and metabolic syndrome (peroxisome proliferator-activated receptors (PPARs. It is likely that this wide range of beneficial activities results from a complex network of interactions and signals triggered, and/or inhibited by its antioxidant properties. This review focuses on the significance of Orz in metabolic disorders, which feature remarkable oxidative imbalance, such as impaired glucose metabolism, obesity, and inflammation.

  7. Differential requirement of the epidermal growth factor receptor for G protein-mediated activation of transcription factors by lysophosphatidic acid

    Directory of Open Access Journals (Sweden)

    Dent Paul

    2010-01-01

    Full Text Available Abstract Background The role of the epidermal growth factor receptor (EGFR and other receptor tyrosine kinases (RTKs in provoking biological actions of G protein-coupled receptors (GPCRs has been one of the most disputed subjects in the field of GPCR signal transduction. The purpose of the current study is to identify EGFR-mediated mechanisms involved in activation of G protein cascades and the downstream transcription factors by lysophosphatidic acid (LPA. Results In ovarian cancer cells highly responsive to LPA, activation of AP-1 by LPA was suppressed by inhibition of EGFR, an effect that could be reversed by co-stimulation of another receptor tyrosine kinase c-Met with hepatocyte growth factor, indicating that LPA-mediated activation of AP-1 requires activity of a RTK, not necessarily EGFR. Induction of AP-1 components by LPA lied downstream of Gi, G12/13, and Gq. Activation of the effectors of Gi, but not Gq or G12/13 was sensitive to inhibition of EGFR. In contrast, LPA stimulated another prominent transcription factor NF-κB via the Gq-PKC pathway in an EGFR-independent manner. Consistent with the importance of Gi-elicited signals in a plethora of biological processes, LPA-induced cytokine production, cell proliferation, migration and invasion require intact EGFR. Conclusions An RTK activity is required for activation of the AP-1 transcription factor and other Gi-dependent cellular responses to LPA. In contrast, activation of G12/13, Gq and Gq-elicited NF-κB by LPA is independent of such an input. These results provide a novel insight into the role of RTK in GPCR signal transduction and biological functions.

  8. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    Energy Technology Data Exchange (ETDEWEB)

    Bitencourt, C.S. [Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I. [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-02

    Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

  9. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    Directory of Open Access Journals (Sweden)

    C.S. Bitencourt

    2012-03-01

    Full Text Available Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP activity in male Wistar rats (180 ± 10 g after altering their thyroid hormone levels by treatment with triiodothyronine (T3, propylthiouracil (PTU or thyroidectomy. T3 and thyroxine (T4 levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg. Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01. In contrast, increased factor B concentration and activity (32% were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

  10. Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: impact of active tissue factor.

    Science.gov (United States)

    Shustova, Olga N; Antonova, Olga A; Golubeva, Nina V; Khaspekova, Svetlana G; Yakushkin, Vladimir V; Aksuk, Svetlana A; Alchinova, Irina B; Karganov, Mikhail Y; Mazurov, Alexey V

    2016-12-06

    Microparticles released by activated/apoptotic cells exhibit coagulation activity as they express phosphatidylserine and some of them - tissue factor. We compared procoagulant properties of microparticles from monocytes, granulocytes, platelets and endothelial cells and assessed the impact of tissue factor in observed differences. Microparticles were sedimented (20 000g, 30 min) from the supernatants of activated monocytes, monocytic THP-1 cells, granulocytes, platelets and endothelial cells. Coagulation activity of microparticles was examined using plasma recalcification assay. The size of microparticles was evaluated by dynamic light scattering. Tissue factor activity was measured by its ability to activate factor X. All microparticles significantly accelerated plasma coagulation with the shortest lag times for microparticles derived from monocytes, intermediate - for microparticles from THP-1 cells and endothelial cells, and the longest - for microparticles from granulocytes and platelets. Average diameters of microparticles ranged within 400-600 nm. The largest microparticles were produced by endothelial cells and granulocytes, smaller - by monocytes, and the smallest - by THP-1 cells and platelets. The highest tissue factor activity was detected in microparticles from monocytes, lower activity - in microparticles from endothelial cells and THP-1 cells, and no activity - in microparticles from platelets and granulocytes. Anti-tissue factor antibodies extended coagulation lag times for microparticles from monocytes, endothelial cells and THP-1 cells and equalized them with those for microparticles from platelets and granulocytes. Higher coagulation activity of microparticles from monocytes, THP-1 cells and endothelial cells in comparison with microparticles from platelets and granulocytes is determined mainly by the presence of active tissue factor.

  11. Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-related factor 2 pathway.

    Science.gov (United States)

    Fischedick, Justin T; Standiford, Miranda; Johnson, Delinda A; Johnson, Jeffrey A

    2013-05-01

    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate cytoprotective genes which may be useful in the treatment of neurodegenerative disease. In order to better understand the structure activity relationship of phenolic diterpenes from Salvia officinalis L., we isolated carnosic acid, carnosol, epirosmanol, rosmanol, 12-methoxy-carnosic acid, sageone, and carnosaldehyde using polyamide column, centrifugal partition chromatography, and semi-preparative high performance liquid chromatography. Isolated compounds were screened in vitro for their ability to active the Nrf2 and general cellular toxicity using mouse primary cortical cultures. All compounds except 12-methoxy-carnosic acid were able to activate the antioxidant response element. Furthermore both carnosol and carnoasldehyde were able to induce Nrf2-dependent gene expression as well as protect mouse primary cortical neuronal cultures from H(2)O(2) induced cell death.

  12. Relation of physical activity to cardiovascular disease mortality and the influence of cardiometabolic risk factors.

    Science.gov (United States)

    Reddigan, Jacinta I; Ardern, Chris I; Riddell, Michael C; Kuk, Jennifer L

    2011-11-15

    Physical activity can improve several metabolic risk factors associated with cardiovascular disease (CVD) and is associated with a lower risk of CVD mortality. We sought to evaluate the extent to which metabolic risk factors mediate the association between physical activity and CVD mortality and whether physical activity provides protective effects against CVD mortality in healthy adults and those with metabolic risk factors. A sample of 10,261 adults from the Third National Health and Nutrition Examination Survey with public-access mortality data linkage (follow-up 13.4 ± 3.9 years) was used. Physical activity was assessed by questionnaire and classified into inactive, light, and moderate/vigorous activity categories. Metabolic risk factors (dyslipidemia, type 2 diabetes mellitus, obesity, hypertension, inflammation, and insulin resistance) were categorized using clinical thresholds. After adjusting for basic confounders, engaging in light or moderate/vigorous physical activity was associated with a lower risk of CVD mortality (p activity remained at lower risk of CVD mortality. In addition, physical activity provided protective effects for CVD mortality in healthy subjects and those with metabolic risk factors in isolation or in clusters. In conclusion, physical activity was associated with a lower risk of CVD mortality independent of traditional and inflammatory risk factors. Taken together these results suggest that physical activity may protect against CVD mortality regardless of the presence of metabolic risk factors.

  13. Generation and functional characterization of a BCL10-inhibitory peptide that represses NF-kappaB activation.

    Science.gov (United States)

    Marasco, Daniela; Stilo, Romania; Sandomenico, Annamaria; Monti, Simona Maria; Tizzano, Barbara; de Capua, Antonia; Varricchio, Ettore; Liguoro, Domenico; Zotti, Tiziana; Formisano, Silvestro; Ruvo, Menotti; Vito, Pasquale

    2009-08-27

    The molecular complex containing BCL10 and CARMA [CARD (caspase recruitment domain)-containing MAGUK (membrane-associated guanylate kinase)] proteins has recently been identified as a key component in the signal transduction pathways that regulate activation of the transcription factor NF-kappaB (nuclear factor kappaB) in lymphoid and non-lymphoid cells. Assembly of complexes containing BCL10 and CARMA proteins relies on homophilic interactions established between the CARDs of these proteins. In order to identify BCL10-inhibitory peptides, we have established a method of assaying peptides derived from the CARD of BCL10 in binding competition assays of CARD-CARD self-association. By this procedure, a short peptide corresponding to amino acid residues 91-98 of BCL10 has been selected as an effective inhibitor of protein self-association. When tested in cell assays for its capacity to block NF-kappaB activation, this peptide represses activation of NF-kappaB mediated by BCL10, CARMA3 and PMA/ionomycin stimulation. Collectively, these results indicate that residues 91-98 of BCL10 are involved in BCL10 self-association and also participate in the interaction with external partners. We also show that blocking of the CARD of BCL10 may potentially be used for the treatment of pathological conditions associated with inappropriate NF-kappaB activation.

  14. Expression and Activation of STAT Transcription Factors in Breast Cancer

    Science.gov (United States)

    1998-05-08

    clinicians. J~, 273: 577-585, 1995. 183 Hundertmark 5, Buhler H, Rudolf M, Weitzel HK, Ragosch V: Inhibition of 11 beta-hydroxysteroid dehydrogenase...activated protein kinase through a Jakl-dependent pathway. Mol. Cell. Bioi., 17:3833-40, 1997. Stewart JF, Rubens RO, King RJ, Minton MJ, Steiner R

  15. Physical activity and cardiovascular risk factors in children

    DEFF Research Database (Denmark)

    Andersen, Lars Bo; Riddoch, Chris; Kriemler, Susi

    2011-01-01

    A number of recent systematic reviews have resulted in changes in international recommendations for children's participation in physical activity (PA) for health. The World Health Authority (WHO) has recently released new recommendations. The WHO still recommends 60 min of moderate to vigorous ph...

  16. No evidence for a putative involvement of platelet-activating factor in systemic lupus erythematosus without active nephritis

    Directory of Open Access Journals (Sweden)

    Yves Denizot

    2003-01-01

    Full Text Available Background: Platelet-activating factor (PAF seems to be implicated in systemic lupus erythematosus (SLE patients with associated renal diseases.Aims: In this study, we ensured the role of PAF in SLE patients without renal complications.

  17. Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.

    Science.gov (United States)

    Nishio, Y; Kashiwagi, A; Taki, H; Shinozaki, K; Maeno, Y; Kojima, H; Maegawa, H; Haneda, M; Hidaka, H; Yasuda, H; Horiike, K; Kikkawa, R

    1998-08-01

    Gene regulation in the cardiovascular tissues of diabetic subjects has been reported to be altered. To examine abnormal activities in transcription factors as a possible cause of this altered gene regulation, we studied the activity of two redox-sensitive transcription factors--nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1)--and the change in the mRNA content of heme oxygenase-1, which is regulated by these transcription factors in the cardiac tissues of rats with streptozotocin-induced diabetes. Increased activity of NF-kappaB and AP-1 but not nuclear transcription-activating factor, as determined by an electrophoretic mobility shift assay, was found in the hearts of 4-week diabetic rats. Glycemic control by a subcutaneous injection of insulin prevented these diabetes-induced changes in transcription factor activity. In accordance with these changes, the mRNA content of heme oxygenase-1 was increased fourfold in 4-week diabetic rats and threefold in 24-week diabetic rats as compared with control rats (P oxidative stress is involved in the activation of the transcription factors NF-kappaB and AP-1 in the cardiac tissues of diabetic rats, and that these abnormal activities of transcription factors could be associated with the altered gene regulation observed in the cardiovascular tissues of diabetic rats.

  18. Moderate to vigorous physical activity and sedentary time and cardiometabolic risk factors in children and adolescents

    DEFF Research Database (Denmark)

    Ekelund, Ulf; Luan, Jian'an; Sherar, Lauren B

    2012-01-01

    Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children.......Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children....

  19. Activating Transcription Factor 3 (ATF3 and the Nervous System

    Directory of Open Access Journals (Sweden)

    Patrick Norval Anderson

    2012-02-01

    Full Text Available It has been recognised for over a century that the ability of axons to regenerate in peripheral nerves is fundamentally greater than that of axons in the brain, spinal cord or optic nerves [early literature was reviewed in (Ramon y Cajal, 1928]. One factor that contributes to the successful regeneration of the axons in peripheral nerves is the complex cell body response the neurons show to axotomy. That transcription factors must play an important role in enabling neurons to regrow their axons is implicit to the observation that several hundred genes are regulated in neurons during axonal regeneration (Costigan et al., 2002; Boeshore et al., 2004. In addition, similarly large numbers of genes are regulated in the non-neuronal cells present in injured peripheral nerves [especially Schwann cells (Barrette et al., 2010] and CNS tissue. Of the transcription factors that regulate these changes in gene expression, the function of c-jun is best understood but ATF-3 (also known as LRF-1, LRG-21, CRG-5 and TI-241 is also upregulated in most of the neurons (Fig. 1 and Schwann cells that express c-jun. Indeed, ATF-3 has become a standard marker for neurons axotomised by peripheral nerve injury (Tsuzuki et al., 2001; Yamanaka et al., 2005; Yano et al., 2008; Linda et al., 2011 and its expression by injured neurons is closely correlated with a regenerative response. None the less, surprisingly little is known about the functions of ATF3 in neurons or glia within the injured nervous system, especially when compared with those of its potential binding partner, c-Jun.

  20. Factor B structure provides insights into activation of the central protease of the complement system

    NARCIS (Netherlands)

    Milder, F.J.; Gomes, L.; Schouten, A.; Janssen, B.J.C.; Huizinga, E.G.; Romijn, R.A.; Hemrika, W.; Roos, A; Daha, M.R.; Gros, P.

    2007-01-01

    Factor B is the central protease of the complement system of immune defense. Here, we present the crystal structure of human factor B at 2.3-A° resolution, which reveals how the five-domain proenzyme is kept securely inactive. The canonical activation helix of the Von Willebrand factor A (VWA) domai

  1. Role of HMW kininogen in surface-mediated activation of Factor XII.

    Science.gov (United States)

    Shimada, T; Sugo, T; Kato, H; Iwanaga, S

    1983-01-01

    We have shown that bovine HMW kininogen remarkably accelerates the activation of Factor XII and prekallikrein in the presence of kaolin, adsorbing on kaolin through the fragment 1.2 region and forming a complex with prekallikrein through the light chain region (Sugo et al., 1980; Ikari et al., 1981). The present study was undertaken to examine the role of HMW kininogen in the activation of Factor XII and prekallikrein with other negatively-charged surfaces. The activation system used here was as follows; (1) Activation of prekallikrein by Factor XII, (2) Activation of Factor XII by plasma kallikrein and (3) Activation of prekallikrein by Factor XIIa. Among a variety of foreign surfaces, amylose sulfate and sulfatide were the most efficient in the activation reaction of Factor XII and prekallikrein. Bovene HMW kininogen accelerated all the three reactions triggered by these surfaces. However, the accelerating effect of HMW kininogen on the activation of Factor XII by plasma kallikrein was very weak, when amylose sulfate or sulfatide was used as surface. The three reactions were highly dependent on the amounts of HMW kininogen and surfaces contained in the reaction mixtures. Excess amount of them inhibited these reactions. Among the various fragments, which were prepared from HMW kininogen digests with plasma and urinary kallikreins (Sugo et al., 1980), a large fragment consisting of fragment 1.2 and light chain accelerated the reactions. Thus both fragment 1.2 and the light chain region in HMW kininogen were essential for these activation reactions.

  2. THE TIME FACTOR IN MARITIME TRANSPORT AND PORT LOGISTICS ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Florin NICOLAE

    2016-06-01

    Full Text Available Execution of the carriage contract requires compliance to all the conditions in it, by all those involved in the transport. Main obligations incumbent upon the vessel, and obviously, to other transporters, who must provide transportation according to deadlines and safety. Contract compliance is certifying transport participants about their seriousness and an appropriate market quotation. Therefore, present work pragmatically sets schematics reference time associated implementation of the carriage contract. Also, are demonstrated relationships established between maritime transport “players” and sequence of activities related to the operation of the vessel in port. The authors propose a set of concepts and terms whose utility is established to solve practical problems in this area of activity.

  3. Are intestinal helminths risk factors for developing active tuberculosis?

    DEFF Research Database (Denmark)

    Elias, Daniel; Mengistu, Getahun; Akuffo, Hannah

    2006-01-01

    OBJECTIVES: To determine the prevalence of intestinal helminth infections in active tuberculosis patients and their healthy household contacts and to assess its association with active TB in an area endemic for both types of infections. METHODS: Smear-positive pulmonary TB patients and healthy...... household contacts were tested for intestinal helminths using direct microscopy and the formol-ether concentration techniques. Three consecutive stool samples were examined before the start of TB chemotherapy. Sputum microscopy was done using the sodium hypochlorite concentration techniques. Participants...... were also tested for HIV by commercial sandwich enzyme linked immunosorbent assay. RESULTS: The study population consisted of 230 smear-positive TB patients and 510 healthy household contacts. The prevalence of intestinal helminths was 71% in patients and 36% in controls. HIV seroprevalence...

  4. Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI

    Science.gov (United States)

    Puy, Cristina; Tucker, Erik I.; Ivanov, Ivan S.; Gailani, David; Smith, Stephanie A.; Morrissey, James H.; Gruber, András; McCarty, Owen J. T.

    2016-01-01

    Introduction Factor (F) XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa) promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα), in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP) derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin. Methods and Results Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma. Conclusions Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP. PMID:27764259

  5. Factors V and VII anticoagulant activities in the salivary glands of feeding Dermacentor andersoni ticks.

    Science.gov (United States)

    Gordon, J R; Allen, J R

    1991-02-01

    The salivary glands of Dermacentor andersoni ticks possess anticoagulant activities that can alter the clotting time of rabbit whole blood. Salivary gland extracts from female ticks inhibit both the intrinsic and extrinsic coagulation systems, and maximal activities against both pathways occur when the ticks attain about 250 mg feeding weight. These anticoagulants are directed against both coagulation factors V and VII, but they do not affect factors II or X. Despite this salivary anticoagulant activity, heavily tick-infested rabbits suffer no visible alteration of their peripheral blood coagulability and have no detectable circulating fibrin degradation products, suggesting that the ticks do not secrete a factor with fibrinolytic activity.

  6. Platelet-activating factor, tumor necrosis factor, hypoxia and necrotizing enterocolitis.

    Science.gov (United States)

    Hsueh, W; Caplan, M S; Sun, X; Tan, X; MacKendrick, W; Gonzalez-Crussi, F

    1994-01-01

    The pathogenesis of necrotizing enterocolitis (NEC) is poorly understood. We have established several animal models of NEC by using a combination of various stimuli and stress, including endotoxin, PAF, TNF, and hypoxia. We discuss the mechanism of their actions and the possible roles of these factors in the pathogenesis of human NEC.

  7. Physical activity, and physical activity related to sports, leisure and occupational activity as risk factors for ALS: A systematic review.

    Science.gov (United States)

    Lacorte, Eleonora; Ferrigno, Luigina; Leoncini, Emanuele; Corbo, Massimo; Boccia, Stefania; Vanacore, Nicola

    2016-07-01

    Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem neurodegenerative disease due to an interaction between environmental and genetic factors. This systematic review aims at gathering all available evidence on the association between physical activity (PA) and the risk of ALS. Relevant literature published up to January 2015 was gathered through structured searches on Medline, The Cochrane Library, and the ISI Web of Science databases. Studies considering any type of PA as the main exposure and a diagnosis of ALS or motor neuron disease were selected. Data were extracted in standardized forms, and the quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Bibliographic searches yielded 3168 records. Nineteen case control studies and 7 cohort studies met the inclusion criteria, and were included in the analysis. Evidence on cumulative measures of PA as a risk factor for ALS remain inconclusive. However, cohort studies report a significantly higher number of cases of ALS in professional soccer and American football players, and a slightly increased risk of ALS in varsity athletes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Giving children a voice: Exploring qualitative perspectives on factors influencing recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Schipperijn, Jasper; Tjørnhøj-Thomsen, Tine

    2017-01-01

    Facilitators and barriers to recess physical activity are not well understood. To date, research on recess physical activity has predominantly focused on quantitative measures typically focusing on a narrow set of predefined factors, often constructed by adults. To really understand the factors...... affecting recess physical activity it is crucial to observe and listen to children to know how they engage in and perceive recess physical activity. The aim of this paper was to gain knowledge on children’s perceptions and experiences of factors influencing their physical activity behaviour during recess...... 11–12-year-old children. The socio-ecological model was used as the overall theoretical framework. Twelve factors were identified as influencing the children’s recess physical activity: bodily self-esteem and ability; gender; gendered school culture; peer influence; conflicts and exclusion; space...

  9. The Drosophila Transcription Factors Tinman and Pannier Activate and Collaborate with Myocyte Enhancer Factor-2 to Promote Heart Cell Fate.

    Directory of Open Access Journals (Sweden)

    TyAnna L Lovato

    Full Text Available Expression of the MADS domain transcription factor Myocyte Enhancer Factor 2 (MEF2 is regulated by numerous and overlapping enhancers which tightly control its transcription in the mesoderm. To understand how Mef2 expression is controlled in the heart, we identified a late stage Mef2 cardiac enhancer that is active in all heart cells beginning at stage 14 of embryonic development. This enhancer is regulated by the NK-homeodomain transcription factor Tinman, and the GATA transcription factor Pannier through both direct and indirect interactions with the enhancer. Since Tinman, Pannier and MEF2 are evolutionarily conserved from Drosophila to vertebrates, and since their vertebrate homologs can convert mouse fibroblast cells to cardiomyocytes in different activator cocktails, we tested whether over-expression of these three factors in vivo could ectopically activate known cardiac marker genes. We found that mesodermal over-expression of Tinman and Pannier resulted in approximately 20% of embryos with ectopic Hand and Sulphonylurea receptor (Sur expression. By adding MEF2 alongside Tinman and Pannier, a dramatic expansion in the expression of Hand and Sur was observed in almost all embryos analyzed. Two additional cardiac markers were also expanded in their expression. Our results demonstrate the ability to initiate ectopic cardiac fate in vivo by the combination of only three members of the conserved Drosophila cardiac transcription network, and provide an opportunity for this genetic model system to be used to dissect the mechanisms of cardiac specification.

  10. [Risk factors in police activities: operational criticism in surveillance programs].

    Science.gov (United States)

    Ciprani, Fabrizio; Moroni, Maria; Conte, Giovanni

    2014-01-01

    The planning of specific health surveillance programs for police officers is extremely complex due to difficulty in predictability and variety of occupational hazards. Even in the case of conventional occupational risk factors clearly identified by current regulations, particular working conditions may require specific assessment to effectively identify and quantify the risk of occupational exposure. An extensive program of health surveillance, aimed at promoting overall health and effectiveness of the operators, would be really desirable, in order to help better address a number of risks that cannot be easily predicted. The progressive increase in the average age of the working population and the increasing prevalence of chronic degenerative diseases, may also suggest the need for health surveillance procedures designed to verify continued unqualified suitability to police service, providing for the identification of diversified suitability profiles in relation to age and state of health: accordingly, in regard to our field of interest, there is a close link between medico-legal eligibility and occupational medicine.

  11. THE FACTORS THAT INFLUENCE THE ACTIVITY OF ECONOMIC ENTITIES

    Directory of Open Access Journals (Sweden)

    SINTEA(ANGHEL LUCICA

    2014-02-01

    Full Text Available In the current situation many experts and ordinary people are asking themselves: Where is the economy heading? How can we counteract the disruptive factors? Which strategies must be employed? How should the risks be properly assessed in order to diminish them to the lowest level? What measures should be taken to improve the situation? This requires a necessary economic and financial analysis, based on the data from the financial statements, the discovery and application of risk assessment methods and the detection of procedures to mitigate this risk. It is also necessary to draw a comparison between the expected results of a rational and scientific research, and those obtained through empirical processes by means of marketing.

  12. [Family factors influence active commuting to school in Spanish children].

    Science.gov (United States)

    Rodríguez-López, Carlos; Villa-González, Emilio; Pérez-López, Isaac J; Delgado-Fernández, Manuel; Ruiz, Jonatan R; Chillón, Palma

    2013-01-01

    Introducción: El desplazamiento activo al colegio contribuye a aumentar los niveles de actividad física en niños. Los factores familiares pueden determinar dicho comportamiento. Objetivo: El objetivo fue analizar la asociación de la actividad laboral y el desplazamiento al trabajo de los padres con el modo de desplazamiento de sus hijos. Método: Participaron 721 familias de 4 colegios de la provincia de Granada. Las familias completaron un cuestionario sobre el modo de desplazamiento de sus hijos, la actividad laboral y el modo de desplazamiento de los padres, y la distancia y tiempo del trayecto al colegio de sus hijos. Las asociaciones entre la actividad laboral de las familias y modo de desplazamiento al trabajo con el desplazamiento activo al colegio de sus hijos se estudiaron con regresión logística binaria ajustando por distancia al colegio y edad de los hijos. Resultados: Los niños cuyos padres y madres no trabajaban eran más propensos a ir de forma activa al colegio que aquellos donde ambos trabajaban (p = 0,023; OR: 2,67; 95% IC: 1,14-6,23). Los niños cuyos padres y madres se desplazaban de forma activa al trabajo eran más propensos a ir de forma activa al colegio que aquellos donde ambos padres se desplazaban de forma pasiva al trabajo (p = 0,014; OR: 6,30; 95% IC: 1,45-27,26). Conclusión: Los factores familiares estaban relacionados con el modo de desplazamiento de los niños al colegio: en familias con desempleo y en familias con empleo donde los padres se desplazan al trabajo de forma activa, los hijos parecen ser más activos.

  13. WRKY Transcription Factors Involved in Activation of SA Biosynthesis Genes

    Directory of Open Access Journals (Sweden)

    Bol John F

    2011-05-01

    Full Text Available Abstract Background Increased defense against a variety of pathogens in plants is achieved through activation of a mechanism known as systemic acquired resistance (SAR. The broad-spectrum resistance brought about by SAR is mediated through salicylic acid (SA. An important step in SA biosynthesis in Arabidopsis is the conversion of chorismate to isochorismate through the action of isochorismate synthase, encoded by the ICS1 gene. Also AVRPPHB SUSCEPTIBLE 3 (PBS3 plays an important role in SA metabolism, as pbs3 mutants accumulate drastically reduced levels of SA-glucoside, a putative storage form of SA. Bioinformatics analysis previously performed by us identified WRKY28 and WRKY46 as possible regulators of ICS1 and PBS3. Results Expression studies with ICS1 promoter::β-glucuronidase (GUS genes in Arabidopsis thaliana protoplasts cotransfected with 35S::WRKY28 showed that over expression of WRKY28 resulted in a strong increase in GUS expression. Moreover, qRT-PCR analyses indicated that the endogenous ICS1 and PBS3 genes were highly expressed in protoplasts overexpressing WRKY28 or WRKY46, respectively. Electrophoretic mobility shift assays indentified potential WRKY28 binding sites in the ICS1 promoter, positioned -445 and -460 base pairs upstream of the transcription start site. Mutation of these sites in protoplast transactivation assays showed that these binding sites are functionally important for activation of the ICS1 promoter. Chromatin immunoprecipitation assays with haemagglutinin-epitope-tagged WRKY28 showed that the region of the ICS1 promoter containing the binding sites at -445 and -460 was highly enriched in the immunoprecipitated DNA. Conclusions The results obtained here confirm results from our multiple microarray co-expression analyses indicating that WRKY28 and WRKY46 are transcriptional activators of ICS1 and PBS3, respectively, and support this in silico screening as a powerful tool for identifying new components of stress

  14. Excretory-secretory products of Giardia lamblia induce interleukin-8 production in human colonic cells via activation of p38, ERK1/2, NF-κB and AP-1.

    Science.gov (United States)

    Lee, H-Y; Hyung, S; Lee, N Y; Yong, T-S; Han, S-H; Park, S-J

    2012-04-01

    Giardia lamblia, a pathogen causing diarrhoeal outbreaks, is interesting how it triggers immune response in the human epithelial cells. This study defined the crucial roles of signalling components involved in G. lamblia-induced cytokine production in human epithelial cells. Incubation of the gastrointestinal cell line HT-29 with G. lamblia GS trophozoites triggered production of interleukin (IL)-1β, IL-8 and tumour necrosis factor (TNF)-α. IL-8 production was not significantly decreased by physically separating the HT-29 cells and G. lamblia GS trophozoites. Indeed, treatment of HT-29 with G. lamblia excretory-secretory products (ESP) induced IL-8 production. Electrophoretic mobility gel shift and transfection assays using mutagenized IL-8 promoter reporter plasmids indicated that IL-8 production by G. lamblia ESP occurs through activation of two transcriptional factors, nuclear factor kappaB (NF-κB) and activator protein 1 (AP-1) in HT-29 cells. In addition, activation of two mitogen-activated protein kinases (MAPKs), p38 and ERK1/2, was also detected in the HT-29 cells stimulated with G. lamblia ESP. Selective inhibition of these MAPKs resulted in decreased production of ESP-induced IL-8. These results indicate that activation of p38, ERK1/2 MAPK, NF-κB and AP-1 comprises the signalling pathway responsible for IL-8 production by G. lamblia ESP.

  15. Activation of the Nuclear Factor E2-Related Factor 2/Antioxidant Response Element Pathway Is Neuroprotective after Spinal Cord Injury

    Science.gov (United States)

    Wang, Xiaoliang; de Rivero Vaccari, Juan Pablo; Wang, Handong; Diaz, Paulo; German, Ramon; Marcillo, Alex E.

    2012-01-01

    Abstract The activation of oxidative damage, neuroinflammation, and mitochondrial dysfunction has been implicated in secondary pathomechanisms following spinal cord injury (SCI). These pathophysiological processes lead to cell death and are tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. Here, we investigated whether activation of Nrf2/ARE is neuroprotective following SCI. Female Fischer rats were subjected to mild thoracic SCI (T8) using the New York University injury device. As early as 30 min after SCI, levels of Nrf2 transcription factor were increased in both nuclear and cytoplasmic fractions of neurons and astrocytes at the lesion site and remained elevated for 3 days. Treatment of injured rats with sulforaphane, an activator of Nrf2/ARE signaling, significantly increased levels of Nrf2 and glutamate-cysteine ligase (GCL), a rate-limiting enzyme for synthesis of glutathione, and decreased levels of inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) thus leading to a reduction in contusion volume and improvement in coordination. These results show that activation of the Nrf2/ARE pathway following SCI is neuroprotective and that sulforaphane is a viable compound for neurotherapeutic intervention in blocking pathomechanisms following SCI. PMID:21806470

  16. Activation of the nuclear factor E2-related factor 2/antioxidant response element pathway is neuroprotective after spinal cord injury.

    Science.gov (United States)

    Wang, Xiaoliang; de Rivero Vaccari, Juan Pablo; Wang, Handong; Diaz, Paulo; German, Ramon; Marcillo, Alex E; Keane, Robert W

    2012-03-20

    The activation of oxidative damage, neuroinflammation, and mitochondrial dysfunction has been implicated in secondary pathomechanisms following spinal cord injury (SCI). These pathophysiological processes lead to cell death and are tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. Here, we investigated whether activation of Nrf2/ARE is neuroprotective following SCI. Female Fischer rats were subjected to mild thoracic SCI (T8) using the New York University injury device. As early as 30 min after SCI, levels of Nrf2 transcription factor were increased in both nuclear and cytoplasmic fractions of neurons and astrocytes at the lesion site and remained elevated for 3 days. Treatment of injured rats with sulforaphane, an activator of Nrf2/ARE signaling, significantly increased levels of Nrf2 and glutamate-cysteine ligase (GCL), a rate-limiting enzyme for synthesis of glutathione, and decreased levels of inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) thus leading to a reduction in contusion volume and improvement in coordination. These results show that activation of the Nrf2/ARE pathway following SCI is neuroprotective and that sulforaphane is a viable compound for neurotherapeutic intervention in blocking pathomechanisms following SCI.

  17. Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity.

    Science.gov (United States)

    Jansen, Jan O; Scarpelini, Sandro; Pinto, Ruxandra; Tien, Homer C; Callum, Jeannie; Rizoli, Sandro B

    2011-11-01

    Recent studies have shown that acute traumatic coagulopathy is associated with hypoperfusion, increased plasma levels of soluble thrombomodulin, and decreased levels of protein C but with no change in factor VII activity. These findings led to the hypothesis that acute traumatic coagulopathy is primarily due to systemic anticoagulation, by activated protein C, rather than decreases in serine protease activity. This study was designed to examine the effect of hypoperfusion secondary to traumatic injury on the activity of coagulation factors. Post hoc analysis of prospectively collected data on severely injured adult trauma patients presenting to a single trauma center within 120 minutes of injury. Venous blood was analyzed for activity of factors II, V, VII, VIII, IX, X, and XI. Base deficit from arterial blood samples was used as a marker of hypoperfusion. Seventy-one patients were identified. The activity of factors II, V, VII, IX, X, and XI correlated negatively with base deficit, and after stratification into three groups, based on the severity of hypoperfusion, a statistically significant dose-related reduction in the activity of factors II, VII, IX, X, and XI was observed. Hypoperfusion is also associated with marked reductions in factor V activity levels, but these appear to be relatively independent of the degree of hypoperfusion. The activity of factor VIII did not correlate with base deficit. Hypoperfusion in trauma patients is associated with a moderate, dose-dependent reduction in the activity of coagulation factors II, VII, IX, X, and XI, and a more marked reduction in factor V activity, which is relatively independent of the severity of shock. These findings suggest that the mechanisms underlying decreased factor V activity--which could be due to activated protein C mediated cleavage, thus providing a possible link between the proposed thrombomodulin/thrombin-APC pathway and the serine proteases of the coagulation cascade--and the reductions in factors

  18. Specific features of domestic banks activity in the factoring services market

    OpenAIRE

    Trygub Olena V.

    2014-01-01

    The article analyses specific features of formation and development of the domestic factoring market. In the result of the study the article establishes that development of factoring in Ukraine took place due to active participation of banking institutions in this process and nowadays they are leaders in the domestic factoring services market due to possessing significant competitive advantages if compared with non-banking companies that specialise in factoring. The article detects that nowad...

  19. Specific features of domestic banks activity in the factoring services market

    Directory of Open Access Journals (Sweden)

    Trygub Olena V.

    2014-01-01

    Full Text Available The article analyses specific features of formation and development of the domestic factoring market. In the result of the study the article establishes that development of factoring in Ukraine took place due to active participation of banking institutions in this process and nowadays they are leaders in the domestic factoring services market due to possessing significant competitive advantages if compared with non-banking companies that specialise in factoring. The article detects that nowadays the banks are not only offerers of factoring services and finance factoring operations of other market participants, but also take an active part in establishment of factoring branches and are consumers of factoring services. In order to accelerate development of international factoring in Ukraine, the article offers such forms of state support of banks, which render factoring services to domestic exporters. The article recommends to focus banks’ attention, under modern conditions that are characterised with volatility of financial markets, on factoring servicing of those clients, whom they have long business relations with, without jeopardising themselves through provision of factoring services to a big number of small debtors. The article provides schemes of banks’ co-operation in the sphere of “non-classic” factoring with accredited factoring companies.

  20. Heat Shock Factor-1 and Nuclear Factor-kappaB Are Systemically Activated in Human Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Derek A O’Reilly

    2006-03-01

    Full Text Available Context :Nuclear factor-kappa B (NFkappaB is a transcription factor for a wide range of proinflammatory mediators while heat shock factor-1 (HSF-1 transcribes stress proteins that protect against cellular damage. Both are attractive therapeutic targets, undergoing investigation in other acute inflammatory conditions, such as sepsis. Objective :To evaluate the role of the transcription factors NF-kappaB and HSF-1 in human acute pancreatitis and their relationship to cytokine/chemokine production, disease severity and outcome. Patients :Twenty-four patients with acute pancreatitis and 12 healthy controls. Main outcome measures :Peripheral blood mononuclear cells were isolated. NF-kappaB and HSF-1 were measured by electrophoretic mobility shift assay. Soluble tumor necrosis factor (TNF receptor II and interleukin-8 were measured by ELISA. Acute physiology scores (APS, APACHE II scores and final Atlanta designations of severity were also determined. Results: Systemic NF-kappaB activation occurs in acute pancreatitis compared to healthy controls (P=0.004. However, there was no significant difference between those with mild and severe disease (P=0.685. Systemic activation of HSF-1 was observed in acute pancreatitis compared to healthy controls although this did not reach statistical significance (P=0.053. Activation, however, was greatest in those who had a final Atlanta designation of mild pancreatitis compared to those who had a severe attack of acute pancreatitis (P=0.036. Furthermore, HSF-1 was inversely correlated with acute physiology score (APS; r=-0.49, P=0.019 and APACHE II score (r=-0.47, P=0.026. Conclusions: Both NF-kappaB and HSF-1 are systemically activated in human acute pancreatitis. HSF-1 activation may protect against severity of pancreatitis

  1. Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts.

    LENUS (Irish Health Repository)

    Burke, J P

    2012-02-01

    BACKGROUND: Fibroblasts play a critical role in intestinal wound healing. Lipopolysaccharide (LPS) is a cell wall component of commensal gut bacteria. The effects of LPS on intestinal fibroblast activation were characterized. METHODS: Expression of the LPS receptor, toll-like receptor (TLR) 4, was assessed in cultured primary human intestinal fibroblasts using flow cytometry and confocal microscopy. Fibroblasts were treated with LPS and\\/or transforming growth factor (TGF) beta1. Nuclear factor kappaB (NFkappaB) pathway activation was assessed by inhibitory kappaBalpha (IkappaBalpha) degradation and NFkappaB promoter activity. Fibroblast contractility was measured using a fibroblast-populated collagen lattice. Smad-7, a negative regulator of TGF-beta1 signalling, and connective tissue growth factor (CTGF) expression were assessed using reverse transcriptase-polymerase chain reaction and western blot. The NFkappaB pathway was inhibited by IkappaBalpha transfection. RESULTS: TLR-4 was present on the surface of intestinal fibroblasts. LPS treatment of fibroblasts induced IkappaBalpha degradation, enhanced NFkappaB promoter activity and increased collagen contraction. Pretreatment with LPS (before TGF-beta1) significantly increased CTGF production relative to treatment with TGF-beta1 alone. LPS reduced whereas TGF-beta1 increased smad-7 expression. Transfection with an IkappaBalpha plasmid enhanced basal smad-7 expression. CONCLUSION: Intestinal fibroblasts express TLR-4 and respond to LPS by activating NFkappaB and inducing collagen contraction. LPS acts in concert with TGF-beta1 to induce CTGF. LPS reduces the expression of the TGF-beta1 inhibitor, smad-7.

  2. Inhibitory Effect of Memantine on Streptozotocin-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Neurotrophic Factor Decline in Astrocytes.

    Science.gov (United States)

    Rajasekar, N; Nath, Chandishwar; Hanif, Kashif; Shukla, Rakesh

    2016-12-01

    Our earlier studies showed that insulin receptor (IR) dysfunction along with neuroinflammation and amyloidogenesis played a major role in streptozotocin (STZ)-induced toxicity in astrocytes. N-methyl-D-aspartate (NMDA) receptor antagonist-memantine shows beneficial effects in Alzheimer's disease (AD) pathology. However, the protective molecular and cellular mechanism of memantine in astrocytes is not properly understood. Therefore, the present study was undertaken to investigate the effect of memantine on insulin receptors, neurotrophic factors, neuroinflammation, and amyloidogenesis in STZ-treated astrocytes. STZ (100 μM) treatment for 24 h in astrocytes resulted significant decrease in brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and insulin-degrading enzyme (IDE) expression in astrocytes. Treatment with memantine (1-10 μM) improved STZ-induced neurotrophic factor decline (BDNF, GDNF) along with IR dysfunction as evidenced by a significant increase in IR protein expression, phosphorylation of IRS-1, Akt, and GSK-3 α/β in astrocytes. Further, memantine attenuated STZ-induced amyloid precursor protein (APP), β-site APP-cleaving enzyme-1 and amyloid-β1-42 expression and restored IDE expression in astrocytes. In addition, memantine also displays protective effects against STZ-induced astrocyte activation showed by reduction of inflammatory markers, nuclear factor kappa-B translocation, glial fibrillary acidic protein, cyclooxygenase-2, tumor necrosis factor-α level, and oxidative-nitrostative stress. The results suggest that besides the NMDA receptor antagonisic activity, effect on astroglial IR and neurotrophic factor may also be an important factor in the beneficial effect of memantine in AD pathology. Graphical Abstract Novel neuroprotective mechanisms of memenatine in streptozotocin-induced toxicity in astrocytes.

  3. Vascular endothelial growth factor activities on osteoarthritic chondrocytes.

    Science.gov (United States)

    Pulsatelli, L; Dolzani, P; Silvestri, T; Frizziero, L; Facchini, A; Meliconi, R

    2005-01-01

    Evaluation of the role of VEGF in cartilage pathophysiology. VEGF release from chondrocytes in the presence of IL-1beta, TGFbeta and IL-10 was detected by immunoassay. VEGF receptor -1 and -2 expression and VEGF ability to modulate caspase -3 and cathepsin B expression were detected by immunohistochemistry on cartilage biopsies and cartilage explants. VEGF effects on chondrocyte proliferation was analysed by a fluorescent dye that binds nucleic acids. VEGF production by osteoartritis (OA) chondrocytes was significantly reduced by IL-1beta while it was increased in the presence of TGFbeta. Cartilage VEGFR-1 immunostaining was significantly downregulated in 'early' OA patients compared to normal controls (NC). VEGFR-2 expression was negligible both in OA and in NC. VEGF decreased the expression of caspase-3 and cathepsin B, whereas it did not affect proliferation. VEGF is able to down-modulate chondrocyte activities related to catabolic events involved in OA cartilage degradation.

  4. Transforming Growth Factor-β Signaling Pathway Activation in Keratoconus

    Science.gov (United States)

    ENGLER, CHRISTOPH; CHAKRAVARTI, SHUKTI; DOYLE, JEFFERSON; EBERHART, CHARLES G.; MENG, HUAN; STARK, WALTER J.; KELLIHER, CLARE; JUN, ALBERT S.

    2011-01-01

    PURPOSE To assess the presence of transforming growth factor-β (TGFβ) pathway markers in the epithelium of keratoconus patient corneas. DESIGN Retrospective, comparative case series of laboratory specimens. METHODS Immunohistochemistry results for TGFβ2, total TGFβ, mothers against decacentaplegic homolog (Smad) 2, and phosphorylated Smad2 was performed on formalin-fixed, paraffin-embedded sections of keratoconus patient corneas and normal corneas from human autopsy eyes. Keratoconus patient corneas were divided in two groups, depending on their severity based on keratometer readings and pachymetry. Autopsy controls were age-matched with the keratoconus cases. Immunohistochemistry signal quantification was performed using automated software. Real-time reverse-transcriptase polymerase chain reaction was performed on total ribonucleic acid of epithelium of keratoconus patient corneas and autopsy control corneas. RESULTS Immunohistochemistry quantification showed a significant increase in mean signal in the group of severe keratoconus cases compared with normal corneas for TGFβ2 and phosphorylated Smad2 (P keratoconus cases versus the autopsy controls. Reverse-transcriptase polymerase chain reaction exhibited elevated messenger ribonucleic acid levels of Smad2 and TGFβ2 in severe keratoconus corneal epithelium. CONCLUSIONS This work shows increased TGFβ pathway markers in severe keratoconus cases and provides the rationale for investigating TGFβ signaling further in the pathophysiology of keratoconus. PMID:21310385

  5. Protein kinase C{eta} activates NF-{kappa}B in response to camptothecin-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Raveh-Amit, Hadas; Hai, Naama; Rotem-Dai, Noa; Shahaf, Galit [The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev (Israel); Gopas, Jacob [The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev (Israel); The Department of Oncology, Soroka University Medical Center, Beer-Sheva 84105 (Israel); Livneh, Etta, E-mail: etta@bgu.ac.il [The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev (Israel)

    2011-08-26

    Highlights: {yields} Protein kinase C-eta (PKC{eta}) is an upstream regulator of the NF-{kappa}B signaling pathway. {yields} PKC{eta} activates NF-{kappa}B in non-stressed conditions and in response to DNA damage. {yields} PKC{eta} regulates NF-{kappa}B by activating I{kappa}B kinase (IKK) and inducing I{kappa}B degradation. -- Abstract: The nuclear factor {kappa}B (NF-{kappa}B) family of transcription factors participates in the regulation of genes involved in innate- and adaptive-immune responses, cell death and inflammation. The involvement of the Protein kinase C (PKC) family in the regulation of NF-{kappa}B in inflammation and immune-related signaling has been extensively studied. However, not much is known on the role of PKC in NF-{kappa}B regulation in response to DNA damage. Here we demonstrate for the first time that PKC-eta (PKC{eta}) regulates NF-{kappa}B upstream signaling by activating the I{kappa}B kinase (IKK) and the degradation of I{kappa}B. Furthermore, PKC{eta} enhances the nuclear translocation and transactivation of NF-{kappa}B under non-stressed conditions and in response to the anticancer drug camptothecin. We and others have previously shown that PKC{eta} confers protection against DNA damage-induced apoptosis. Our present study suggests that PKC{eta} is involved in NF-{kappa}B signaling leading to drug resistance.

  6. Activation of caspase 8 in the pituitaries of streptozotocin-induced diabetic rats: implication in increased apoptosis of lactotrophs.

    Science.gov (United States)

    Arroba, Ana I; Frago, Laura M; Argente, Jesús; Chowen, Julie A

    2005-10-01

    Lactotroph cell death is increased in streptozotocin-induced diabetic rats. To determine the mechanism involved, cell death proteins were accessed in pituitaries of diabetic (streptozotocin at 65 mg/kg, 2 months evolution) and control male rats by Western blot analysis and double immunohistochemistry. The intact and cleaved forms of caspase 9 were increased in diabetic rat pituitaries compared with controls. Although the proforms of caspases 3, 6, and 7 were increased in diabetic rat pituitaries, their activated forms were either unchanged or decreased. Activation of these effector caspases may be blocked by the increased expression of X-chromosome-linked inhibitor of apoptosis protein (XIAP) in diabetic rat pituitaries. However, in diabetic rats, XIAP expression in lactotrophs was decreased, suggesting that this cell type is not protected. Caspase 8, p53, and nuclear factor kappaB were more highly activated in diabetic rat pituitaries, with caspase 8 colocalization in lactotrophs being increased. These results suggest that, in the pituitaries of diabetic rats, the cascades of normal cell turnover are partially inhibited, possibly via XIAP, and this may be cell specific. Furthermore, activation of the extrinsic cell-death pathway, including activation of caspase 8, may underlie the diabetes-associated increase in lactotroph death.

  7. Expression of colony-stimulating factor 1 is associated with occurrence of osteochondral change in pigmented villonodular synovitis.

    Science.gov (United States)

    Ota, Takehiro; Urakawa, Hiroshi; Kozawa, Eiji; Ikuta, Kunihiro; Hamada, Shunsuke; Tsukushi, Satoshi; Shimoyama, Yoshie; Ishiguro, Naoki; Nishida, Yoshihiro

    2015-07-01

    Pigmented villonodular synovitis (PVNS) is a benign, translocation-derived neoplasm. Because of its high local recurrence rate after surgery and occurrence of osteochondral destruction, a novel therapeutic target is required. The present study aimed to evaluate the significance of protein expression possibly associated with the pathogenesis during the clinical course of PVNS. In 40 cases of PVNS, positivity of colony-stimulated factor 1 (CSF1), its receptor (CSF1R), and receptor activator of nuclear factor kappa-B ligand (RANKL) were immunohistochemically determined. The relationship between the positivity and clinical outcomes was investigated. High positivity of CSF1 staining intensity was associated with an increased incidence of osteochondral lesions (bone erosion and osteoarthritis) (p = 0.009), but not with the rate of local recurrence. Positivity of CSF1R and RANKL staining was not associated with any clinical variables. The number of giant cells was not correlated with positivity of any of the three proteins, or with the clinical outcome. Focusing on knee cases, CSF1 positivity was also associated with the incidence of osteochondal change (p = 0.02). CSF1R positivity was high in cases which had local recurrence, but not significantly so (p = 0.129). Determination of CSF1 and CSF1R expression may be useful as a prognosticator of the clinical course and/or outcomes of PVNS.

  8. Brain-derived neurotrophic factor and epidermal growth factor activate neuronal m-calpain via mitogen-activated protein kinase-dependent phosphorylation.

    Science.gov (United States)

    Zadran, Sohila; Jourdi, Hussam; Rostamiani, Karoline; Qin, Qingyu; Bi, Xiaoning; Baudry, Michel

    2010-01-20

    Calpain is a calcium-dependent protease that plays a significant role in synaptic plasticity, cell motility, and neurodegeneration. Two major calpain isoforms are present in brain, with mu-calpain (calpain1) requiring micromolar calcium concentrations for activation and m-calpain (calpain2) needing millimolar concentrations. Recent studies in fibroblasts indicate that epidermal growth factor (EGF) can activate m-calpain independently of calcium via mitogen-activated protein kinase (MAPK)-mediated phosphorylation. In neurons, MAPK is activated by both brain-derived neurotrophic factor (BDNF) and EGF. We therefore examined whether these growth factors could activate m-calpain by MAPK-dependent phosphorylation using cultured primary neurons and HEK-TrkB cells, both of which express BDNF and EGF receptors. Calpain activation was monitored by quantitative analysis of spectrin degradation and by a fluorescence resonance energy transfer (FRET)-based assay, which assessed the truncation of a calpain-specific peptide flanked by the FRET fluorophore pair DABCYL and EDANS. In both cell types, BDNF and EGF rapidly elicited calpain activation, which was completely blocked by MAPK and calpain inhibitors. BDNF stimulated m-calpain but not mu-calpain serine phosphorylation, an effect also blocked by MAPK inhibitors. Remarkably, BDNF- and EGF-induced calpain activation was preferentially localized in dendrites and dendritic spines of hippocampal neurons and was associated with actin polymerization, which was prevented by calpain inhibition. Our results indicate that, in cultured neurons, both BDNF and EGF activate m-calpain by MAPK-mediated phosphorylation. These results strongly support a role for calpain in synaptic plasticity and may explain why m-calpain, although widely expressed in CNS, requires nonphysiological calcium levels for activation.

  9. Factors Associated with High Levels of Physical Activity among Adults with Intellectual Disability

    Science.gov (United States)

    Temple, Viviene A.

    2009-01-01

    The aim was to identify factors associated with physical activity participation among active (i.e. more than or equal to 10 000 steps per day) individuals with intellectual disability. Staff at day program and supported employment organizations were asked to identify individuals they believed were physically active. To verify participants were…

  10. Factor VII-activating protease in patients with acute deep venous thrombosis

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Vitzthum, Frank; Funding, Eva;

    2008-01-01

    Factor VII-activating protease (FSAP) is involved in haemostasis and inflammation. FSAP cleaves single chain urokinase-type plasminogen activator (scu-PA). The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene leads to the expression of a FSAP variant with reduced ability to activate scu...

  11. T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis

    NARCIS (Netherlands)

    van Riemsdijk, I C; Baan, C C; Loonen, E H; Knoop, C J; Navarro Betonico, G; Niesters, H G; Zietse, R; Weimar, W

    2001-01-01

    BACKGROUND: The immunosuppressive state of hemodialysis (HD) patients is accompanied by activation of antigen-presenting cell-derived cytokines, for example, tumor necrosis factor-alpha (TNF-alpha), which are required for T-cell activation. To test whether an activated TNF-alpha system results in im

  12. Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity

    DEFF Research Database (Denmark)

    Sorensen, Anders B.; Madsen, Jesper Jonasson; Svensson, L. Anders;

    2016-01-01

    The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane-bound tissue factor (TF) initiates blood coagulation upon vascular injury. Binding of TF to FVIIa promotes allosteric conformational changes in the FVIIa protease domain and improves its catalytic propert...

  13. Cisplatin Induces Cytotoxicity through the Mitogen-Activated Protein Kinase Pathways ana Activating Transcription Factor 3

    Directory of Open Access Journals (Sweden)

    Carly St. Germain

    2010-07-01

    Full Text Available The mechanisms underlying the proapoptotic effect of the chemotherapeutic agent, cisplatin, are largely undefined. Understanding the mechanisms regulating cisplatin cytotoxicity may uncover strategies to enhance the efficacy of this important therapeutic agent. This study evaluates the role of activating transcription factor 3 (ATF3 as a mediator of cisplatin-induced cytotoxicity. Cytotoxic doses of cisplatin and carboplatin treatments consistently induced ATF3 expression in five tumor-derived cell lines. Characterization of this induction revealed a p53, BRCA1, and integrated stress response-independent mechanism, all previously implicated in stress-mediated ATF3 induction. Analysis of mitogenactivated protein kinase (MAPK pathway involvement in ATF3 induction by cisplatin revealed a MAPK-dependent mechanism. Cisplatin treatment combined with specific inhibitors to each MAPK pathway (c-Jun N-terminal kinase, extracellularsignal-regulated kinase, and p38 resulted in decreasedATF3 induction at the protein level. MAPK pathway inhibition led to decreased ATF3 messenger RNA expression and reduced cytotoxic effects of cisplatin as measured by the 3-(4,5-dimethylthiazol-2-ylF2,5-diphenyltetrazolium bromide cell viability assay. In A549 lung carcinoma cells, targeting ATF3 with specific small hairpin RNA also attenuated the cytotoxic effects of cisplatin. Similarly, ATF3-/murine embryonic fibroblasts (MEFs were shown to be less sensitive to cisplatin-induced cytotoxicity compared with ATF3+/+ MEFs. This study identifies cisplatin as a MAPK pathway-dependent inducer of ATF3, whose expression influences cisplatin’s cytotoxic effects.

  14. Predicting involvement in prison gang activity: street gang membership, social and psychological factors.

    Science.gov (United States)

    Wood, Jane L; Alleyne, Emma; Mozova, Katarina; James, Mark

    2014-06-01

    The aim of this study was to examine whether street gang membership, psychological factors, and social factors such as preprison experiences could predict young offenders' involvement in prison gang activity. Data were collected via individual interviews with 188 young offenders held in a Young Offenders Institution in the United Kingdom. Results showed that psychological factors such as the value individuals attached to social status, a social dominance orientation, and antiauthority attitudes were important in predicting young offenders' involvement in prison gang activity. Further important predictors included preimprisonment events such as levels of threat, levels of individual delinquency, and levels of involvement in group crime. Longer current sentences also predicted involvement in prison gang activity. However, street gang membership was not an important predictor of involvement in prison gang activity. These findings have implications for identifying prisoners involved in prison gang activity and for considering the role of psychological factors and group processes in gang research.

  15. Sexual activity and cardiac risk: is depression a contributing factor?

    Science.gov (United States)

    Roose, S P; Seidman, S N

    2000-07-20

    There is a well-documented association between depression, ischemic heart disease, and cardiovascular mortality. This association has a number of dimensions including: (1) depressed patients have a higher than expected rate of sudden cardiovascular death; (2) over the course of a lifetime, patients with depression develop symptomatic and fatal ischemic heart disease at a higher rate compared with a nondepressed group; and (3) depression after myocardial infarction (MI) is associated with increased cardiac mortality. Depression is also associated with sexual dysfunction, particularly erectile dysfunction. If depression is the primary illness, then erectile dysfunction can be considered a symptom of the depressive illness. However, if the erectile dysfunction is primary, men may develop a depressive syndrome in reaction to the loss of sexual function. Regardless of whether erectile dysfunction is a symptom of depression or depression is a consequence of erectile dysfunction, these conditions are frequently comorbid. Thus, the patient with ischemic heart disease who is depressed is more likely to have erectile difficulties. An attempt by this patient to engage in sexual activity is therefore more likely to be unsuccessful and, given the increase in cardiac mortality associated with depression, it may result in a serious cardiac event.

  16. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment

    Science.gov (United States)

    Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C -C; Cole, S W

    2016-01-01

    Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1–4 (EGR1–4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators. PMID:27187237

  17. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment.

    Science.gov (United States)

    Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C-C; Cole, S W

    2016-05-24

    Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1-4 (EGR1-4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators.

  18. Increasing Physical Activity Decreases Hepatic Fat and Metabolic Risk Factors.

    Science.gov (United States)

    Alderete, Tanya L; Gyllenhammer, Lauren E; Byrd-Williams, Courtney E; Spruijt-Metz, Donna; Goran, Michael I; Davis, Jaimie N

    2012-04-01

    This study assessed the changes in time spent in moderate to vigorous physical activity (MVPA) on fat depots, insulin action, and inflammation. Longitudinal data were generated from 66 Hispanic adolescents (15.6±1.1 yr; BMI percentile 97.1±3.0) who participated in a 16-wk nutrition or nutrition+exercise intervention. There were no effects of the intervention on PA, but there were inter-individual changes in PA. For purposes of this analysis, all intervention groups were combined to assess how changes in PA during 16 wk affected changes in adiposity, insulin action, and markers of inflammation. MVPA was assessed by 7-day accelerometry, total body fat via DXA, liver fat by MRI, and insulin, glucose and HOMA-IR via a fasting blood draw. A repeated measures ANCOVA was used to assess the effect of MVPA on fat depots, insulin action, and inflammatory markers. Sixty-two percent of participants increased MVPA (mean increase, 19.7±16.5 min/day) and 38% decreased MVPA (mean decrease, 10.7±10.1 min/day). Those who increased MVPA by as little as 20 min per day over 16 wk, compared to those who decreased MVPA, had significant reductions in liver fat (-13% vs. +3%; P=0.01), leptin levels (-18% vs. +4%; P=0.02), and fasting insulin (-23% vs. +5%; P=0.05). These findings indicate that a modest increase in MVPA can improve metabolic health in sedentary overweight Hispanic adolescents.

  19. The exonuclease ISG20 is directly induced by synthetic dsRNA via NF-kappaB and IRF1 activation.

    Science.gov (United States)

    Espert, Lucile; Rey, Clémence; Gonzalez, Laure; Degols, Geneviève; Chelbi-Alix, Mounira Kmar; Mechti, Nadir; Gongora, Céline

    2004-06-03

    Many interferon (IFN)-stimulated genes are also induced by double-stranded RNA (dsRNA), a component closely associated with the IFN system in the context of virus-host interactions. Recently, we demonstrated that the IFN-induced 3' --> 5' exonuclease ISG20 possesses antiviral activities against RNA viruses. Here we show that ISG20 induction by synthetic dsRNA (pIpC) is stronger and faster than its induction by IFN. Two families of transcription factors are implicated in the transcriptional activation of ISG20 by dsRNA. Initially, the NF-kappaB factors p50 and p65 bind and activate the kappaB element of the Isg20 promoter. This is followed by IRF1 binding to the ISRE. As pIpC often induces protein movements in the cells, we questioned whether it could influence ISG20 localization. Interestingly and contrary to IFN, dsRNA induces a nuclear matrix enrichment of the ISG20 protein. dsRNA induction of ISG20 via NF-kappaB and its antiviral activity led us to suggest that ISG20 could participate in the cellular response to virus infection.

  20. Systemic Injection of Low-Dose Lipopolysaccharide Fails to Break down the Blood–Brain Barrier or Activate the TLR4-MyD88 Pathway in Neonatal Rat Brain

    Directory of Open Access Journals (Sweden)

    Peng Wang

    2014-06-01

    Full Text Available We aimed to investigate whether peripheral low-dose lipopolysaccharide (LPS induces the breakdown of the blood–brain barrier (BBB and/or the activation of toll-like receptor 4 (TLR4 in the neonatal rat brain. Neonatal rats received intraperitoneal injections of low-dose LPS (0.3 mg/kg∙bw, and the BBB compromise was detected by Evans Blue extravasation and electron microscopy. Meanwhile, TLR4, adaptin myeloid differentiation factor 88 (MyD88, nuclear transcription factor kappa-B (NF-κB p50 and tumor necrosis factor alpha (TNFα in the neonatal rat brain were determined by quantitative real-time polymerase chain reaction (PCR and Western Blot. Immunohistochemistry was used to determine the distribution and activation of microglia in the brain after LPS administration. It was demonstrated that Evans Blue extravasation was not observed in the brain parenchyma, and that tight junctions of cerebral endothelial cells remained intact after systemic injections of LPS in neonatal rats. Although intracerebroventricular injections of LPS activated microglia and up-regulated the expression of TLR4, MyD88, NF-κB p50 and TNFα in the neonatal rat brain, systemic LPS did not induce these responses. These findings indicate that while the neonatal rat brain responds to the direct intra-cerebral administration of LPS through robust TLR4 activation, systemic low-dose LPS does not induce the innate immune reaction or compromise the BBB in neonatal rats.

  1. A correction factor to f-chart predictions of active solar fraction in active-passive heating systems

    Science.gov (United States)

    Evans, B. L.; Beckman, W. A.; Duffie, J. A.; Mitchell, J. W.; Klein, S. A.

    1983-11-01

    The extent to which a passive system degrades the performance of an active solar space heating system was investigated, and a correction factor to account for these interactions was developed. The transient system simulation program TRNSYS is used to simulate the hour-by-hour performance of combined active-passive (hybrid) space heating systems in order to compare the active system performance with simplified design method predictions. The TRNSYS simulations were compared to results obtained using the simplified design calculations of the f-Chart method. Comparisons of TRNSYS and f-Chart were used to establish the accuracy of the f-Charts for active systems. A correlation was then developed to correct the monthly loads input into the f-Chart method to account for controller deadbands in both hybrid and active only buildings. A general correction factor was generated to be applied to the f-Chart method to produce more accurate and useful results for hybrid systems.

  2. Plasma levels of plasminogen activator inhibitor type 1, factor VIII, prothrombin activation fragment 1+2, anticardiolipin, and antiprothrombin antibodies are risk factors for thrombosis in hemodialysis patients.

    Science.gov (United States)

    Molino, Daniela; De Santo, Natale G; Marotta, Rosa; Anastasio, Pietro; Mosavat, Mahrokh; De Lucia, Domenico

    2004-09-01

    Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non-systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition

  3. An increase in circulating B cell-activating factor in childhood-onset ocular myasthenia gravis.

    Science.gov (United States)

    Motobayashi, Mitsuo; Inaba, Yuji; Nishimura, Takafumi; Kobayashi, Norimoto; Nakazawa, Yozo; Koike, Kenichi

    2015-04-01

    Myasthenia gravis is a B cell-mediated autoimmune disorder. The pathophysiology of childhood-onset ocular myasthenia gravis remains unclear. We investigated serum B cell-activating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. Blood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B cell-activating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-γ; tumor necrosis factor-α) as well as the percentages of peripheral blood CD4+, CD8+, and CD19+ cells. Serum B cell-activating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B cell-activating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B cell-activating factor concentrations did not correlate with the percentages of CD4+, CD8+, and CD19+ cells or the CD4+/CD8+ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. Circulating B cell-activating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

    Science.gov (United States)

    Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

    2017-06-01

    During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation

  5. Intrapersonal, behavioral, and environmental factors associated with meeting recommended physical activity among rural Latino youth.

    Science.gov (United States)

    Perry, Cynthia K; Saelens, Brian E; Thompson, Beti

    2011-11-01

    This study aimed to identify intrapersonal, behavioral, and environmental factors associated with engaging in recommended levels of physical activity among rural Latino middle school youth. Data were from an anonymous survey of 773 Latino youth (51% female) about level of and barriers and motivators to physical activity, risk behaviors, and park use. Logistic regression models identified factors correlated with meeting recommended levels of physical activity (5 days or more 3 60 min/day). Thirty-four percent of girls and 41% of boys reported meeting this physical activity recommendation. Participation in an organized after school activity (p physical education (PE) classes 5 days a week (p physical activity level. Making PE available 5 days a week and creating opportunities for organized after school physical activity programs may increase the number of rural Latino middle school youth who meet recommended physical activity level.

  6. Distinct Roles for JNK and IKK Activation in Agouti-Related Peptide Neurons in the Development of Obesity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Eva Tsaousidou

    2014-11-01

    Full Text Available Activation of c-Jun N-terminal kinase 1 (JNK1- and inhibitor of nuclear factor kappa-B kinase 2 (IKK2-dependent signaling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. Here, we demonstrate that constitutive JNK activation in agouti-related peptide (AgRP-expressing neurons of the hypothalamus is sufficient to induce weight gain and adiposity in mice as a consequence of hyperphagia. JNK activation increases spontaneous action potential firing of AgRP cells and causes both neuronal and systemic leptin resistance. Similarly, activation of IKK2 signaling in AgRP neurons also increases firing of these cells but fails to cause obesity and leptin resistance. In contrast to JNK activation, IKK2 activation blunts insulin signaling in AgRP neurons and impairs systemic glucose homeostasis. Collectively, these experiments reveal both overlapping and nonredundant effects of JNK- and IKK-dependent signaling in AgRP neurons, which cooperate in the manifestation of the metabolic syndrome.

  7. Multiple factors confer specific Cdc42 and Rac protein activation by dedicator of cytokinesis (DOCK) nucleotide exchange factors.

    Science.gov (United States)

    Kulkarni, Kiran; Yang, Jing; Zhang, Ziguo; Barford, David

    2011-07-15

    DOCK (dedicator of cytokinesis) guanine nucleotide exchange factors (GEFs) activate the Rho-family GTPases Rac and Cdc42 to control cell migration, morphogenesis, and phagocytosis. The DOCK A and B subfamilies activate Rac, whereas the DOCK D subfamily activates Cdc42. Nucleotide exchange is catalyzed by a conserved DHR2 domain (DOCK(DHR2)). Although the molecular basis for DOCK(DHR2)-mediated GTPase activation has been elucidated through structures of a DOCK9(DHR2)-Cdc42 complex, the factors determining recognition of specific GTPases are unknown. To understand the molecular basis for DOCK-GTPase specificity, we have determined the crystal structure of DOCK2(DHR2) in complex with Rac1. DOCK2(DHR2) and DOCK9(DHR2) exhibit similar tertiary structures and homodimer interfaces and share a conserved GTPase-activating mechanism. Multiple structural differences between DOCK2(DHR2) and DOCK9(DHR2) account for their selectivity toward Rac1 and Cdc42. Key determinants of selectivity of Cdc42 and Rac for their cognate DOCK(DHR2) are a Phe or Trp residue within β3 (residue 56) and the ability of DOCK proteins to exploit differences in the GEF-induced conformational changes of switch 1 dependent on a divergent residue at position 27. DOCK proteins, therefore, differ from DH-PH GEFs that select their cognate GTPases through recognition of structural differences within the β2/β3 strands.

  8. High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Naghi Momeni

    2012-01-01

    Full Text Available Autism spectrum disorders (ASDs are neurodevelopmental and behavioural syndromes affecting social orientation, behaviour, and communication that can be classified as developmental disorders. ASD is also associated with immune system abnormality. Immune system abnormalities may be caused partly by complement system factor I deficiency. Complement factor I is a serine protease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system. Deficiency in factor I activity is associated with an increased incidence of infections in humans. In this paper, we show that the mean level of factor I activity in the ASD group is significantly higher than in the control group of typically developed and healthy children, suggesting that high activity of complement factor I might have an impact on the development of ASD.

  9. Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression.

    Science.gov (United States)

    Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression Exposure to many drugs and environmentally-relevant chemicals can cause adverse outcomes. These adverse outcomes, such as cancer, have been linked to mol...

  10. Factors Influencing the Introduction of Physical Activity Interventions in Primary Health Care: a Qualitative Study

    NARCIS (Netherlands)

    Huijg, J.M.; Zouwe, N. van der; Crone, M.R.; Verheijden, M.W.; Middelkoop, B.J.C.; Gebhardt, W.A.

    2015-01-01

    Background: The introduction of efficacious physical activity (PA) interventions in routine primary health care (PHC) is a complex process. Understanding factors influencing the process can enhance the development of successful introduction strategies. Purpose: The aim of this qualitative study was

  11. Children's perceptions of weight, obesity, nutrition, physical activity and related health and socio-behavioural factors

    National Research Council Canada - National Science Library

    Economos, Christina D; Bakun, Peter J; Herzog, Julia Bloom; Dolan, Peter R; Lynskey, Vanessa M; Markow, Dana; Sharma, Shanti; Nelson, Miriam E

    .... An online survey was conducted with children to capture their perceptions of weight, overweight, nutrition, physical activity and related socio-behavioural factors. Within the USA. US children (n 1224) aged 8-18 years...

  12. Effects of recombinant activated factor VII on coagulation measured by thromboelastography in liver transplantation

    NARCIS (Netherlands)

    Hendriks, HGD; Meijer, K; de Wolf, JTM; Porte, RJ; Klompmaker, IJ; Lip, H; Slooff, MJH; van der Meer, J

    Besides the conventional laboratory tests, thromboelastography (TEG) is used to monitor hemostasis during liver transplantation. A previous pilot study suggested a beneficial effect of recombinant activated factor VII (rFVIIa) on transfusion requirements in liver transplantation. In the present

  13. Factors associated with physical activity among young adults with a disability.

    Science.gov (United States)

    Saebu, M; Sørensen, M

    2011-10-01

    The purpose of this study was to examine: (1) total physical activity and (2) the relative importance of functioning and disability, environmental and personal factors for total physical activity among young adults with a disability. The International Classification of Functioning, Disability and Health developed by the World Health Organization was used as a structural framework for a cross-sectional survey, based on a questionnaire. The population studied was 327 young adults (age 18-30) with a disability who were members of interest organizations for persons with disabilities. Using an adapted version of the self-administered short form of International Physical Activity Questionnaire (IPAQ), the sample reported some differences in physical activity related to the type and the onset of disability. Linear regression analyses revealed that personal factors demonstrated more power in explaining the variance in physical activity than both the environmental factors and factors related to functioning and disability. As for the able-bodied, intrinsic motivation and identity as an active person were the factors most strongly associated with physical activity behavior. This should have important consequences for how professionals try to motivate people with disabilities for physical activity, and how they plan and implement rehabilitation.

  14. Identification of platelet-activating factor acetylhydrolase II in human skin.

    Science.gov (United States)

    Marques, Mariangela; Pei, Yong; Southall, Michael D; Johnston, John M; Arai, Hiroyuki; Aoki, Junken; Inoue, Takao; Seltmann, Holger; Zouboulis, Christos C; Travers, Jeffrey B

    2002-10-01

    Platelet-activating factor acetylhydrolases are a family of specialized phospholipase A2 enzymes. They serve an anti-inflammatory function by converting the proinflammatory autocoid, PAF, into biologically inactive lyso-PAF, by the removal of the sn-2 acetyl group of this glycerophospholipid. Similarly, platelet-activating factor acetylhydrolases can also degrade oxidatively modified sn-2 polyunsaturated-fatty-acid-containing phospholipids, which are toxic to cells. Platelet-activating factor acetylhydrolase II is a recently cloned member of this family of specialized phospholipases. Consistent with a potential role of this intracellular enzyme in protecting membrane phospholipids against oxidative stress, platelet-activating factor acetylhydrolase II has been shown to translocate from cytosol to membranes in response to pro-oxidative stressors, and overexpression of this enzyme decreases the cytotoxic effects of these agents. The objective of this study was to assess whether platelet-activating factor acetylhydrolase II is involved in protecting skin against oxidative stress. Platelet-activating factor acetylhydrolase II protein was demonstrated in human skin by immunohistochemistry, with the highest levels of the enzyme found in sebaceous glands and lesser amounts in epidermal keratinocytes. Treatment of epidermal cells with t-butylhydroperoxide or ultraviolet B radiation resulted in platelet-activating factor acetylhydrolase II translocation from cytosol to membranes. To assess the role of this enzyme in epidermal function, a recombinant retroviral strategy was used to overexpress platelet-activating factor acetylhydrolase II in the human keratinocyte-derived cell line HaCaT. Overexpression of platelet-activating factor acetylhydrolase II protected HaCaT cells against apop tosis induced by oxidative stressors t-butylhydroperoxide and ultraviolet B radiation. Similar levels of apoptosis, however, were seen in both control and platelet-activating-factor

  15. Dietary and Physical Activity/Inactivity Factors Associated with Obesity in School-Aged Children123

    OpenAIRE

    Perez-Rodriguez, Marcela; Melendez, Guillermo; Nieto, Claudia; Aranda, Marisol; Pfeffer, Frania

    2012-01-01

    Diet and physical activity (PA) are essential components of nutritional status. Adequate nutrition and an active lifestyle are key factors during childhood, because food habits track into adulthood. Children spend more time in school than in any other environment away from home. Studying the diet factors and patterns of PA that affect obesity risk in children during school hours and the complete school day can help identify opportunities to lower this risk. We directly measured the time child...

  16. Interferon regulatory factor 1 is required for mouse Gbp gene activation by gamma interferon.

    OpenAIRE

    1995-01-01

    Full-scale transcriptional activation of the mouse Gbp genes by gamma interferon (IFN-gamma) requires protein synthesis in embryonic fibroblasts. Although the Gbp-1 and Gbp-2 promoters contain binding sites for transcription factors Stat1 and IFN regulatory factor 1 (IRF-1), deletion analysis revealed that the Stat1 binding site is dispensable for IFN-gamma inducibility of Gbp promoter constructs in transfected fibroblasts. However, activation of the mouse Gbp promoter by IFN-gamma requires t...

  17. Giving children a voice: Exploring qualitative perspectives on factors influencing recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Schipperijn, Jasper; Tjørnhøj-Thomsen, Tine

    2017-01-01

    11–12-year-old children. The socio-ecological model was used as the overall theoretical framework. Twelve factors were identified as influencing the children’s recess physical activity: bodily self-esteem and ability; gender; gendered school culture; peer influence; conflicts and exclusion; space...... of actions addressing factors from different layers in the socio-ecological model to increase recess physical activity....

  18. Factors That Influence Exercise Among Adults With Arthritis in Three Activity Levels

    OpenAIRE

    Der Ananian, Cheryl; Wilcox, Sara; Saunders, Ruth; Watkins, Ken; Evans, Alexandra

    2006-01-01

    Introduction Recent public health objectives emphasize the importance of exercise for reducing disability among people with arthritis. Despite the documented benefits of exercise, people with arthritis are less active than those without arthritis. The purpose of this study was to examine the factors that influence exercise participation among insufficiently active individuals with arthritis and to compare these factors with those identified by nonexercisers and regular exercisers with arthrit...

  19. Role of platelet activating factor in pathogenesis of acute pancreatitis in rats.

    Science.gov (United States)

    Konturek, S J; Dembinski, A; Konturek, P J; Warzecha, Z; Jaworek, J; Gustaw, P; Tomaszewska, R; Stachura, J

    1992-01-01

    The importance of platelet activating factor in acute pancreatitis was examined by determining the tissue content of endogenous platelet activating factor and the protective effects of TCV-309, a highly selective platelet activating factor blocker, against caerulein induced pancreatitis in rats. Infusion of caerulein (10 micrograms/kg/h) for five hours resulted in about 70% increase in pancreatic weight, 22% rise in protein content, 50% reduction in tissue blood flow, nine fold increase in tissue level of platelet activating factor and 165% rise in plasma amylase as well as histological evidence of acute pancreatitis. Such infusion of caerulein in chronic pancreatic fistula rats caused a marked increase in protein output from basal secretion of 10 mg/30 minutes to 40 mg/30 minutes in the first hour of infusion followed by a decline in protein output to 15-20 mg/30 minutes in the following hours of the experiment. Exogenous platelet activating factor (50 micrograms/kg) injected ip produced similar alterations in weight, protein content, blood flow, and histology of the pancreas but the increment in serum amylase was significantly smaller and pancreatic secretion was reduced below the basal level. TCV-309 (50 micrograms/kg) given ip before caerulein or platelet activating factor administration significantly reduced the biochemical and morphological alterations caused by caerulein and abolished those induced by exogenous platelet activating factor. These results indicate that platelet activating factor plays an important role in the pathogenesis of acute pancreatitis probably by reducing the blood flow and increasing vascular permeability in the pancreas. PMID:1385272

  20. Hypoxia-Inducible Factor 1 Is an Inductor of Transcription Factor Activating Protein 2 Epsilon Expression during Chondrogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Stephan Niebler

    2015-01-01

    Full Text Available The transcription factor AP-2ε (activating enhancer-binding protein epsilon is expressed in cartilage of humans and mice. However, knowledge about regulatory mechanisms influencing AP-2ε expression is limited. Using quantitative real time PCR, we detected a significant increase in AP-2ε mRNA expression comparing initial and late stages of chondrogenic differentiation processes in vitro and in vivo. Interestingly, in these samples the expression pattern of the prominent hypoxia marker gene angiopoietin-like 4 (Angptl4 strongly correlated with that of AP-2ε suggesting that hypoxia might represent an external regulator of AP-2ε expression in mammals. In order to show this, experiments directly targeting the activity of hypoxia-inducible factor-1 (HIF1, the complex mediating responses to oxygen deprivation, were performed. While the HIF1-activating compounds 2,2′-dipyridyl and desferrioxamine resulted in significantly enhanced mRNA concentration of AP-2ε, siRNA against HIF1α led to a significantly reduced expression rate of AP-2ε. Additionally, we detected a significant upregulation of the AP-2ε mRNA level after oxygen deprivation. In sum, these different experimental approaches revealed a novel role for the HIF1 complex in the regulation of the AP-2ε gene in cartilaginous cells and underlined the important role of hypoxia as an important external regulatory stimulus during chondrogenic differentiation modulating the expression of downstream transcription factors.

  1. SOME IMPORTANT FACTORS AFFECTING EVOLUTION OF ACTIVITY BASED COSTING (ABC SYSTEM IN EGYPTIAN MANUFACTURING FIRMS

    Directory of Open Access Journals (Sweden)

    Karim MAMDOUH ABBAS

    2014-04-01

    Full Text Available The present investigation aims to determine the factors affecting evolution of Activity Based Costing (ABC system in Egyptian case. The study used the survey method to describe and analyze these factors in some Egyptian firms. The population of the study is Egyptian manufacturing firms. Accordingly, the number of received questionnaires was 392 (23 Egyptian manufacturing firms in the first half of 2013. Finally, the study stated some influencing factors for evolution this system (ABC in Egyptian manufacturing firms.

  2. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference...

  3. Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

    Science.gov (United States)

    Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

    2011-01-01

    Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

  4. Social Cognitive Factors Associated with Physical Activity in Elementary School Girls

    Science.gov (United States)

    Bean, Melanie K.; Miller, Sara; Mazzeo, Suzanne E.; Fries, Elizabeth A.

    2012-01-01

    Objective: To examine social cognitive factors associated with physical activity (PA) among preadolescent girls. Method: Social cognitive theory was used to examine PA in girls (N = 90; 71% African American) participating in Girls on the Run. Multiple regressions explored factors associated with PA at posttesting and 3-month follow-up. Results:…

  5. Root hair deformation activity of nodulation factor and their fate on Vicia sativa.

    NARCIS (Netherlands)

    Heidstra, R.; Geurts, R.; Franssen, H.; Spaink, H.P.; Kammen, van A.; Bisseling, T.

    1994-01-01

    We used a semiquantitative root hair deformation assay for Vicia sativa (vetch) to study the activity of Rhizobium leguminosarum bv viciae nodulation (Nod) factors. Five to 10 min of Nod factor-root interaction appears to be sufficient to induce root hair deformation. The first deformation is visibl

  6. Melissa officinalis Protects against Doxorubicin-Induced Cardiotoxicity in Rats and Potentiates Its Anticancer Activity on MCF-7 Cells.

    Science.gov (United States)

    Hamza, Alaaeldin Ahmed; Ahmed, Mahguob Mohamed; Elwey, Hanan Mohamed; Amin, Amr

    2016-01-01

    Cardiotoxicity is a limiting factor of doxorubicin (DOX)-based anticancer therapy. Due to its beneficial effects, we investigated whether standardized extract of Melissa officinalis (MO) can attenuate doxorubicin-induced cardiotoxicity and can potentiate the efficacy of DOX against human breast cancer cells. MO was administered orally to male albino rats once daily for 10 consecutive days at doses of 250, 500 and 750 mg/kg b.wt. DOX (15 mg/kg b.wt. i.p.) was administered on the 8th day. MO protected against DOX-induced leakage of cardiac enzymes and histopathological changes. MO ameliorated DOX-induced oxidative stress as evidenced by decreasing lipid peroxidation, protein oxidation and total oxidant capacity depletion and by increasing antioxidant capacity. Additionally, MO pretreatment inhibited inflammatory responses to DOX by decreasing the expressions of nuclear factor kappa-B, tumor necrosis factor-alpha and cyclooxygenase-2 and the activity of myeloperoxidase. MO ameliorated DOX-induced apoptotic tissue damage in heart of rats. In vitro study showed that MO augmented the anticancer efficacy of DOX in human breast cancer cells (MCF-7) and potentiated oxidative damage and apoptosis. Thus, combination of DOX and MO may prove future cancer treatment protocols safer and more efficient.

  7. Nuclear Factor-κB: Activation and Regulation during Toll-like Receptor Signaling

    Institute of Scientific and Technical Information of China (English)

    Ruaidhrí J. Carmody; Youhai H. Chen

    2007-01-01

    Toll-like receptors (TLRs) recognize distinct microbial components to initiate the innate and adaptive immune responses. TLR activation culminates in the expression of appropriate pro-inflammatory and immunomodulatory factors to meet pathogenic challenges. The transcription factor NF-κB is the master regulator of all TLR-induced responses and its activation is the pivotal event in TLR-mediated activation of the innate immune response. Many of the key molecular events required for TLR-induced NF-κB activation have been elucidated. However, much remain to be learned about the ability of TLRs to generate pathogen-specific responses using a limited number of transcription factors. This review will focus on our current understanding of NF-κB activation by TLRs and potential mechanisms for achieving a signal-specific response through NF-κB.

  8. Inferring yeast cell cycle regulators and interactions using transcription factor activities

    Directory of Open Access Journals (Sweden)

    Galbraith Simon J

    2005-06-01

    Full Text Available Abstract Background Since transcription factors are often regulated at the post-transcriptional level, their activities, rather than expression levels may provide valuable information for investigating functions and their interactions. The recently developed Network Component Analysis (NCA and its generalized form (gNCA provide a robust framework for deducing the transcription factor activities (TFAs from various types of DNA microarray data and transcription factor-gene connectivity. The goal of this work is to demonstrate the utility of TFAs in inferring transcription factor functions and interactions in Saccharomyces cerevisiae cell cycle regulation. Results Using gNCA, we determined 74 TFAs from both wild type and fkh1 fkh2 deletion mutant microarray data encompassing 1529 ORFs. We hypothesized that transcription factors participating in the cell cycle regulation exhibit cyclic activity profiles. This hypothesis was supported by the TFA profiles of known cell cycle factors and was used as a basis to uncover other potential cell cycle factors. By combining the results from both cluster analysis and periodicity analysis, we recovered nearly 90% of the known cell cycle regulators, and identified 5 putative cell cycle-related transcription factors (Dal81, Hap2, Hir2, Mss11, and Rlm1. In addition, by analyzing expression data from transcription factor knockout strains, we determined 3 verified (Ace2, Ndd1, and Swi5 and 4 putative interaction partners (Cha4, Hap2, Fhl1, and Rts2 of the forkhead transcription factors. Sensitivity of TFAs to connectivity errors was determined to provide confidence level of these predictions. Conclusion By subjecting TFA profiles to analyses based upon physiological signatures we were able to identify cell cycle related transcription factors consistent with current literature, transcription factors with potential cell cycle dependent roles, and interactions between transcription factors.

  9. Inhibition of the TEF/TEAD transcription factor activity by nuclear calcium and distinct kinase pathways.

    Science.gov (United States)

    Thompson, M; Andrade, V A; Andrade, S J; Pusl, T; Ortega, J M; Goes, A M; Leite, M F

    2003-02-07

    Transcription enhancer factor (TEF/TEAD) is a family of four transcription factors that share a common TEA-DNA binding domain and are involved in similar cellular functions, such as cell differentiation and proliferation. All adult tissues express at least one of the four TEAD genes, so this family of transcription factors may be of widespread importance, yet little is known about their regulation. Here we examine the factors that regulate TEAD activity in CHO cells. RT-PCR indicated the presence of TEAD-1, TEAD-3, and both isoforms of TEAD-4, but not TEAD-2. Quantitative measurements showed that TEAD-4 is most abundant, followed by TEAD-3, then TEAD-1. We examined the relative effects of nuclear and cytosolic Ca(2+) on TEAD activity, since TEAD proteins are localized to the nucleus and since free Ca(2+) within the nucleus selectively regulates transcription in some systems. Chelation of nuclear but not cytosolic Ca(2+) increased TEAD activity two times above control. Inhibition of mitogen-activated protein kinase (MAPK) also increased TEAD activity, while cAMP decreased TEAD activity, and protein kinase C had no effect. Together, these results show that nuclear Ca(2+), MAPK, and cAMP each negatively regulate the activity of the TEAD transcription factor.

  10. Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling.

    Science.gov (United States)

    Mutoh, Shingo; Sobhany, Mack; Moore, Rick; Perera, Lalith; Pedersen, Lee; Sueyoshi, Tatsuya; Negishi, Masahiko

    2013-05-07

    Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver. We found that phenobarbital activated CAR by inhibiting epidermal growth factor receptor (EGFR) signaling. Phenobarbital bound to EGFR and potently inhibited the binding of EGF, which prevented the activation of EGFR. This abrogation of EGFR signaling induced the dephosphorylation of receptor for activated C kinase 1 (RACK1) at Tyr(52), which then promoted the dephosphorylation of CAR at Thr(38) by the catalytic core subunit of protein phosphatase 2A. The findings demonstrated that the phenobarbital-induced mechanism of CAR dephosphorylation and activation is mediated through its direct interaction with and inhibition of EGFR.

  11. Comparing citrated native, kaolin-activated, and tissue factor-activated samples and determining intraindividual variability for feline thromboelastography.

    Science.gov (United States)

    Banerjee, Amrita; Blois, Shauna L; Wood, R Darren

    2011-11-01

    Thromboelastography (TEG) is a point-of-care whole blood test of hemostasis. While TEG is becoming more widely used in veterinary medicine, few studies describe the use of TEG in cats. The objectives of the current study were to: 1) document the range of TEG variables produced in healthy cats using 3 sample types (citrated native, kaolin-activated, and tissue factor-activated), and 2) determine if there was a significant difference between 2 separate samples obtained from individual healthy cats on the same day. Jugular venipuncture was performed in 20 cats, and citrated blood collected for TEG. TEG analysis was performed on citrated native, kaolin-activated, and tissue factor-activated blood for each sample. Two hours later, the procedure was repeated from the opposite jugular vein, yielding a total of 120 analyses. Reaction time (R), alpha angle (α), kappa value (κ), and maximum amplitude (MA) were recorded from each tracing. No significant differences were found between TEG tracings from the first and second venipuncture samples. Significant differences were found between sample types for R, α, κ, and MA. Means for citrated native/kaolin-activated/tissue factor-activated methods were R = 4.1/3.7/0.6 min; κ = 2.5/1.8/2.2 min; α = 59.9/65.1/70.4 degrees; MA = 47.4/49.9/44.7 mm. A limitation of this study was the small number of cats used. Thromboelastography analysis may be a suitable method of evaluating hemostasis in cats.

  12. Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

    Directory of Open Access Journals (Sweden)

    Herrera Maria

    2006-04-01

    Full Text Available Abstract Background Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG in vitro. Methods and results TG was quantified by time parameters: lag time (LT and time to peak (TTP, and by amount of TG: peak of TG (PTG and area under thrombin formation curve after 35 minutes (AUC→35min in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA, ADP, and collagen (Col. In addition, the effects of recombinant activated FVII (rFVIIa alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p 35min were significantly increased (p 35min (but not PTG when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. Conclusion Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis.

  13. Muscle Atrophy Reversed by Growth Factor Activation of Satellite Cells in a Mouse Muscle Atrophy Model

    DEFF Research Database (Denmark)

    Hauerslev, Simon; Vissing, John; Krag, Thomas O

    2014-01-01

    Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory...... factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth...... control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we...

  14. Comparison of Some Cardiovascular Risk Factors between Active and Sedentary Elderly Men

    Directory of Open Access Journals (Sweden)

    H. Najafgholizadeh

    2017-04-01

    Full Text Available Background: One of the major problems threatening the world’s people are cardiovascular diseases, accounting for 30% of the deaths. The factors exposing people to this danger are called risk factors. Objective: This study aimed to compare the cardiovascular risk factors and C-reactive protein between active and sedentary elderly men. Methods: The study was a descriptive comparison of two groups that were conducted in Rasht city in 2015. The subjects of this study consist of 30 active elderly men and 30 sedentary elderly men who were selected non-randomly and purposefully. Inclusion criteria of research for active subjects were have regular physical activity at least six months and don’t use cigarette and pills that affect profile lipids and inclusion criteria for sedentary subjects were don’t have regular physical activity and also don’t use cigarette and pills that affect profile lipids. The measured cardiovascular risk factors of subjects include fasting blood sugar (FBS, triglyceride (TG, total cholesterol (TC, highdensity lipoprotein (HDL, low-density lipoprotein (LDL, very low-density lipoprotein (VLDL, glycated haemoglobinA1c (HbA1c, and C-reactive protein (CRP. The statistical methods used for data analysis are Kolmogorov-Smirnov test, t-student, and U Mann-Whitney with significance level less than 0.05. Findings: The t-student exam shows that cardiovascular risk factors, including FBS, TG, TC, HDL, VLDL, HbA1c, and CRP, in active elderly men are lower than sedentary elderly men. This difference is also statistically significant (P≤0/01. Conclusion: The study showed that cardiovascular risk factors in active elderly men are less than sedentary ones. However, 80% of active elderly men had still at least one or several cardiovascular risk factors.

  15. Snoring, sympathetic activity and cardiovascular risk factors in a 70 year old population

    DEFF Research Database (Denmark)

    Jennum, P; Schultz-Larsen, K; Christensen, Niels Juel

    1993-01-01

    In order to describe the relation between snoring, cardiovascular risk factors, metabolic factors and sympathetitic activity, 804 70-year-old males and females were classified according to snoring habits and life-style factors (alcohol and tobacco consumption), blood pressure, body mass index (BMI....... Self-reported snoring was associated with gender (males showed higher prevalence than females, p ... with tobacco consumption (p = 0.08). No associations were found between snoring and fasting glucose, plasma lipids, plasma epinephrine or in the use of antihypertensive medication. In multivariate analysis, with forced entry of gender, BMI, physical activity, alcohol and tobacco consumption, the relation...

  16. Factors Involved in Iranian Women Heads of Household's Health Promotion Activities: A Grounded Theory Study.

    Science.gov (United States)

    Rafii, Forough; Seyedfatemi, Naima; Rezaei, Mahboubeh

    2013-01-01

    We aimed to explore and describe the factors involved in Iranian women heads of household's health promotion activities. Grounded theory was used as the method. Sixteen women heads of household were recruited. Data were generated by semi structured interviews. Our findings indicated that remainder of resources (money, time and energy) alongside perceived severity of health risk were two main factors whereas women's personal and socio-economic characteristics were two contextual factors involved in these women's health promotion activities. To help these women improve their health status, we recommended that the government, non-governmental organizations and health care professionals provide them with required resources and increase their knowledge by holding training sessions.

  17. Hemorrhage induces rapid in vivo activation of CREB and NF-kappaB in murine intraparenchymal lung mononuclear cells.

    Science.gov (United States)

    Shenkar, R; Abraham, E

    1997-02-01

    Increased expression of proinflammatory cytokines appears to be an important factor contributing to the development of acute lung injury. In murine models, mRNA levels of proinflammatory and immunoregulatory cytokines, including IL-1alpha, IL-1beta, TGF-beta1, and TNF-alpha, are increased in intraparenchymal lung mononuclear cells 1 h after hemorrhage. Binding elements for the nuclear transcriptional regulatory factors, nuclear factor kappaB (NF-kappaB), CCAAT/enhancer binding protein beta (C/EBPbeta), serum protein 1 (Sp1), activator protein 1 (AP-1), and the cyclic AMP response-element binding protein (CREB) are present in the promoter regions of numerous cytokine genes, including those whose expression is increased after blood loss. To investigate early transcriptional mechanisms which may be involved in regulating pulmonary cytokine expression after hemorrhage, we examined in vivo activation of these five nuclear transcriptional factors among intraparenchymal lung mononuclear cells obtained in the immediate post-hemorrhage period. Activation of NF-kappaB and CREB, but not C/EBPbeta, Sp1, or AP-1, was present in lung mononuclear cells isolated from mice 15 min after hemorrhage. Inhibition of xanthine oxidase by prior feeding with either an allopurinol-supplemented or a tungsten-enriched diet prevented hemorrhage-induced activation of CREB, but not NF-kappaB. These results demonstrate that hemorrhage leads to rapid in vivo activation in the lung of CREB through a xanthine oxidase-dependent mechanism and of NF-kappaB through other pathways, and suggest that the activation of these transcriptional factors may have an important role in regulating pulmonary cytokine expression and the development of acute lung injury after blood loss.

  18. Testing the Youth Physical Activity Promotion Model: Fatness and Fitness as Enabling Factors

    Science.gov (United States)

    Chen, Senlin; Welk, Gregory J.; Joens-Matre, Roxane R.

    2014-01-01

    As the prevalence of childhood obesity increases, it is important to examine possible differences in psychosocial correlates of physical activity between normal weight and overweight children. The study examined fatness (weight status) and (aerobic) fitness as Enabling factors related to youth physical activity within the Youth Physical Activity…

  19. Factors of physical activity among Chinese children and adolescents : A systematic review

    NARCIS (Netherlands)

    Lu, Congchao; Stolk, Ronald P.; Sauer, Pieter J. J.; Sijtsma, Anna; Wiersma, Rikstje; Huang, Guowei; Corpeleijn, Eva

    2017-01-01

    Background: Lack of physical activity is a growing problem in China, due to the fast economic development and changing living environment over the past two decades. The aim of this review is to summarize the factors related to physical activity in Chinese children and adolescents during this

  20. PAK1 negatively regulates the activity of the Rho exchange factor NET1.

    Science.gov (United States)

    Alberts, Arthur S; Qin, Huajun; Carr, Heather S; Frost, Jeffrey A

    2005-04-01

    Rho family small G-protein activity is controlled by guanine nucleotide exchange factors that stimulate the release of GDP, thus allowing GTP binding. Once activated, Rho proteins control cell signaling through interactions with downstream effector proteins, leading to changes in cytoskeletal organization and gene expression. The ability of Rho family members to modulate the activity of other Rho proteins is also intrinsic to these processes. In this work we show that the Rac/Cdc42hs-regulated protein kinase PAK1 down-regulates the activity of the RhoA-specific guanine nucleotide exchange factor NET1. Specifically, PAK1 phosphorylates NET1 on three sites in vitro: serines 152, 153, and 538. Replacement of serines 152 and 153 with glutamate residues down-regulates the activity of NET1 as an exchange factor in vitro and its ability to stimulate actin stress fiber formation in cells. Using a phospho-specific antibody that recognizes NET1 phosphorylated on serine 152, we show that PAK1 phosphorylates NET1 on this site in cells and that Rac1 stimulates serine 152 phosphorylation in a PAK1-dependent manner. Furthermore, coexpression of constitutively active PAK1 inhibits the ability of NET1 to stimulate actin polymerization only when serines 152 and 153 are present. These data provide a novel mechanism for the control of RhoA activity by Rac1 through the PAK-dependent phosphorylation of NET1 to reduce its activity as a guanine nucleotide exchange factor.

  1. Testing the Youth Physical Activity Promotion Model: Fatness and Fitness as Enabling Factors

    Science.gov (United States)

    Chen, Senlin; Welk, Gregory J.; Joens-Matre, Roxane R.

    2014-01-01

    As the prevalence of childhood obesity increases, it is important to examine possible differences in psychosocial correlates of physical activity between normal weight and overweight children. The study examined fatness (weight status) and (aerobic) fitness as Enabling factors related to youth physical activity within the Youth Physical Activity…

  2. Factors that Limit and Enable Preschool-Aged Children's Physical Activity on Child Care Centre Playgrounds

    Science.gov (United States)

    Coleman, Bianca; Dyment, Janet E.

    2013-01-01

    The incidence of childhood obesity amongst preschool-aged children has increased dramatically in recent years and can be attributed, in part, to a lack of physical activity amongst children in this age group. This study explores the social factors that stand to limit and/or enable children's physical activity opportunities in outdoor settings in…

  3. Association between Social and Environmental Factors and Physical Activity Opportunities in Middle Schools

    Science.gov (United States)

    Xu, Furong; Chepyator-Thomson, Jepkorir; Liu, Wenhao; Schmidlein, Robert

    2010-01-01

    School-based physical activity (PA) interventions impact children's PA involvement and thus opportunities and associated factors for the promotion of physical activity in children need to be examined. The purpose of this study was to examine physical education teachers' perceptions of PA opportunities available to students at the middle school…

  4. Physical and Psychosocial Factors Associated With Physical Activity in Patients With Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    Hartman, Jorine E.; Boezen, H. Marike; de Greef, Mathieu H.; ten Hacken, Nick H.

    2013-01-01

    Objectives: To assess physical activity and sitting time in patients with chronic obstructive pulmonary disease (COPD) and to investigate which physical and psychosocial factors are associated with physical activity and sitting time. Design: Cross-sectional study. Setting: Patients were recruited at

  5. Platelet-activating factor acetylhydrolase and haemophagocytosis in the sepsis syndrome

    Directory of Open Access Journals (Sweden)

    Franck Trimoreau

    2000-01-01

    Full Text Available Sepsis syndrome (SS is associated with depressed PAF acetylhydrolase, the enzyme responsible for the degradation of platelet activating factor. PAF acetylhydrolase is in a large part produced by macrophages, whose inadequate activation with haemophagocytosis is frequent in patients with SS.

  6. Tead proteins activate the Foxa2 enhancer in the node in cooperation with a second factor.

    Science.gov (United States)

    Sawada, Atsushi; Nishizaki, Yuriko; Sato, Hiroko; Yada, Yukari; Nakayama, Rika; Yamamoto, Shinji; Nishioka, Noriyuki; Kondoh, Hisato; Sasaki, Hiroshi

    2005-11-01

    The cell population and the activity of the organizer change during the course of development. We addressed the mechanism of mouse node development via an analysis of the node/notochord enhancer (NE) of Foxa2. We first identified the core element (CE) of the enhancer, which in multimeric form drives gene expression in the node. The CE was activated in Wnt/beta-catenin-treated P19 cells with a time lag, and this activation was dependent on two separate sequence motifs within the CE. These same motifs were also required for enhancer activity in transgenic embryos. We identified the Tead family of transcription factors as binding proteins for the 3' motif. Teads and their co-factor YAP65 activated the CE in P19 cells, and binding of Tead to CE was essential for enhancer activity. Inhibition of Tead activity by repressor-modified Tead compromised NE enhancer activation and notochord development in transgenic mouse embryos. Furthermore, manipulation of Tead activity in zebrafish embryos led to altered expression of foxa2 in the embryonic shield. These results suggest that Tead activates the Foxa2 enhancer core element in the mouse node in cooperation with a second factor that binds to the 5' element, and that a similar mechanism also operates in the zebrafish shield.

  7. Streptococcus pyogenes CAMP factor attenuates phagocytic activity of RAW 264.7 cells.

    Science.gov (United States)

    Kurosawa, Mie; Oda, Masataka; Domon, Hisanori; Saitoh, Issei; Hayasaki, Haruaki; Terao, Yutaka

    2016-02-01

    Streptococcus pyogenes produces molecules that inhibit the function of human immune system, thus allowing the pathogen to grow and spread in tissues. It is known that S. pyogenes CAMP factor increases erythrocytosis induced by Staphylococcus aureus β-hemolysin. However, the effects of CAMP factor for immune cells are unclear. In this study, we investigated the effects of CAMP factor to macrophages. Western blotting analysis demonstrated that all examined strains expressed CAMP factor protein. In the presence of calcium or magnesium ion, CAMP factor was significantly released in the supernatant. In addition, both culture supernatant from S. pyogenes strain SSI-9 and recombinant CAMP factor dose-dependently induced vacuolation in RAW 264.7 cells, but the culture supernatant from Δcfa isogenic mutant strain did not. CAMP factor formed oligomers in RAW 264.7 cells in a time-dependent manner. CAMP factor suppressed cell proliferation via G2 phase cell cycle arrest without inducing cell death. Furthermore, CAMP factor reduced the uptake of S. pyogenes and phagocytic activity indicator by RAW 264.7 cells. These results suggest that CAMP factor works as a macrophage dysfunction factor. Therefore, we conclude that CAMP factor allows S. pyogenes to escape the host immune system, and contribute to the spread of streptococcal infection.

  8. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

    Directory of Open Access Journals (Sweden)

    A. Zembron-Lacny

    2016-01-01

    Full Text Available Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF and its relationship to oxidative damage and conventional cardiovascular disease (CVD biomarkers, such as atherogenic index, C-reactive protein (hsCRP and oxidized LDL (oxLDL, in active and inactive men. Seventeen elderly males (61-80 years and 17 young males (20-24 years participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001. In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL, hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men.

  9. The stress signalling pathway nuclear factor E2-related factor 2 is activated in the liver of sows during lactation

    Directory of Open Access Journals (Sweden)

    Rosenbaum Susann

    2012-10-01

    Full Text Available Abstract Background It has recently been shown that the lactation-induced inflammatory state in the liver of dairy cows is accompanied by activation of the nuclear factor E2-related factor 2 (Nrf2 pathway, which regulates the expression of antioxidant and cytoprotective genes and thereby protects tissues from inflammatory mediators and reactive oxygen species (ROS. The present study aimed to study whether the Nrf2 pathway is activated also in the liver of lactating sows. Findings Transcript levels of known Nrf2 target genes, UGT1A1 (encoding glucuronosyltransferase 1 family, polypeptide A1, HO-1 (encoding heme oxygenase 1, NQO1 (encoding NAD(PH dehydrogenase, quinone 1, GPX1 (encoding glutathione peroxidase, PRDX6 (encoding peroxiredoxin 6, TXNRD1 (encoding thioredoxin reductase 1, and SOD (encoding superoxide dismutase, in the liver are significantly elevated (between 1.7 and 3.1 fold in lactating sows compared to non-lactating sows. The inflammatory state in the liver was evidenced by the finding that transcript levels of genes encoding acute phase proteins, namely haptoglobin (HP, fibrinogen γ (FGG, complement factor B (CFB, C-reactive protein (CRP and lipopolysaccharide-binding protein (LBP, were significantly higher (2 to 8.7 fold in lactating compared to non-lactating sows. Conclusions The results of the present study indicate that the Nrf2 pathway in the liver of sows is activated during lactation. The activation of Nrf2 pathway during lactation in sows might be interpreted as a physiologic means to counteract the inflammatory process and to protect the liver against damage induced by inflammatory signals and ROS.

  10. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.

    Science.gov (United States)

    Fu, Hongxia; Jiang, Yan; Yang, Darren; Scheiflinger, Friedrich; Wong, Wesley P; Springer, Timothy A

    2017-08-23

    Von Willebrand factor, an ultralarge concatemeric blood protein, must bind to platelet GPIbα during bleeding to mediate hemostasis, but not in the normal circulation to avoid thrombosis. Von Willebrand factor is proposed to be mechanically activated by flow, but the mechanism remains unclear. Using microfluidics with single-molecule imaging, we simultaneously monitored reversible Von Willebrand factor extension and binding to GPIbα under flow. We show that Von Willebrand factor is activated through a two-step conformational transition: first, elongation from compact to linear form, and subsequently, a tension-dependent local transition to a state with high affinity for GPIbα. High-affinity sites develop only in upstream regions of VWF where tension exceeds ~21 pN and depend upon electrostatic interactions. Re-compaction of Von Willebrand factor is accelerated by intramolecular interactions and increases GPIbα dissociation rate. This mechanism enables VWF to be locally activated by hydrodynamic force in hemorrhage and rapidly deactivated downstream, providing a paradigm for hierarchical mechano-regulation of receptor-ligand binding.Von Willebrand factor (VWF) is a blood protein involved in clotting and is proposed to be activated by flow, but the mechanism is unknown. Here the authors show that VWF is first converted from a compact to linear form by flow, and is subsequently activated to bind GPIbα in a tension-dependent manner.

  11. Objectively measured physical activity in Brazilians with visual impairment: description and associated factors.

    Science.gov (United States)

    Barbosa Porcellis da Silva, Rafael; Marques, Alexandre Carriconde; Reichert, Felipe Fossati

    2017-05-19

    Low level of physical activity is a serious health issue in individuals with visual impairment. Few studies have objectively measured physical activity in this population group, particularly outside high-income countries. The aim of this study was to describe physical activity measured by accelerometry and its associated factors in Brazilian adults with visual impairment. In a cross-sectional design, 90 adults (18-95 years old) answered a questionnaire and wore an accelerometer for at least 3 days (including one weekend day) to measure physical activity (min/day). Sixty percent of the individuals practiced at least 30 min/day of moderate-to-vigorous physical activity. Individuals who were blind were less active, spent more time in sedentary activities and spent less time in moderate and vigorous activities than those with low vision. Individuals who walked mainly without any assistance were more active, spent less time in sedentary activities and spent more time in light and moderate activities than those who walked with a long cane or sighted guide. Our data highlight factors associated with lower levels of physical activity in people with visual impairment. These factors, such as being blind and walking without assistance should be tackled in interventions to increase physical activity levels among visual impairment individuals. Implications for Rehabilitation Physical inactivity worldwide is a serious health issue in people with visual impairments and specialized institutions and public policies must work to increase physical activity level of this population. Those with lower visual acuity and walking with any aid are at a higher risk of having low levels of physical activity. The association between visual response profile, living for less than 11 years with visual impairment and PA levels deserves further investigations Findings of the present study provide reliable data to support rehabilitation programs, observing the need of taking special attention to

  12. Change of Coagulation Factor Ⅷ and Antithrombin Ⅲ Activity in Bank-Stored Blood

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd day, and 70 % of the activity at the 7th day. FⅧ:c showed no obvious change after 24 h, until the 3rd day. It lost 40 %-60 % of the activity after 36 h and was reduced to the 30 % of the original activity at the 5th day. Our results suggested that at the 3rd day coagulation factor Ⅷ of bank-stored blood can be used to replenish antithrombin Ⅲ, while bank-stored blood in one day can be used to replenish FⅧ.

  13. Krüppel-like factor 4, a novel transcription factor regulates microglial activation and subsequent neuroinflammation

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    Das Sulagna

    2010-10-01

    Full Text Available Abstract Background Activation of microglia, the resident macrophages of the central nervous system (CNS, is the hallmark of neuroinflammation in neurodegenerative diseases and other pathological conditions associated with CNS infection. The activation of microglia is often associated with bystander neuronal death. Nuclear factor-κB (NF-κB is one of the important transcription factors known to be associated with microglial activation which upregulates the expression of inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (Cox-2 and other pro-inflammatory cytokines. Recent studies have focused on the role of Krüppel-like factor 4 (Klf4, one of the zinc-finger transcription factors, in mediating inflammation. However, these studies were limited to peripheral system and its role in CNS is not understood. Our studies focused on the possible role of Klf4 in mediating CNS inflammation. Methods For in vitro studies, mouse microglial BV-2 cell lines were treated with 500 ng/ml Salmonella enterica lipopolysacchride (LPS. Brain tissues were isolated from BALB/c mice administered with 5 mg/kg body weight of LPS. Expressions of Klf4, Cox-2, iNOS and pNF-κB were evaluated using western blotting, quantitative real time PCR, and reverse transcriptase polymerase chain reactions (RT-PCRs. Klf4 knockdown was carried out using SiRNA specific for Klf4 mRNA and luciferase assays and electromobility shift assay (EMSA were performed to study the interaction of Klf4 to iNOS promoter elements in vitro. Co-immunoprecipitation of Klf4 and pNF-κB was done in order to study a possible interaction between the two transcription factors. Results LPS stimulation increased Klf4 expression in microglial cells in a time- and dose-dependent manner. Knockdown of Klf4 resulted in decreased levels of the pro-inflammatory cytokines TNF-α, MCP-1 and IL-6, along with a significant decrease in iNOS and Cox-2 expression. NO production also decreased as a result of Klf4 knockdown

  14. Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Ankylosing Spondylitis.

    Directory of Open Access Journals (Sweden)

    Inês P Perpétuo

    Full Text Available Ankylosing Spondylitis (AS is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi have ongoing local bone formation. The aim of this study was to assess the effect of TNFi in the differentiation and activity of osteoclasts (OC in AS patients.13 AS patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 25 healthy donors were recruited as controls. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and qRT-PCR for OC specific genes were performed.RANKL+ circulating lymphocytes (B and T cells and IL-17A, IL-23 and TGF-β levels were decreased after TNFi treatment. We found no differences in the frequency of the different monocyte subpopulations, however, we found decreased expression of CCR2 and increased expression of CD62L after TNFi treatment. OC number was reduced in patients at baseline when compared to controls. OC specific gene expression was reduced in circulating OC precursors after TNFi treatment. However, when cultured in OC differentiating conditions, OC precursors from AS TNFi-treated patients showed increased activity as compared to baseline.In AS patients, TNFi treatment reduces systemic pro osteoclastogenic stimuli. However, OC precursors from AS patients exposed to TNFi therapy have increased in vitro activity in response to osteoclastogenic stimuli.

  15. THE EXTERNAL FACTORS OF STUDENTS’ INVOLVEMENT IN SPEAKING ACTIVITY AT SMP PROGRESIF BUMI SHALAWAT

    Directory of Open Access Journals (Sweden)

    M.A. Nurul Haikal

    2016-07-01

    Full Text Available This research is conducted to know what factors that influence the students’ involvement in speaking activity in order to practice their speaking skill and what strategies that the teacher used to encourage those external factors. This research uses descriptive qualitative method. There are two instruments used for this research, namely, class observation and interview. Based on the results of class observation and interview, the researcher concludes that teacher factor gives the greatest impact on students’ involvement and the appropriate strategies can support those external factors.

  16. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation.

    LENUS (Irish Health Repository)

    Ni Ainle, Fionnuala

    2009-08-20

    Protamine sulfate is a positively charged polypeptide widely used to reverse heparin-induced anticoagulation. Paradoxically, prospective randomized trials have shown that protamine administration for heparin neutralization is associated with increased bleeding, particularly after cardiothoracic surgery with cardiopulmonary bypass. The molecular mechanism(s) through which protamine mediates this anticoagulant effect has not been defined. In vivo administration of pharmacologic doses of protamine to BALB\\/c mice significantly reduced plasma thrombin generation and prolonged tail-bleeding time (from 120 to 199 seconds). Similarly, in pooled normal human plasma, protamine caused significant dose-dependent prolongations of both prothrombin time and activated partial thromboplastin time. Protamine also markedly attenuated tissue factor-initiated thrombin generation in human plasma, causing a significant decrease in endogenous thrombin potential (41% +\\/- 7%). As expected, low-dose protamine effectively reversed the anticoagulant activity of unfractionated heparin in plasma. However, elevated protamine concentrations were associated with progressive dose-dependent reduction in thrombin generation. To assess the mechanism by which protamine mediates down-regulation of thrombin generation, the effect of protamine on factor V activation was assessed. Protamine was found to significantly reduce the rate of factor V activation by both thrombin and factor Xa. Protamine mediates its anticoagulant activity in plasma by down-regulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation.

  17. [Dependence of EGF receptor and STAT factor activation on redox of A431 cells].

    Science.gov (United States)

    Gonchar, I V; Burova, E B; Dorosh, V N; Gamaleĭ, I A; Nikol'skiĭ, N N

    2003-01-01

    Reactive oxygen species (ROS) were established to play an important role in cellular signaling as second messengers by integrating different pathways. Recently, we showed that EGF initiated a rapid tyrosine phosphorylation of both EGF-receptor and STAT factors with simultaneous increase in the intracellular ROS level. Now, we have investigated the effect of intracellular red-ox state on EGF- and H2O2-induced activation of EGF receptor, STAT1 and STAT3. We demonstrated that the pretreatment of A431 cells with antioxidant N-acetyl-L-cysteine (NAC) partly reduced the level of EGF-induced phosphorylation of proteins under investigation. Besides, H2O2-induced activation of EGF receptor, and STAT factors was fully prevented by NAC pretreatment. The inhibition of ROS generation by DPI declined EGF-dependent activation of EGF receptor and STAT factors to basal level. Our results demonstrate the essential role of cellular red-ox status in the modulation of EGF-mediated activation of receptor and STAT factors. We have postulated that EGF-induced ROS generation is a very important initial event promoting physiological activation of EGF receptor and subsequent STAT factor activation.

  18. The translation initiation factor 3f (eIF3f exhibits a deubiquitinase activity regulating Notch activation.

    Directory of Open Access Journals (Sweden)

    Julien Moretti

    Full Text Available Activation of the mammalian Notch receptor after ligand binding relies on a succession of events including metalloprotease-cleavage, endocytosis, monoubiquitination, and eventually processing by the gamma-secretase, giving rise to a soluble, transcriptionally active molecule. The Notch1 receptor was proposed to be monoubiquitinated before its gamma-secretase cleavage; the targeted lysine has been localized to its submembrane domain. Investigating how this step might be regulated by a deubiquitinase (DUB activity will provide new insight for understanding Notch receptor activation and downstream signaling. An immunofluorescence-based screening of an shRNA library allowed us to identify eIF3f, previously known as one of the subunits of the translation initiation factor eIF3, as a DUB targeting the activated Notch receptor. We show that eIF3f has an intrinsic DUB activity. Knocking down eIF3f leads to an accumulation of monoubiquitinated forms of activated Notch, an effect counteracted by murine WT eIF3f but not by a catalytically inactive mutant. We also show that eIF3f is recruited to activated Notch on endocytic vesicles by the putative E3 ubiquitin ligase Deltex1, which serves as a bridging factor. Finally, catalytically inactive forms of eIF3f as well as shRNAs targeting eIF3f repress Notch activation in a coculture assay, showing that eIF3f is a new positive regulator of the Notch pathway. Our results support two new and provocative conclusions: (1 The activated form of Notch needs to be deubiquitinated before being processed by the gamma-secretase activity and entering the nucleus, where it fulfills its transcriptional function. (2 The enzyme accounting for this deubiquitinase activity is eIF3f, known so far as a translation initiation factor. These data improve our knowledge of Notch signaling but also open new avenues of research on the Zomes family and the translation initiation factors.

  19. A New Microsphere-Based Immunoassay for Measuring the Activity of Transcription Factors

    Directory of Open Access Journals (Sweden)

    Tsai Chueh-Jen

    2010-01-01

    Full Text Available Abstract There are several traditional and well-developed methods for analyzing the activity of transcription factors, such as EMSA, enzyme-linked immunosorbent assay, and reporter gene activity assays. All of these methods have their own distinct disadvantages, but none can analyze the changes in transcription factors in the few cells that are cultured in the wells of 96-well titer plates. Thus, a new microsphere-based immunoassay to measure the activity of transcription factors (MIA-TF was developed. In MIA-TF, NeutrAvidin-labeled microspheres were used as the solid phase to capture biotin-labeled double-strand DNA fragments which contain certain transcription factor binding elements. The activity of transcription factors was detected by immunoassay using a transcription factor-specific antibody to monitor the binding with the DNA probe. Next, analysis was performed by flow cytometry. The targets hypoxia-inducible factor-1α (HIF-1α and nuclear factor-kappa B (NF-κB were applied and detected in this MIA-TF method; the results that we obtained demonstrated that this method could be used to monitor the changes of NF-κB or HIF within 50 or 100 ng of nuclear extract. Furthermore, MIA-TF could detect the changes in NF-κB or HIF in cells that were cultured in wells of a 96-well plate without purification of the nuclear protein, an important consideration for applying this method to high-throughput assays in the future. The development of MIA-TF would support further progress in clinical analysis and drug screening systems. Overall, MIA-TF is a method with high potential to detect the activity of transcription factors.

  20. Factor Xa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation

    NARCIS (Netherlands)

    Borensztajn, Keren; Stiekema, Jurrieen; Nijmeijer, Sebastiaan; Reitsmalf, Pieter H.; Peppelenbosch, Maikel P.; Spek, C. Arnold

    Coagulation proteases have been suggested to play a role in the pathogenesis of tissue remodeling and fibrosis. We therefore assessed the proinflammatory and fibroproliferative effects of coagulation protease factor (F)Xa. We show that FXa elicits a signaling response in C2C12 and NIH3T3

  1. Plant NAC-type transcription factor proteins contain a NARD domain for repression of transcriptional activation.

    Science.gov (United States)

    Hao, Yu-Jun; Song, Qing-Xin; Chen, Hao-Wei; Zou, Hong-Feng; Wei, Wei; Kang, Xu-Sheng; Ma, Biao; Zhang, Wan-Ke; Zhang, Jin-Song; Chen, Shou-Yi

    2010-10-01

    Plant-specific transcription factor NAC proteins play essential roles in many biological processes such as development, senescence, morphogenesis, and stress signal transduction pathways. In the NAC family, some members function as transcription activators while others act as repressors. In the present study we found that though the full-length GmNAC20 from soybean did not have transcriptional activation activity, the carboxy-terminal activation domain of GmNAC20 had high transcriptional activation activity in the yeast assay system. Deletion experiments revealed an active repression domain with 35 amino acids, named NARD (NAC Repression Domain), in the d subdomain of NAC DNA-binding domain. NARD can reduce the transcriptional activation ability of diverse transcription factors when fused to either the amino-terminal or the carboxy-terminal of the transcription factors. NARD-like sequences are also present in other NAC family members and they are functional repression domain when fused to VP16 in plant protoplast assay system. Mutation analysis of conserved amino acid residues in NARD showed that the hydrophobic LVFY motif may partially contribute to the repression function. It is hypothesized that the interactions between the repression domain NARD and the carboxy-terminal activation domain may finally determine the ability of NAC family proteins to regulate downstream gene expressions.

  2. The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia

    Science.gov (United States)

    Zhang, Qian; Doucet, Michele; Tomlinson, Ryan E; Han, Xiaobin; Quarles, L Darryl; Collins, Michael T; Clemens, Thomas L

    2016-01-01

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 (FGF23) by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-1α (HIF-1α) in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-1α mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-1α and FGF23 were co-localized in spindle-shaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-1α protein. Transfection of MC3T3-E1 and Saos-2 cells with a HIF-1α expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-1α inhibitors decreased HIF-1α and FGF23 protein accumulation and inhibited HIF-1α-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-1α consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-1α inhibitor. These results show for the first time that HIF-1α is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-1α activity in TIO contributes to the aberrant FGF23 production in these patients. PMID:27468359

  3. A new automated method for continuous registration of factor VII activation in vitro. Activation is accelerated by the concentration of factor VII and the activity state of the protein

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, J; Gram, J

    1994-01-01

    When a plasma sample is exposed to tissue factor, single-chain factor VII (FVII) is gradually converted to the active two-chain form (FVIIa). In the present study, we have constructed a measurement system, which allows continuous registration of the activation of FVII to FVIIa in vitro....... In this system, FVII activation follows parabolic kinetic after an initial lag-phase. The slope of the linear phase is a measure of the protein concentration of factor VII (FVIItotal), while the length of the non-linear phase represents the velocity of FVII activation. The time required for complete activation...... of FVII is inversely related to both FVIItotal and the relative amount of FVIIa in the sample. In future studies, this new measurement system will make it possible to study the process of FVII activation in different samples, and to examine how varying concentrations of exogenous added components affect...

  4. Gastrointestinal growth factors and hormones have divergent effects on Akt activation

    Science.gov (United States)

    Berna, Marc J.; Tapia, Jose A.; Sancho, Veronica; Thill, Michelle; Pace, Andrea; Hoffmann, K. Martin; Gonzalez-Fernandez, Lauro; Jensen, Robert T.

    2009-01-01

    Akt is a central regulator of apoptosis, cell growth and survival. Growth factors and some G-protein-coupled receptors (GPCR) regulate Akt. Whereas growth-factor activation of Akt has been extensively studied, the regulation of Akt by GPCR's, especially gastrointestinal hormones/neurotransmitters, remains unclear. To address this area, in this study the effects of GI growth factors and hormones/neurotransmitters were investigate in rat pancreatic acinar cells which are high responsive to these agents. Pancreatic acini expressed Akt and 5 of 7 known pancreatic growth-factors stimulate Akt phosphorylation (T308, S473) and translocation. These effects are mediated by p85 phosphorylation and activation of PI3K. GI hormones increasing intracellular cAMP had similar effects. However, GI-hormones/neurotransmitters[CCK, bombesin,carbachol] activating phospholipase C (PLC) inhibited basal and growth-factor-stimulated Akt activation. Detailed studies with CCK, which has both physiological and pathophysiological effects on pancreatic acinar cells at different concentrations, demonstrated CCK has a biphasic effect: at low concentrations(pM) stimulating Akt by a Src-dependent mechanism and at higher concentrations(nM) inhibited basal and stimulated Akt translocation, phosphorylation and activation, by de-phosphorylating p85 resulting in decreasing PI3K activity. This effect required activation of both limbs of the PLC-pathway and a protein tyrosine phosphatase, but was not mediated by p44/42 MAPK, Src or activation of a serine phosphatase. Akt inhibition by CCK was also found in vivo and in Panc-1 cancer cells where it inhibited serum-mediated rescue from apoptosis. These results demonstrate that GI growth factors as well as gastrointestinal hormones/neurotransmitters with different cellular basis of action can all regulate Akt phosphorylation in pancreatic acinar cells. This regulation is complex with phospholipase C agents such as CCK, because both stimulatory and inhibitory

  5. The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7).

    OpenAIRE

    Bagheri-Yarmand, R.; Kourbali, Y; Mabilat, C; Morère, J. F.; Martin, A; Lu, H; Soria, C; Jozefonvicz, J; Crépin, M

    1998-01-01

    Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) blocks basic fibroblast growth factor (FGF-2)-dependent cell proliferation of a human breast epithelial line (HBL100), suggesting its potential role as a potent antiangiogenic substance. The derived cell line (HH9), which was transformed with the hst/FGF4 gene, has been shown to be highly proliferative in vitro and to induce angiogenic tumours in nude mice. We show here that CMDB7 inhibits the mitogenic activities of t...

  6. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Jinah Han

    2015-02-01

    Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

  7. Identifying factors hampering physical activity in longstanding rheumatoid arthritis: what is the role of glucocorticoid therapy?

    Science.gov (United States)

    van der Goes, M C; Hoes, J N; Cramer, M J; van der Veen, M J; van der Werf, J H; Bijlsma, J W J; Jacobs, J W G

    2014-01-01

    To identify factors hampering the level of physical activity in longstanding rheumatoid arthritis (RA) patients, and to evaluate the effects of glucocorticoid therapy on physical activity. Patient characteristics, disease characteristics and cardiovascular parameters were recorded in 170 patients, who participated in a study about glucose metabolism in longstanding RA treated with or without glucocorticoids. Disease activity scores (DAS28) were calculated and x-rays of hands and feet were taken and scored according to the Sharp van der Heijde score (SHS). Participants completed the health assessment questionnaire and short questionnaire to assess health-enhancing physical activity (SQUASH), which reflect physical disability and physical activity, respectively. Adherence rates to recommendations on physical activity were calculated, and patients were categorised as fully adhering, insufficiently adhering (adherence on less than the recommended number of days per week) or inactive (adherence on none of the days). Forty-four percent of the patients showed adherence to the recommended minimum level of physical activity, and 22% were classified as inactive. Higher DAS28 and SHS, glucocorticoid therapy, and presence of cardiovascular risk factors were associated with lower total SQUASH physical activity scores univariately. In a multivariate model, higher age, higher body mass index (BMI), higher DAS28, and higher SHS negatively influenced the score significantly; cardiovascular risk factors and glucocorticoid therapy were no longer significantly influencing physical activity. Physical activity in longstanding RA is hampered by higher age, higher BMI, higher disease activity, and more radiographic joint damage. Glucocorticoid therapy was not identified as independent risk factor in multivariate analyses.

  8. Using avian radar to examine relationships among avian activity, bird strikes, and meteorological factors

    Science.gov (United States)

    Coates, Peter S.; Casazza, Michael L.; Halstead, Brian J.; Fleskes, Joseph P.; Laughlin, James A.

    2011-01-01

    Radar systems designed to detect avian activity at airfields are useful in understanding factors that influence the risk of bird and aircraft collisions (bird strikes). We used an avian radar system to measure avian activity at Beale Air Force Base, California, USA, during 2008 and 2009. We conducted a 2-part analysis to examine relationships among avian activity, bird strikes, and meteorological and time-dependent factors. We found that avian activity around the airfield was greater at times when bird strikes occurred than on average using a permutation resampling technique. Second, we developed generalized linear mixed models of an avian activity index (AAI). Variation in AAI was first explained by seasons that were based on average migration dates of birds at the study area. We then modeled AAI by those seasons to further explain variation by meteorological factors and daily light levels within a 24-hour period. In general, avian activity increased with decreased temperature, wind, visibility, precipitation, and increased humidity and cloud cover. These effects differed by season. For example, during the spring bird migration period, most avian activity occurred before sunrise at twilight hours on clear days with low winds, whereas during fall migration, substantial activity occurred after sunrise, and birds generally were more active at lower temperatures. We report parameter estimates (i.e., constants and coefficients) averaged across models and a relatively simple calculation for safety officers and wildlife managers to predict AAI and the relative risk of bird strike based on time, date, and meteorological values. We validated model predictability and assessed model fit. These analyses will be useful for general inference of avian activity and risk assessment efforts. Further investigation and ongoing data collection will refine these inference models and improve our understanding of factors that influence avian activity, which is necessary to inform

  9. Nuclear factor-κB p65 (RelA) transcription factor is constitutively activated in human colorectal carcinoma tissue

    Institute of Scientific and Technical Information of China (English)

    Liang-Liang Yu; Hong-Gang Yu; Jie-Ping Yu; He-Sheng Luo; Xi-Ming Xu; Jun-Hua Li

    2004-01-01

    AIM: Activation of transcription factor nuclear factor-κB (NF-κB) has been shown to play a role in cell proliferation,apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-κB was constitutively activated in human colorectal tumor tissues and, if so, to determine the role of NF-κB in colorectal tumorigenesis, and furthermore, to determine the association of RelA expression with tumor cell apoptosis and the expression of Bcl-2 and Bcl-xL.METHODS: Paraffin sections of normal epithelial, adenomatous and adenocarcinoma tissues were analysed immunohistochemically for expression of RelA, Bcl-2 and Bcl-xL proteins.Electrophoretic mobility shift assay (EMSA) was used to confirm the increased nuclear translocation of RelA in colorectal tumor tissues. The mRNA expressions of Bcl-2 and Bcl-xL were determined by reverse transcription polymerase chain reaction (RT-PCR) analysis. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method.RESULTS: The activity of NF-κB was significantly higher in adenocarcinoma tissue in comparison with that in adenomatous and normal epithelial tissues. The apoptotic index (AI)significantly decreased in the transition from adenoma to adenocarcinoma. Meanwhile, the expressions of Bcl-2 and Bcl-xL protein and their mRNAs were significantly higher in adenocarcinoma tissues than that in adenomatous and normal epithelial tissues.CONCLUSION: NF-κB may inhibit apoptosis via enhancing the expression of the apoptosis genes Bcl-2 and BCl-xL. And the increased expression of RelA/nuclear factor-κB plays an important rote in the pathogenesis of colorectal carcinoma.

  10. Inactivation of staphylococcal virulence factors using a light-activated antimicrobial agent

    Directory of Open Access Journals (Sweden)

    Wilson Michael

    2009-10-01

    Full Text Available Abstract Background One of the limitations of antibiotic therapy is that even after successful killing of the infecting microorganism, virulence factors may still be present and cause significant damage to the host. Light-activated antimicrobials show potential for the treatment of topical infections; therefore if these agents can also inactivate microbial virulence factors, this would represent an advantage over conventional antibiotic therapy. Staphylococcus aureus produces a wide range of virulence factors that contribute to its success as a pathogen by facilitating colonisation and destruction of host tissues. Results In this study, the ability of the light-activated antimicrobial agent methylene blue in combination with laser light of 665 nm to inactivate staphylococcal virulence factors was assessed. A number of proteinaceous virulence factors were exposed to laser light in the presence of methylene blue and their biological activities re-determined. The activities of V8 protease, α-haemolysin and sphingomyelinase were shown to be inhibited in a dose-dependent manner by exposure to laser light in the presence of methylene blue. Conclusion These results suggest that photodynamic therapy could reduce the harmful impact of preformed virulence factors on the host.

  11. Female reproductive factors are associated with objectively measured physical activity in middle-aged women

    Science.gov (United States)

    Kulmala, Janne; Aukee, Pauliina; Hakonen, Harto; Kujala, Urho M.; Lowe, Dawn A.; Kovanen, Vuokko; Tammelin, Tuija; Sipilä, Sarianna

    2017-01-01

    Physical activity improves health and may delay the onset of several chronic diseases. For women in particular, the rate of these diseases accelerates at middle age; therefore it is important to identify the determinants of health-enhancing physical activity during midlife in this population. In this study, we focused on determinants that are unique to the female sex, such as childbearing and menopause. The main objective was to characterize the level of physical activity and differences between active and inactive middle-aged Finnish women. In addition, we examined the association of physical activity with female reproductive factors at midlife. The study population consisted of 647 women aged 48 to 55 years who participated in our Estrogenic Regulation of Muscle Apoptosis (ERMA) study during the period from 2015 to 2016. Physical activity was measured objectively using hip-worn accelerometers for seven consecutive days. The outcome measures included the amounts of light intensity physical activity and moderate to vigorous intensity physical activity accumulated in bouts of at least 10 minutes (MVPA10). MVPA10 was used to determine whether women were placed in the active (≥150 min/week) or inactive (pelvic floor dysfunction as independent variables. We found that a large portion (61%) of Finnish middle-aged women did not meet the physical activity recommendations of 150 minutes of MVPA10 per week. In the studied cohort, 78% of women experienced menopausal symptoms, and 54% exhibited pelvic floor dysfunction. Perceived menopausal symptoms were associated with greater light physical activity. Perceived pelvic floor dysfunction was associated with lower MVPA10. According to the fully adjusted multiple linear regression models, reproductive factors explained 6.0% of the variation of MVPA10 and 7.5% of the variation of light physical activity. The results increase our knowledge of the factors related to physical activity participation among middle-aged women and

  12. Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation

    DEFF Research Database (Denmark)

    Hauge, Camilla; Antal, Torben L; Hirschberg, Daniel

    2007-01-01

    investigated the role of the third, so-called turn motif phosphate, also located in the tail, in the AGC kinases PKB, S6K, RSK, MSK, PRK and PKC. We report cooperative action of the HM phosphate and the turn motif phosphate, because it binds a phosphoSer/Thr-binding site above the glycine-rich loop within...... the kinase domain, promoting zipper-like association of the tail with the kinase domain, serving to stabilize the HM in its kinase-activating binding site. We present a molecular model for allosteric activation of AGC kinases by the turn motif phosphate via HM-mediated stabilization of the alphaC helix. In S......6K and MSK, the turn motif phosphate thereby also protects the HM from dephosphorylation. Our results suggest that the mechanism described is a key feature in activation of upto 26 human AGC kinases....

  13. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

    Directory of Open Access Journals (Sweden)

    Simon Hauerslev

    Full Text Available Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  14. Anti-inflammatory activity on mice of extract of Ganoderma lucidum grown on rice via modulation of MAPK and NF-κB pathways.

    Science.gov (United States)

    Hasnat, Md Abul; Pervin, Mehnaz; Cha, Kyu Min; Kim, Si Kwan; Lim, Beong Ou

    2015-06-01

    Ganoderma lucidum is a popular medicinal mushroom with anti-inflammatory potential. In the present study, the aim was to determine the anti-inflammatory effect and mode of action of G. lucidum grown on germinated brown rice (GLBR) in a mouse model of colitis. It was shown that GLBR suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated macrophages and decreased the expression of COX-2, TNF-α, iNOS, IL-1β, IL-6, and IL-10 mRNAs. GLBR also inhibited activation of p38, ERK, JNK, MAPKs, and nuclear factor kappa-B (NF-κB). In a mouse model of colitis, colonic mucosal injury was evaluated using macroscopic, biochemical, and histopathological testing. Disease activity index (DAI), macroscopic score, and histological score significantly decreased upon GLBR treatment. Moreover, immunofluorescence studies indicated that DSS activates nuclear translocation of NF-κB in colon tissue, which is attenuated by GLBR extract. These findings suggest that GLBR is protective against colitis via inhibition of MAPK phosphorylation and NF-κB activation.

  15. Sociocultural factors relating to Tongans' and Indigenous Fijians' patterns of eating, physical activity and body size.

    Science.gov (United States)

    Mavoa, Helen M; McCabe, Marita

    2008-01-01

    This paper reviews literature between 1974 and 2007 that addresses the impact of sociocultural factors on reported patterns of eating, physical activity (activity) and body size of Tongans and indigenous Fijians (Fijians) in their countries of origin. There have been changes in diet (more imported and fewer traditional foods), activity (reduced, especially in urban settings), residence (rural-urban shift) and body size (increased obesity and at a younger age). The prevalence of overweight/obesity in Tongans and Fijians has increased rapidly over the last two decades and remains among the highest in the world (>80% in Tonga; >40% in Fiji), with more females reported to be obese than males. The few studies that investigated sociocultural influences on patterns of eating, activity and/or body size in this population have examined the impact of hierarchical organisation, rank and status (sex, seniority), values (respect, care, co-operation) and/or role expectations. It is important to examine how sociocultural factors influence eating, activity and body size in order to i) establish factors that promote or protect against obesity, ii) inform culturally-appropriate interventions to promote healthy lifestyles and body size, and iii) halt the obesity epidemic, especially in cultural groups with a high prevalence of obesity. There is an urgent need for more systematic investigations of key sociocultural factors, whilst taking into account the complex interplay between sociocultural factors, behaviours and other influences (historical; socioeconomic; policy; external global influences; physical environment).

  16. Foot-and-mouth disease virus leader proteinase inhibits dsRNA-induced type I interferon transcription by decreasing interferon regulatory factor 3/7 in protein levels

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Dang; Fang, Liurong; Luo, Rui; Ye, Rui; Fang, Ying; Xie, Lilan; Chen, Huanchun [Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); Xiao, Shaobo, E-mail: shaoboxiao@yahoo.com [Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China)

    2010-08-13

    Research highlights: {yields} FMDV L{sup pro} inhibits poly(I:C)-induced IFN-{alpha}1/{beta} mRNA expression. {yields} L{sup pro} inhibits MDA5-mediated activation of the IFN-{alpha}1/{beta} promoter. {yields} L{sup pro} significantly reduced the transcription of multiple IRF-responsive genes. {yields} L{sup pro} inhibits IFN-{alpha}1/{beta} promoter activation by decreasing IRF-3/7 in protein levels. {yields} The ability to process eIF-4G of L{sup pro} is not necessary to inhibit IFN-{alpha}1/{beta} activation. -- Abstract: The leader proteinase (L{sup pro}) of foot-and-mouth disease virus (FMDV) has been identified as an interferon-{beta} (IFN-{beta}) antagonist that disrupts the integrity of transcription factor nuclear factor {kappa}B (NF-{kappa}B). In this study, we showed that the reduction of double stranded RNA (dsRNA)-induced IFN-{alpha}1/{beta} expression caused by L{sup pro} was also associated with a decrease of interferon regulatory factor 3/7 (IRF-3/7) in protein levels, two critical transcription factors for activation of IFN-{alpha}/{beta}. Furthermore, overexpression of L{sup pro} significantly reduced the transcription of multiple IRF-responsive genes including 2',5'-OAS, ISG54, IP-10, and RANTES. Screening L{sup pro} mutants indicated that the ability to process eIF-4G of L{sup pro} is not required for suppressing dsRNA-induced activation of the IFN-{alpha}1/{beta} promoter and decreasing IRF-3/7 expression. Taken together, our results demonstrate that, in addition to disrupting NF-{kappa}B, L{sup pro} also decreases IRF-3/7 expression to suppress dsRNA-induced type I IFN production, suggesting multiple strategies used by FMDV to counteract the immune response to viral infection.

  17. Roscovitine in combination with calcium ionophore induces oocyte activation through reduction of M-phase promoting factor activity in mice.

    Science.gov (United States)

    Iba, Tomomi; Yano, Yuya; Umeno, Mayumi; Hinokio, Kenji; Kuwahara, Akira; Irahara, Minoru; Yamano, Shuji; Yasui, Toshiyuki

    2012-11-01

    The aim of the present study was to determine oocyte activation and change in M-phase promoting factor (MPF) activity induced by treatment with calcium ionophore and roscovitine in comparison with those induced by treatment with roscovitine alone and treatment with calcium ionophore and puromycin in mice. Freshly ovulated oocytes obtained from 6-8-week-old mice were divided into five groups (no activation treatment; 5 μM calcium ionophore A23187; 50 μM roscovitine; 5 μM calcium ionophore and 10 μg/ml puromycin; and 5 μM calcium ionophore and 50 μM roscovitine) and were incubated for 6 h. Oocyte activation, assessed by morphological changes, and changes in MPF activity in the five groups at 0, 2, 4 and 6 h of incubation were examined. Activated oocytes were defined as oocytes with at least one pronucleus. Oocytes treated with roscovitine alone were not activated during the 6-h incubation period. All of the oocytes in the calcium ionophore with puromycin group and in the calcium ionophore with roscovitine group were activated. The percentage activity of MPF in oocytes treated with roscovitine alone was decreased after 2 h and increased after 4 h of incubation. The percentage activity of MPF in oocytes treated with calcium ionophore and roscovitine was significantly decreased with suppression of MPF activity being maintained for 6 h, and this change was similar to that in oocytes treated with calcium ionophore and puromycin. Roscovitine with calcium ionophore is effective for induction of oocyte activation through suppression of MPF activity in mice.

  18. Nuclear Factor-kappaB controls the reaggregation of 3D neurosphere cultures in vitro

    Directory of Open Access Journals (Sweden)

    D Widera

    2006-05-01

    Full Text Available The approach of reaggregation involves the regeneration and self-renewal of histotypical 3D spheres from isolated tissue kept in suspension culture. Reaggregated spheres can be used as tumour, genetic, biohybrid and neurosphere models. In addition the functional superiority of 3D aggregates over conventional 2D cultures developed the use of neurospheres for brain engineering of CNS diseases. Thus 3D aggregate cultures created enormous interest in mechanisms that regulate the formation of multicellular aggregates in vitro. Here we analyzed mechanisms guiding the development of 3D neurosphere cultures. Adult neural stem cells can be cultured as self-adherent clusters, called neurospheres. Neurospheres are characterised as heterogeneous clusters containing unequal stem cell sub-types. Tumour necrosis factor-alpha (TNF- alpha is one of the crucial inflammatory cytokines with multiple actions on several cell types. TNF- alpha strongly activates the canonical Nuclear Factor Kappa-B (NF-kappaB pathway. In order to investigate further functions of TNF in neural stem cells (NSCs we tested the hypothesis that TNF is able to modulate the motility and/or migratory behaviour of SVZ derived adult neural stem cells. We observed a significantly faster sphere formation in TNF treated cultures than in untreated controls. The very fast aggregation of isolated NSCs (<2h is a commonly observed phenomenon, though the mechanisms of 3D neurosphere formation remain largely unclear. Here we demonstrate for the first time, increased aggregation and enhanced motility of isolated NSCs in response to the TNF-stimulus. Moreover, this phenomenon is largely dependent on activated transcription factor NF-kappaB. Both, the pharmacological blockade of NF-kappaB pathway by pyrrolidine dithiocarbamate (PDTC or Bay11-7082 and genetic blockade by expression of a transdominant-negative super-repressor IkappaB-AA1 led to decreased aggregation.

  19. Sp3 controls fibroblast growth factor receptor 4 gene activity during myogenic differentiation.

    Science.gov (United States)

    Cavanaugh, Eric; DiMario, Joseph X

    2017-03-27

    Fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling is a critical component in the regulation of myoblast proliferation and differentiation. The transient FGFR4 gene expression during the transition from proliferating myoblasts to differentiated myotubes indicates that FGFR4 regulates this critical phase of myogenesis. The Specificity Protein (SP) family of transcription factors controls FGFR family member gene activity. We sought to determine if members of the Sp family regulate mouse FGFR4 gene activity during myogenic differentiation. RT-PCR and western blot analysis of FGFR4 mRNA and protein revealed transient expression over 72h, with peak expression between 24 and 36h after addition of differentiation medium to C2C12 myogenic cultures. Sp3 also displayed a transient expression pattern with peak expression occurring after 6h of differentiation. We cloned a 1527bp fragment of the mouse FGFR4 promoter into a luciferase reporter. This FGFR4 promoter contains eight putative Sp binding sites and directed luciferase gene activity comparable to native FGFR4 expression. Overexpression of Sp1 and Sp3 showed that Sp1 repressed FGFR4 gene activity, and Sp3 activated FGFR4 gene activity during myogenic differentiation. Mutational analyses of multiple Sp binding sites within the FGFR4 promoter revealed that three of these sites were transcriptionally active. Electromobility shift assays and chromatin immunoprecipitation of the area containing the activator sites showed that Sp3 bound to this promoter location.

  20. Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

    LENUS (Irish Health Repository)

    Gleeson, Eimear M

    2013-07-19

    Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor

  1. Factors Related to Meeting Physical Activity Guidelines in Active College Students: A Social Cognitive Perspective

    Science.gov (United States)

    Farren, G. L.; Zhang, T.; Martin, S. B.; Thomas, K. T.

    2017-01-01

    Objective: To examine the relations of sex, exercise self-efficacy, outcome expectations, and social support with meeting physical activity guidelines (PAGs). Participants: Three hundred ninety-six college students participated in this study in the summer 2013. Methods: Students completed online questionnaires that assessed physical activity…

  2. Factors Related to Meeting Physical Activity Guidelines in Active College Students: A Social Cognitive Perspective

    Science.gov (United States)

    Farren, G. L.; Zhang, T.; Martin, S. B.; Thomas, K. T.

    2017-01-01

    Objective: To examine the relations of sex, exercise self-efficacy, outcome expectations, and social support with meeting physical activity guidelines (PAGs). Participants: Three hundred ninety-six college students participated in this study in the summer 2013. Methods: Students completed online questionnaires that assessed physical activity…

  3. Factors Associated with Physical Activity among Macedonian Adolescents in Albanian Ethnic Community

    Science.gov (United States)

    GONTAREV, Seryozha; KALAC, Ruzdija; AMETI, Vullnet; REDJEPI, Agim

    2016-01-01

    Background: The purpose of this study was to determine the relationship of demographic, psychological, social and environmental factors with physical activity and to determine whether indicators of physical activity differ by gender among Macedonian adolescents from Albanian ethnic community from 11 to 14 yr (N = 886). Methods: Research were conducted in 2014 in several primary schools randomly selected from Tetovo and Gostivar region of the R. Macedonia. Students completed a questionnaire which examined their level of participation in physical activity and sedentary behavior along with a number of potential correlates. Hierarchical regression was used to explore the relationship between hypothesised factors and physical activity. Results: The boys unlike the girls showed significantly higher levels of physical activity (P=0.001). Respondents of both genders who perceive greater benefits from the physical activity (P=0.010). They have more confidence in their abilities (P=0.001), enjoy more in the physical activities (P=0.016), perceive greater social support from friends (P=0.008) and parents (P=0.001) and have higher levels of physical activity. Conclusions: The results indicate the importance of developing a national plan and program to promote physical activity in order to help young people to change unhealthy lifestyle habits and increase the physical activity, thus improving their health. PMID:27252917

  4. Energy Optimization And Calculation Of Dose Absorption Enhancement Factor In Photon Activation Therapy

    Directory of Open Access Journals (Sweden)

    Hassan Ranjbar

    2010-06-01

    Full Text Available Introduction: Secondary radiation such as photoelectrons, Auger electrons and characteristic radiations cause a local boost in dose for a tumor when irradiated with an external X-ray beam after being loaded with elements capable of activating the tumor, e.g.; I and Gd. Materials and Methods:  In this investigation, the MCNPX code was used for simulation and calculation of dose enhancement factor for a tumor loaded with activating elements. The designed model comprised the X-ray source, phantom (target tissue and loaded tumor with activating agent, detector, interactions modeling and results. The source was defined as monochromatic and plane surface situated at 50 cm (z = 50. Phantom geometry was a 10 × 10 × 10 cm3 cube centered at (0, 0, 0 with a 2.2 × 2.2 × 2.2 cm3 cubic tumor with a center located at 3 cm depth inside the phantom Results: Dose enhancement factor and optimum energy in radiotherapy are evaluated using the photon activation therapy method. Result show that the dose enhancement factor increases with activating concentration in the tumor. The maximum dose enhancement factor for iodine in the tumor occurs for photons in the energy range of 50-60 keV. Dose uniformity is less for lower energy photons within the activated region inside the tumor. Results indicate that the dose enhancement factor varies linearly with the activating concentration agent. Discussion and Conclusion: In this study, the obtained results point out a considerable enhancement in dose in the presence of activating agents in the tumor regions.

  5. Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors.

    Science.gov (United States)

    Liu, Hesheng; Stufflebeam, Steven M; Sepulcre, Jorge; Hedden, Trey; Buckner, Randy L

    2009-12-01

    Cerebral lateralization is a fundamental property of the human brain and a marker of successful development. Here we provide evidence that multiple mechanisms control asymmetry for distinct brain systems. Using intrinsic activity to measure asymmetry in 300 adults, we mapped the most strongly lateralized brain regions. Both men and women showed strong asymmetries with a significant, but small, group difference. Factor analysis on the asymmetric regions revealed 4 separate factors that each accounted for significant variation across subjects. The factors were associated with brain systems involved in vision, internal thought (the default network), attention, and language. An independent sample of right- and left-handed individuals showed that hand dominance affects brain asymmetry but differentially across the 4 factors supporting their independence. These findings show the feasibility of measuring brain asymmetry using intrinsic activity fluctuations and suggest that multiple genetic or environmental mechanisms control cerebral lateralization.

  6. Factors influencing the activity and thermostability of immobilized porcine pancreatic lipase.

    Science.gov (United States)

    Kéry, V; Haplová, J; Tihlárik, K; Schmidt, S

    1990-01-01

    Lipase from porcine pancreas was immobilized on cellulose beads having various degrees of hydrophobicity, by covalent linking and by hydrophobic adsorption. Lipolytic activity was measured in heterogeneous organic-aqueous systems of various hydrophobicities using olive oil as a substrate. The main factors influencing lipase activity were hydrophobicity of the reaction mixture and of the carrier. Carriers with increased hydrophobicity enhanced lipase activity more than less hydrophobic ones. Lipase immobilized covalently on cellulose beads was less active than that adsorbed onto tritylcellulose but was considerably more thermostable.

  7. Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice.

    Science.gov (United States)

    Li, Weidong; Hua, Baojin; Saud, Shakir M; Lin, Hongsheng; Hou, Wei; Matter, Matthias S; Jia, Libin; Colburn, Nancy H; Young, Matthew R

    2015-10-01

    Colorectal cancer, a leading cause of cancer death, has been linked to inflammation and obesity. Berberine, an isoquinoline alkaloid, possesses anti-inflammatory, anti-diabetes and anti-tumor properties. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, berberine treated mice showed a 60% reduction in tumor number (P = 0.009), a 48% reduction in tumors 4 mm (P = 0.02) compared to vehicle treated mice. Berberine also decreased AOM/DSS induced Ki-67 and COX-2 expression. In vitro analysis showed that in addition to its anti-proliferation activity, berberine also induced apoptosis in colorectal cancer cell lines. Berberine activated AMP-activated protein kinase (AMPK), a major regulator of metabolic pathways, and inhibited mammalian target of rapamycin (mTOR), a downstream target of AMPK. Furthermore, 4E-binding protein-1 and p70 ribosomal S6 kinases, downstream targets of mTOR, were down regulated by berberine treatment. Berberine did not affect Liver kinase B1 (LKB1) activity or the mitogen-activated protein kinase pathway. Berberine inhibited Nuclear Factor kappa-B (NF-κB) activity, reduced the expression of cyclin D1 and survivin, induced phosphorylation of p53 and increased caspase-3 cleavage in vitro. Berberine inhibition of mTOR activity and p53 phosphorylation was found to be AMPK dependent, while inhibition NF-κB was AMPK independent. In vivo, berberine also activated AMPK, inhibited mTOR and p65 phosphorylation and activated caspase-3 cleavage. Our data suggests that berberine suppresses colon epithelial proliferation and tumorigenesis via AMPK dependent inhibition of mTOR activity and AMPK independent inhibition of NF-κB.

  8. Hippocampal expression of apoptotic protease activating factor-1 following diffuse axonal injury under mild hypothermia

    Institute of Scientific and Technical Information of China (English)

    Peng Yang; Limin Zhang; Yunhe Zhang; Xifeng Zou; Qunxi Li; Yun Li; Jun Zhu; Jianmin Li; Aijun Fu; Qingjun Liu; Tong Chen; Zelin Sun; Zhiyong Zhang

    2011-01-01

    The influence of mild hypothermia on neural cell apoptosis remains poorly understood. Therefore, the present study established rat models of diffuse axonal injury (DAI) at 33 °C. Morris water maze results demonstrated significantly better learning and memory functions in DAI rats with hypothermia compared with DAI rats with normothermia. Expression of apoptotic protease activating factor-1 in the hippocampal CA1 region was significantly lower in the DAI hypothermia group compared with the DAI normothermia group. Expression of apoptotic protease activating factor-1 positively correlated with latency, but negatively correlated with platform location times and time of swimming in the quadrant area. Results suggested that post-traumatic mild hypothermia in a rat model of DAI could provide cerebral protection by attenuating expression of apoptotic protease activating factor-1.

  9. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference...... in SPF decreases between an organic and an inorganic sunscreen, assuming that the sunscreens are stable, and that the SPF decrease is time dependent if caused by absorption....

  10. Stability and biological activity evaluations of PEGylated human basic fibroblast growth factor

    OpenAIRE

    Hadadian, Shahin; Shamassebi, Dariush Norouzian; Mirzahoseini, Hasan; Shokrgozar, Mohamad Ali; Bouzari, Saeid; Sepahi, Mina

    2015-01-01

    Background: Human basic fibroblast growth factor (hBFGF) is a heparin-binding growth factor and stimulates the proliferation of a wide variety of cells and tissues causing survival properties and its stability and biological activity improvements have received much attention. Materials and Methods: In the present work, hBFGF produced by engineered Escherichia coli and purified by cation exchange and heparin affinity chromatography, was PEGylated under appropriate condition employing 10 kD pol...

  11. Erectile Dysfunction Among HIV Patients Undergoing Highly Active Antiretroviral Therapy: Dyslipidemia as a Main Risk Factor

    Directory of Open Access Journals (Sweden)

    Gustavo Romero‐Velez, MD

    2014-04-01

    Conclusions: ED is highly prevalent in HIV patients. Dyslipidemia should be considered as a risk factor for ED in HIV patients. Romero‐Velez G, Lisker‐Cervantes A, Villeda‐Sandoval CI, Sotomayor de Zavaleta M, Olvera‐Posada D, Sierra‐Madero JG, Arreguin‐Camacho LO, and Castillejos‐Molina RA. Erectile dysfunction among HIV patients undergoing highly active antiretroviral therapy: Dyslipidemia as a main risk factor. Sex Med 2014;2:24–30.

  12. Determination of factors associated with physical activity levels among adolescents attending school in Kuantan, Malaysia.

    Science.gov (United States)

    Dan, S P; Mohd, Nasir M T; Zalilah, M S

    2011-08-01

    Findings from the National Health and Morbidity Survey III (MOH, 2008) indicate a 43.7% prevalence of physical inactivity among Malaysian adults. This sedentary lifestyle can also be observed among children and adolescents. A cross-sectional study was conducted to determine factors associated with physical activity levels of four hundred, 13 year-old adolescents in Kuantan, Pahang. Data on socio-demographic, health-related, and psychosocial factors were collected using a self-administered questionnaire while physical activity level was assessed using the Physical Activity Questionnaire for Older Children (PAQ-C). About one-third of the respondents were in the low physical activity level category, 61.5% were in the moderate category and only 3.0% of the adolescents were in the high physical activity level category. Males were more physically active than females (chi2 = 23.667, p = 0.0001) with female adolescents (45.1%) twice as likely as male adolescents (22.1%) to be in the low physical activity level category. The associations between physical activity level with socio-demographic and health-related factors, perception of weight status and body parts satisfaction were not significant. However, physical activity was found to be positively correlated with physical activity self-efficacy (r = 0.496, p = 0.0001), peer influence ( r = 0.468, p = 0.0001), family influence (r = 0.298, p = 0.0001) and beliefs in physical activity outcomes (r = 0.207, p = 0.0001). Negative relationships were found between physical activity with depression (r = -0.116, p = 0.021) and body size discrepancy (r = -0.143, p < 0.01). Respoedbnts who had a better perception of their current health status were more physically active chi2 = 21.062, p = 0.0001). Multivariate analyses for the prediction of physical activity showed that physical activity self-efficacy, sex and peer influence were the most significant contributors in explaining physical activity among adolescents. Physical activity

  13. Platelet activation using electric pulse stimulation: growth factor profile and clinical implications.

    Science.gov (United States)

    Torres, Andrew S; Caiafa, Antonio; Garner, Allen L; Klopman, Steve; LaPlante, Nicole; Morton, Christine; Conway, Kenneth; Michelson, Alan D; Frelinger, Andrew L; Neculaes, V Bogdan

    2014-09-01

    Autologous platelet gel therapy using platelet-rich plasma has emerged as a promising alternative for chronic wound healing, hemostasis, and wound infection control. A critical step for this therapeutic approach is platelet activation, typically performed using bovine thrombin (BT) and calcium chloride. However, exposure of humans to BT can stimulate antibody formation, potentially resulting in severe hemorrhagic or thrombotic complications. Electric pulse stimulation using nanosecond PEFs (pulse electric fields) is an alternative, nonbiochemical platelet activation method, thereby avoiding exposure to xenogeneic thrombin and associated risks. In this study, we identified specific requirements for a clinically relevant activator instrument by dynamically measuring current, voltage, and electric impedance for platelet-rich plasma samples. From these samples, we investigated the profile of growth factors released from human platelets with electric pulse stimulation versus BT, specifically platelet-derived growth factor, transforming growth factor β, and epidermal growth factor, using commercial enzyme-linked immunosorbent assay kits. Electric pulse stimulation triggers growth factor release from platelet α-granules at the same or higher level compared with BT. Electric pulse stimulation is a fast, inexpensive, easy-to-use platelet activation method for autologous platelet gel therapy.

  14. Knee hemarthrosis after arthroscopic surgery in an athlete with low factor XIII activity

    Directory of Open Access Journals (Sweden)

    Tsujii Akira

    2012-10-01

    Full Text Available Abstract We report a thirteen-year-old tennis player with knee hemarthrosis caused by low factor XIII activity. She visited our hospital because of medial peripatellar pain for two years. Although there was no abnormal sign in X-ray or MRI, diagnostic arthroscopy was performed. It revealed some cartilage debris, medial plica and complete septum of suprapatellar plica. Removing the debris by washing out and resecting the medial plica, she could return to play tennis without perioperative symptom. Two months after the first operation, her knee got swelling without any apparent cause. Since 20 ml blood was aspirated twice and MRI revealed suprapatellar mass, we performed arthroscopy again. Suprapatellar mass was old blood clot covered with complete suprapatellar plica. Resection of suprapatellar plica and washing out blood clot were performed, and severe postoperative hemarthrosis was progressively occurred. As factor XIII level was 54% preoperatively, we diagnosed that this condition was caused by low activity level of the factor and administered factor XIII concentrates. The level got improved to 129% and then hemarthrosis gradually relieved. She had no signs of recurrence. We should keep in mind of low factor XIII activity case in case of unexplained postoperative hemarthrosis after arthroscopy because consumption of the factor might promote this condition.

  15. Knee hemarthrosis after arthroscopic surgery in an athlete with low factor XIII activity.

    Science.gov (United States)

    Tsujii, Akira; Tanaka, Yoshinari; Yonetani, Yasukazu; Shiozaki, Yoshiki; Tomiyama, Yoshiaki; Horibe, Shuji

    2012-10-02

    We report a thirteen-year-old tennis player with knee hemarthrosis caused by low factor XIII activity. She visited our hospital because of medial peripatellar pain for two years. Although there was no abnormal sign in X-ray or MRI, diagnostic arthroscopy was performed. It revealed some cartilage debris, medial plica and complete septum of suprapatellar plica. Removing the debris by washing out and resecting the medial plica, she could return to play tennis without perioperative symptom. Two months after the first operation, her knee got swelling without any apparent cause. Since 20 ml blood was aspirated twice and MRI revealed suprapatellar mass, we performed arthroscopy again. Suprapatellar mass was old blood clot covered with complete suprapatellar plica. Resection of suprapatellar plica and washing out blood clot were performed, and severe postoperative hemarthrosis was progressively occurred. As factor XIII level was 54% preoperatively, we diagnosed that this condition was caused by low activity level of the factor and administered factor XIII concentrates. The level got improved to 129% and then hemarthrosis gradually relieved. She had no signs of recurrence. We should keep in mind of low factor XIII activity case in case of unexplained postoperative hemarthrosis after arthroscopy because consumption of the factor might promote this condition.

  16. The Optimum Reaction Time, Activation Energy and Frequency Factor of Methyl Ricinoleate Nitration

    OpenAIRE

    Abdullah, Abdullah; Triyono, Triyono; Trisunaryanti, Wega; Haryadi, Winarto

    2013-01-01

    Determination of the optimum reaction time, activation energy (Ea) and frequency factor (A) of methyl ricinoleate nitration has been done. The nitration was conducted with the mole ratio of methyl ricinoleate to HNO3 of 1:15. The reaction was conducted at temperatures of 29 and 64 °C with a variation of reaction time for 10, 20, 30, 60, 90, 120, and 150 min. Determination of activation energy and frequency factor was performed in a temperature of 29, 33, 38, 44, 49, 57 and 64 °C. The results ...

  17. Production of Uricase Enzyme from Aspergillus niger and Determination of Some Factors Affecting the Activity

    OpenAIRE

    ERTAN, Figen

    1999-01-01

    This study was undertaken to obtain uricase enzyme from Aspergillus niger and also to determine the production conditions and the effects of some factors on enzyme activity. The results of the experiments, in consideration of the production of the uricase enzyme and the factors affecting the production, demonstrated that enzyme activity was maximum when the production time was 3 days at a temperature of 30ºC with the initial pH at 6.0 and inductor concentration at 0.1%. It was determined th...

  18. Prediction of mutant activity and its application in molecular design of tumor necrosis factor-a

    Institute of Scientific and Technical Information of China (English)

    唐卫东; 奚涛; 王波; 郭冬林; 徐贤秀; 朱德煦

    1997-01-01

    Two models for prediction of the activity and stability of site-directed mutagenesis on tumor necrosis factor-α are established. The models are based on straightforward structural considerations, which do not require the elaboration of site-directed mutagenesis on the protein core and the hydrophobic surface area by analyzing the properties of the mutated amino acid residues. The reliabilities of the models have been tested by analyzing the mutants of tumor necrosis factor-α (TNF-α) whose two leucine residues (L29, L157) were mutated. Based on these models, a TNF-α mutant with high activity was created by molecular design.

  19. Resonance Enhancement in Piezoresponse Force Microscopy: Maping Electromechanical Activity, Contact Stiffness, and Q-Factor

    Energy Technology Data Exchange (ETDEWEB)

    Jesse, Stephen [ORNL; Mirman, B [Suffolk University, Boston; Kalinin, Sergei V [ORNL

    2006-01-01

    Piezoresponse force microscopy (PFM) and spectroscopy of domain structure and switching dynamics at small excitation voltages require resonance enhancement of the surface displacements. The contact stiffness depends strongly on local elastic properties and topography resulting in significant variations of the resonant frequency. Moreover, the resonant response is determined both by the Q factor and the electromechanical activity. Here we develop a resonance-enhanced PFM that allows mapping of the local electromechanical activity, contact stiffness, and loss factor, thus avoiding limitations inherent to conventional frequency tracking. We anticipate that this method will be instrumental in imaging weakly piezoelectric materials and probing inelastic phenomena in ferroelectrics.

  20. Combined influence of healthy diet and active lifestyle on cardiovascular disease risk factors in adolescents.

    Science.gov (United States)

    Cuenca-García, M; Ortega, F B; Ruiz, J R; González-Gross, M; Labayen, I; Jago, R; Martínez-Gómez, D; Dallongeville, J; Bel-Serrat, S; Marcos, A; Manios, Y; Breidenassel, C; Widhalm, K; Gottrand, F; Ferrari, M; Kafatos, A; Molnár, D; Moreno, L A; De Henauw, S; Castillo, M J; Sjöström, M

    2014-06-01

    To investigate the combined influence of diet quality and physical activity on cardiovascular disease (CVD) risk factors in adolescents, adolescents (n = 1513; 12.5-17.5 years) participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence study were studied. Dietary intake was registered using a 24-h recall and a diet quality index was calculated. Physical activity was assessed by accelerometry. Lifestyle groups were computed as: healthy diet and active, unhealthy diet but active, healthy diet but inactive, and unhealthy diet and inactive. CVD risk factor measurements included cardiorespiratory fitness, adiposity indicators, blood lipid profile, blood pressure, and insulin resistance. A CVD risk score was computed. The healthy diet and active group had a healthier cardiorespiratory profile, fat mass index (FMI), triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC)/HDL-C ratio (all P ≤ 0.05). Overall, active adolescents showed higher cardiorespiratory fitness, lower FMI, TC/HDL-C ratio, and homeostasis model assessment index and healthier blood pressure than their inactive peers with either healthy or unhealthy diet (all P ≤ 0.05). Healthy diet and active group had healthier CVD risk score compared with the inactive groups (all P ≤ 0.02). Thus, a combination of healthy diet and active lifestyle is associated with decreased CVD risk in adolescents. Moreover, an active lifestyle may reduce the adverse consequences of an unhealthy diet. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Role of SIRT1 and FOXO factors in eNOS transcriptional activation by resveratrol.

    Science.gov (United States)

    Xia, Ning; Strand, Susanne; Schlufter, Frank; Siuda, Daniel; Reifenberg, Gisela; Kleinert, Hartmut; Förstermann, Ulrich; Li, Huige

    2013-08-01

    Many of the cardiovascular protective effects of resveratrol are attributable to an enhanced production of nitric oxide (NO) by the endothelial NO synthase (eNOS). Resveratrol has been shown to enhance eNOS gene expression as well as eNOS enzymatic activity. The aim of the present study was to analyze the molecular mechanisms of eNOS transcriptional activation by resveratrol. Treatment of human EA.hy 926 endothelial cells with resveratrol led to a concentration-dependent upregulation of eNOS expression. In luciferase reporter gene assay, resveratrol enhanced the activity of human eNOS promoter fragments (3500, 1600, 633 and 263bp in length, respectively), indicating that the proximal promoter region is required for resveratrol-induced eNOS transcriptional activation. Knockdown of the NAD(+)-dependent protein deacetylase sirtuin 1 (SIRT1) by siRNA prevented the upregulation of eNOS mRNA and protein by resveratrol. Forkhead box O (FOXO) transcription factors are established downstream targets of SIRT1. siRNA-mediated knockdown of FOXO1 and FOXO3a abolished the effect of resveratrol on eNOS expression, indicating the involvement of these factors. Resveratrol treatment enhanced the expression of FOXO1 and FOXO3a in EA.hy 926 cells. Reporter gene assay using promoter containing forkhead response elements showed increased FOXO factor activity by resveratrol. In electrophoretic mobility shift assay, the enhanced binding of nuclear proteins to the eNOS promoter regions by resveratrol could be blocked by antibodies against FOXO1 and FOXO3a. In conclusion, resveratrol enhances the expression and activity of FOXO transcription factors. The SIRT1/FOXO factor axis is involved in resveratrol-induced eNOS transcriptional activation.

  2. Neferine, an alkaloid from lotus seed embryo, inhibits human lung cancer cell growth by MAPK activation and cell cycle arrest.

    Science.gov (United States)

    Poornima, Paramasivan; Weng, Ching Feng; Padma, Viswanadha Vijaya

    2014-01-01

    Neferine is the major bisbenzylisoquinoline alkaloid isolated from the seed embryo of a traditional medicinal plant Nelumbo nucifera (Lotus). Epidemiological studies have revealed the therapeutic potential of lotus seed embryo. Although several mechanisms have been proposed, a clear anticancer action mechanism of neferine on lung cancer cells is still not known. Lung cancer is the most common cause of cancer death in the world, and the patients with advanced stage of nonsmall lung cancer require adjunct chemotherapy after surgical resection for the eradication of cancer cells. In this study, the effects of neferine were evaluated and characterized in A549 cells. Neferine induced apoptosis in a dose-dependent manner with the hypergeneration of reactive oxygen species, activation of MAPKs, lipid peroxidation, depletion of cellular antioxidant pool, loss of mitochondrial membrane potential, and intracellular calcium accumulation. Furthermore, neferine treatment leads to the inhibition of nuclear factor kappaB and Bcl2, upregulation of Bax and Bad, release of cytochrome C, activation of caspase cascade, and DNA fragmentation. In addition, neferine could induce p53 and its effector protein p21 and downregulation of cell cycle regulatory protein cyclin D1 thereby inducing G1 cell cycle arrest. These results suggest a novel function of neferine as an apoptosis inducer in lung cancer cells.

  3. Choline Acetyltransferase Activity in Striatum of Neonatal Rats Increased by Nerve Growth Factor

    Science.gov (United States)

    Mobley, William C.; Rutkowski, J. Lynn; Tennekoon, Gihan I.; Buchanan, Karen; Johnston, Michael V.

    1985-07-01

    Some neurodegenerative disorders may be caused by abnormal synthesis or utilization of trophic molecules required to support neuronal survival. A test of this hypothesis requires that trophic agents specific for the affected neurons be identified. Cholinergic neurons in the corpus striatum of neonatal rats were found to respond to intracerebroventricular administration of nerve growth factor with prominent, dose-dependent, selective increases in choline acetyltransferase activity. Cholinergic neurons in the basal forebrain also respond to nerve growth factor in this way. These actions of nerve growth factor may indicate its involvement in the normal function of forebrain cholinergic neurons as well as in neurodegenerative disorders involving such cells.

  4. PLCζ or PAWP: revisiting the putative mammalian sperm factor that triggers egg activation and embryogenesis.

    Science.gov (United States)

    Kashir, Junaid; Nomikos, Michail; Swann, Karl; Lai, F Anthony

    2015-05-01

    In mammals, egg activation is initiated by multiple cytosolic Ca(2+) transients (Ca(2+) oscillations) that are triggered following delivery of a putative sperm factor from the fertilizing sperm. The identity of this 'sperm factor' thus holds much significance, not only as a vital component in creating a new life, but also for its potential therapeutic and diagnostic value in human infertility. Recent data have emerged suggesting the sperm factor may be a post-acrosomal sheath WW domain-binding protein (PAWP). However, a significant body of research points to a testis-specific phospholipase C zeta (PLCζ) as the sperm factor. Herein, we examine the evidence presented in favour of PAWP in relation to PLCζ and the requisite physiological properties of the mammalian sperm factor.

  5. Specificity and structural analysis of a guinea pig transfer factor-like activity.

    Science.gov (United States)

    Dunnick, W A; Bach, F H

    1977-06-01

    A transfer factor-like activity was prepared by Sephadex G-25 chromatography of immune guinea pig leukocyte lysates. This isolated material leads to antigen-dependent migration inhibition and thymidine uptake by nonimmune lymphoid cells. Tests of the "transfer factor" from guinea pigs immunized to either ovalbumin or bovine gamma-globulin demonstrated the donor specificity of the in vitro activity. The activity is susceptible to heat (56 degrees C), alkali (0.5 M sodium hydroxide), pronase, and phosphodiesterase. The pronase susceptibility is blocked by traysylol, a protease inhibitor; the phosphodiesterase susceptibility is not bocked by traysylol. The guinea pig factor was purified further by alkaline phosphatase treatment. Sephadex G-25 chromatography, and DEAE-cellulose chromatography. The final product, active in vitro, represents about 0.03% of the cellular material absorbing 260 nm light, and contains polymerized amines and phosphate. Gel electrophoresis of the fluram-reactive components suggests a limited heterogeneity of the DEAE-cellulose-purified material. These data are consistent with the active "transfer factor" molecule including both peptide and phosphate-containing components.

  6. [Sedentary lifestyle is associated with metabolic and cardiovascular risk factors independent of physical activity].

    Science.gov (United States)

    Leiva, Ana María; Martínez, María Adela; Cristi-Montero, Carlos; Salas, Carlos; Ramírez-Campillo, Rodrigo; Díaz Martínez, Ximena; Aguilar-Farías, Nicolás; Celis-Morales, Carlos

    2017-04-01

    Sedentary behavior is a main risk factor for cardiovascular disease and mortality. To investigate the association between sedentary behavior and metabolic and cardiovascular risk factors. We assessed 322 participants aged between 18 to 65 years. Physical activity and sedentary behavior were measured with accelerometers (Actigraph®). Body mass index (BMI), waist circumference, percentage of body fat, diet and blood markers (glucose, lipid profile, insulin and HOMA-IR) were measured with standardized protocols. Thirty four percent of participants were physically inactive and spent on average 8.7 h/day on sedentary activities. Per one hour increase in sedentary behavior there were significant adverse changes in glucose (4.79 mg/dl), insulin (2.73 pmol/l), HOMA-IR (0.75), BMI (0.69 kg/m²), waist circumference (1.95 cm), fat mass (1.03%), total cholesterol (9.73 mg/dl), HDL-cholesterol (-3.50 mg/dl), LDL-cholesterol (10.7 mg/dl) and triglycerides (12.4 mg/dl). These findings were independent of main confounding factors including total physical activity, dietary factors, BMI and socio-demographics. The detrimental effect of sedentary behaviors on cardiometabolic and obesity-related traits is independent of physical activity levels. Therefore, reducing sedentary time should be targeted in the population apart from increasing their physical activity levels.

  7. Epidermal growth factor inhibits hormone- and fibroblast growth factor-induced activation of phospholipase C in rat pancreatic acini.

    Science.gov (United States)

    Stryjek-Kaminska, D; Piiper, A; Caspary, W F; Zeuzem, S

    1995-01-01

    Epidermal growth factor (EGF) inhibits cholecystokinin-octapeptide-stimulated amylase release and inositol 1,4,5-trisphosphate (1,4,5-IP3) production in isolated rat pancreatic acini. In the present study, pancreatic acini were used to investigate the effect of EGF on amylase release and 1,4,5-IP3 production induced by secretagogues that activate either phospholipase C-beta (carbachol, bombesin) or phospholipase C-gamma [basic fibroblast growth factor (bFGF)]. The results show that EGF (100 ng/ml) inhibited bombesin (0.1 nM-1 microM)-induced amylase release almost completely. Similarly, the effect of EGF on carbachol-stimulated amylase release was substantial at submaximal (0.1 microM: 44% inhibition), maximal (1 microM: 75% inhibition), and supramaximal (100 microM: 33% inhibition) carbachol concentrations. EGF reduced amylase release at submaximal bFGF concentrations (0.1 nM: 40% inhibition), but not at supramaximal bFGF concentrations (1 and 10 nM). EGF decreased the peak increase of 1,4,5-IP3 in response to bombesin and carbachol (5 s after beginning of the incubation) and bFGF (15 s after beginning of the incubation) by 81 +/- 19%, 65 +/- 15%, and 56 +/- 18%, respectively. Receptor binding characteristics for secretagogues that activate phospholipase C were not influenced by coincubation with EGF excluding heterologous transmembrane receptor modulation. These results suggest that EGF inhibits the action of phospholipase C-beta- and gamma-isoenzyme-activating secretagogues in the exocrine pancreas by a postreceptor mechanism.

  8. Influential factors of insufficient physical activity among adolescents with asthma in Taiwan.

    Directory of Open Access Journals (Sweden)

    Yu-Kuei Teng

    Full Text Available Little research has been reported concerning insufficient physical activity in Taiwanese adolescents with asthma. The aims of this paper are to compare the amount of physical activity between asthmatic and non-asthmatic adolescents in Taiwan, as well as to investigate the influential factors associated with insufficient physical activity in asthmatic adolescents.Self-reporting structured questionnaires (socio-economic status, scale of family support for physical activity, amount of physical activity and peak expiratory flow were assessed from 286 adolescents with asthma and 588 non-asthmatic adolescents in a cross-sectional design. Insufficient amount of physical activity was based on less than 300 minutes per week of moderate and vigorous physical activity.Adolescents with asthma have a greater amount of physical activity and a higher level of family support than those who are non-asthmatic. In Taiwan, adolescents with asthma, girls relative to boys, obesity relative to average weight, and low family support relative to high family support were found to be associated with insufficient physical activity.Physical activity in adolescents with asthma is insufficient especially in girls, in asthmatics with obesity, and in those with low family support. We suggest that physical activity programs should be applied to Taiwan adolescents with asthma in order to match the criteria of 300 minutes per week of moderate and vigorous physical activity, especially for girls, the obese and those with a low level of family support.

  9. Analysis of the restricting factors of laser countermeasure active detection technology

    Science.gov (United States)

    Zhang, Yufa; Sun, Xiaoquan

    2016-07-01

    The detection effect of laser active detection system is affected by various kinds of factors. In view of the application requirement of laser active detection, the influence factors for laser active detection are analyzed. The mathematical model of cat eye target detection distance has been built, influence of the parameters of laser detection system and the environment on detection range and the detection efficiency are analyzed. Various parameters constraint detection performance is simulated. The results show that the discovery distance of laser active detection is affected by the laser divergence angle, the incident angle and the visibility of the atmosphere. For a given detection range, the laser divergence angle and the detection efficiency are mutually restricted. Therefore, in view of specific application environment, it is necessary to select appropriate laser detection parameters to achieve optimal detection effect.

  10. MOTIVATIONAL FACTORS RELATED TO THE PRACTICE OF PHYSICAL ACTIVITIES OF THE ELDERLY

    Directory of Open Access Journals (Sweden)

    Agnes Navarro Cabral da Silva

    2017-01-01

    Full Text Available The aim of this study was to investigate the motivational factors for older adults to practice physical activities regularly. The sample consisted of 77 elderly of both genders, aged 55 to 90 years and who were practicing physical activities for at least a month in centers of sports and leisure in the city of Indaiatuba. The inventory IMPRAF-54 (Motivation for the Regular Practice of Physical Activity Inventory was used for data collection. This instrument covers 6 dimensions of motivation for the practice of physical activities: stress control, health, sociability, competitiveness, aesthetic and pleasure. The results showed that the main motivational factor for the elderly is health. After health, sociability, pleasure and control of stress appear tied and, finally, aesthetics and competitiveness. With these results, it is possible to know what encourages older adults to attend classes and to plan for them properly, including their interests and considering them holistically.

  11. Epidermal growth factor (EGF)-induced corneal epithelial wound healing through nuclear factor κB subtype-regulated CCCTC binding factor (CTCF) activation.

    Science.gov (United States)

    Wang, Ling; Wu, Xiaolin; Shi, Ting; Lu, Luo

    2013-08-23

    Epidermal growth factor (EGF) plays an important role in corneal epithelial migration and proliferation to improve the wound healing process. This study aimed to understand the role of NFκB in EGF-induced corneal epithelial wound healing through regulation of CTCF activity, which plays important roles in cell motility and migration to promote wound healing. The effect of NFκB p50 on corneal epithelial wound healing was investigated by comparing the eyes of wild-type and p50 knockout mice. We found that there was a significant retardation in corneal epithelial wound healing in the corneas of p50 knockout mice. Wound closure rates were measured in human corneal epithelial cells transfected with an NFκB activation-sensitive CTCF expression construct to demonstrate the effect of human CTCF expression under the control of EGF-induced NFκB activation on wound healing. EGF stimulation activated NFκB, which directly triggered the expression of the exogenous human CTCF in transfected cells and, subsequently, promoted human corneal epithelial cell motility, migration, and wound healing. Overexpression of CTCF in corneal epithelial cells and mouse corneas significantly enhanced the wound healing process. Furthermore, the effect of overexpressing NFκB p50 in corneal epithelial cells on the promotion of wound healing was abolished by knockdown of CTCF with CTCF-specific shRNA. Thus, a direct regulatory relationship between EGF-induced NFκB p50 and CTCF activation affecting corneal epithelial wound healing has been established, indicating that CTCF is, indeed, a NFκB p50-targeted and effective gene product in the core transcriptional network downstream from the growth factor-induced NFκB signaling pathway.

  12. Arginase activity in mitochondria - An interfering factor in nitric oxide synthase activity assays

    Energy Technology Data Exchange (ETDEWEB)

    Venkatakrishnan, Priya; Nakayasu, Ernesto S.; Almeida, Igor C. [Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968 (United States); Miller, R.T., E-mail: tmiller2@utep.edu [Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968 (United States)

    2010-04-09

    Previously, in tightly controlled studies, using three independent, yet complementary techniques, we refuted the claim that a mitochondrial nitric oxide synthase (mtNOS) isoform exists within pure, rat liver mitochondria (MT). Of those techniques, the NOS-catalyzed [{sup 14}C]-L-arginine to [{sup 14}C]-L-citrulline conversion assay (NOS assay) with MT samples indicated a weak, radioactive signal that was NOS-independent . Aliquots of samples from the NOS assays were then extracted with acetone, separated by high performance thin-layer chromatography (HPTLC) and exposed to autoradiography. Results obtained from these samples showed no radioactive band for L-citrulline. However, a fast-migrating, diffuse, radioactive band was observed in the TLC lanes loaded with MT samples. In this manuscript, we identify and confirm that this radioactive signal in MT samples is due to the arginase-catalyzed conversion of [{sup 14}C]-L-arginine to [{sup 14}C]-urea. The current results, in addition to reconfirming the absence of NOS activity in rat liver MT, also show the need to include arginase inhibitors in studies using MT samples in order to avoid confounding results when using NOS activity assays.

  13. FACTORES FINANCIEROS LOCALES INFLUYEN LAS ACTIVIDADES DE LOS BANCOS COOPERATIVOS GRIEGOS / LOCAL FINANCIAL FACTORS INFLUENCING ACTIVITIES OF GREEK COOPERATIVE BANKS

    Directory of Open Access Journals (Sweden)

    GEORGE KONTEOS

    2010-09-01

    Full Text Available Este artículo examina la influencia de las condiciones locales en las actividades bancarias centrandose en el caso de los 14 bancos cooperativos en Grecia durante el período 1999-2007. Estos bancos han sido seleccionados por su carácter local y en consecuencia, están más influenciadas por las condiciones locales, en comparación con los bancos con red nacional e incluso internacional. Las condiciones locales pueden ser endógenas y exógenas al banco. Las endógenas al banco es la red bancaria que se desarrolla a nivel local o regional asi como a los miembros de los bancos que son la parte principal de la clientela de estas. Una macroeconómica y exógena condición del banco es la cantidad de ahorros en la localidad donde opera. Las actividades bancarias que han sido examinadas incluyen los depósitos y los préstamos que constituyen la parte principal de las actividades bancarias de los bancos cooperativos en Grecia. El crecimiento de la red bancaria es el principal factor de aumento de las actividades del banco; el crecimiento de los miembros de las cooperativas y el aumento de las economías locales tienen una influencia positiva, pero menos importante en las actividades de los bancos cooperativos./This paper examines the influence of local conditions on banking activities focusing on the case of 14 cooperative banks in Greece for the period 1999-2007. These banks have been chosen because of their local character and consequently they are more influenced by local conditions in comparison to banks having a national and even international network. Local conditions could be endogenous and exogenous to the bank. The endogenous to the bank are the banking network developed locally or regionally, and the members of the banks who are the main part of the banks’ clientele. A macroeconomic and exogenous to the bank condition is the amount of savings in the prefecture in which the cooperative bank operates. The banking activities which have

  14. Roles of tumor necrosis factor alpha on sperm acrosin activity and acrosome reaction

    Institute of Scientific and Technical Information of China (English)

    Shu-LingBian; Guo-YiLiu; Hai-XiaWen; Shu-ZhenWang; JiangNi; WeiZhang; HuiSi

    2004-01-01

    Aim: To study the roles of tumor necrosis factor alpha (TNF-a)on the sperm acrosin activity and acrosome reaction. Methods:The sperm acrosin activity was tested by the method of BAEE/ADH Unity and the acrosome reaction by the Triple-stain technique. Results: TNF-a decreased the sperm acrosin activityand acrosome reaction (P<0.01, P<0.01, respectively);

  15. Factors affecting the thermal activation of Neosartorya fischeri in pineapple and papaya nectars

    OpenAIRE

    Slongo, Adriana Paula; Aragão,Gláucia Maria Falcão de

    2006-01-01

    In this research factors that influence the activation of Neosartorya fischeri ascospores (heating medium, temperature of production and age of the ascospores) were studied. The heating medium used was pineapple and papaya nectars at different ratios (ºBrix/acidity). Lower activation times were observed for the N. fischeri ascospores in pineapple and papaya nectars under the conditions of temperature and production age of 25ºC for 1 month and using ratios of the heating medium of 10 for pinea...

  16. Pericyte NF-κB activation enhances endothelial cell proliferation and proangiogenic cytokine secretion in vitro

    Science.gov (United States)

    LaBarbera, Katherine E; Hyldahl, Robert D; O'Fallon, Kevin S; Clarkson, Priscilla M; Witkowski, Sarah

    2015-01-01

    Pericytes are skeletal muscle resident, multipotent stem cells that are localized to the microvasculature. In vivo, studies have shown that they respond to damage through activation of nuclear-factor kappa-B (NF-κB), but the downstream effects of NF-κB activation on endothelial cell proliferation and cell–cell signaling during repair remain unknown. The purpose of this study was to examine pericyte NF-κB activation in a model of skeletal muscle damage; and use genetic manipulation to study the effects of changes in pericyte NF-κB activation on endothelial cell proliferation and cytokine secretion. We utilized scratch injury to C2C12 cells in coculture with human primary pericytes to assess NF-κB activation and monocyte chemoattractant protein-1 (MCP-1) secretion from pericytes and C2C12 cells. We also cocultured endothelial cells with pericytes that expressed genetically altered NF-κB activation levels, and then quantified endothelial cell proliferation and screened the conditioned media for secreted cytokines. Pericytes trended toward greater NF-κB activation in injured compared to control cocultures (P = 0.085) and in comparison to C2C12 cells (P = 0.079). Second, increased NF-κB activation in pericytes enhanced the proliferation of cocultured endothelial cells (1.3-fold, P = 0.002). Finally, we identified inflammatory signaling molecules, including MCP-1 and interleukin 8 (IL-8) that may mediate the crosstalk between pericytes and endothelial cells. The results of this study show that pericyte NF-κB activation may be an important mechanism in skeletal muscle repair with implications for the development of therapies for musculoskeletal and vascular diseases, including peripheral artery disease. PMID:25911453

  17. The environment and physical activity: The influence of psychosocial, perceived and built environmental factors

    Directory of Open Access Journals (Sweden)

    Bullen Chris

    2009-03-01

    Full Text Available Abstract This study sought to integrate perceived and built environmental and individual factors into the Theory of Planned Behavior (TPB model to better understand adolescents' physical activity. Methods Participants (n = 110 aged 12 to 17 years (M = 14.6 ± 1.55 were recruited from two large metropolitan high schools in Auckland, New Zealand, were included in the analysis. Participants completed measures of the revised TPB and the perceived environment. Individual factors such as ethnicity and level of deprivation were also collected. Geographical Information Systems (GIS software was used to measure the physical environment (walkability, access to physical activity facilities. Physical activity was assessed using the ActiGraph accelerometer and the Physical Activity Questionnaire for Adolescents (PAQ-A. Data from the various sources were combined to develop an integrated model integrated for statistical analysis using structural equation modeling. Results The TPB model variables (intention and perceived behavioral control explained 43% of the variance of PAQ-A. Unique and individual contributions were made by intention and PBC and home ownership of home equipment. The model explained 13% of time spent in moderate and vigorous physical activity (Actigraph. Unique and individual contribution was made by intention. Conclusion Social cognitive variables were better predictors of both subjective and objective physical activity compared to perceived environmental and built environment factors. Implications of these findings are discussed.

  18. Factors associated with participation in physical activity among adolescents in Malaysia.

    Science.gov (United States)

    Cheah, Yong Kang; Lim, Hock Kuang; Kee, Chee Cheong; Ghazali, Sumarni Mohd

    2016-11-01

    The rising prevalence of non-communicable diseases (NCDs) has become a serious public health issue. Among the multi-factorial drivers behind NCDs are modifiable health risk factors, most notably, physical inactivity. In response to the nearly global policy priority of encouraging regular participation in physical activity, the objective of the present study is to examine the factors that determine participation in physical activity among Malaysian adolescents. Nationally representative data consisting of a large sample size was used. A censored regression model was developed to estimate the likelihood of participation and time spent on physical activity. There are significant relationships between physical activity and gender, ethnicity, self-rated academic performance, maternal education, household size and time spent on physical education. The present study provides new insights into the factors affecting physical activity participation among adolescents. Specifically, self-rated excellent academic performance, household size and physical education can increase the likelihood of being physically active. Evidence of the present study implies that policy makers should pay special attention to females, Chinese, adolescents with self-rated poor academic performance and adolescents who have low maternal education.

  19. Factors contributing to extended activity times during the provision of wheeled mobility devices.

    Science.gov (United States)

    Sprigle, Stephen; De l'aune, William

    2013-05-01

    A secondary analysis was performed on data from a recent time-motion study documenting the type and duration of activities performed during the provision of wheeled mobility and seating devices. The objective of this analysis was to report factors that were most associated with activities having extended durations. Activities were categorized as occurring during the visit-preparation, pre-delivery, delivery or follow-up phases of equipment provision. Extended activities were defined as activities at or exceeding the 75th percentile, corresponding to activities exceeding 37.5 min. Logistic regression and Odd Ratio calculations were used to identify factors that were associated with extended encounters with clients. Extended activities were more likely to be associated with Group 4 power chairs, ultra-lightweight wheelchairs and seating systems comprised of a combination of technologies, such as those with postural supports or using made-to measure or custom-molded techniques. Wheelchair and seating system type were more predictive of extended activities compared to diagnostic categories. This result leads us to posit that functional needs - rather than diagnosis - impacts the duration of client encounters and the complexity of the equipment prescribed to the user. The results also indicate that more complex equipment were more likely to require extended encounters than less complex devices in their respective groupings.

  20. 24. The transcription factors and the relevant signaling pathways activated by low concentration MNNG

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Aims: To explore the transcription factors and related signal transduction pathways activated in the alkylating agents N-methyl-N'-nitro-N-nitrosoguanindine (MNNG) exposed cells which may involved in the mechanism of MNNG induced changes of gene expression, especially the elevation of DNA polymerase β expression and also the consequence of JNK kinase activation which were reported previously in this lab. Methods: Clontech Mercury pathway profiling system containing 8 different vectors in which a specific response element is located upstream from the SEAP-reporter gene were employed to detect the transcription factor activation in Vero cells treated with 0.2 μmol/L MNNG for 2 hours. Thoroughly, CREB phosphorylation, protein kinase A (PKA) and the cellular cAMP content were also assayed with PhosphoPlus CREB (ser-133) antibody kit, protein kinase assay kit and cAMP RIA kit respectively. Results: Among 8 different response elements, the expression of the reporter gene governed by the transcription factors CREB (cAMP response element binding protein), AP1 (activator protein 1), NF-κB (nuclear factor κ B) were elevated by 1.3, 1.4 and 1.3 times higber than control respectively. The level of activated CREB by Ser-133 phosphorylation was 2.08 times higher than control in cells treated with MNNG for 60 min, as measured by immunoblotting. The activity of CREB upstream kinase protein kinase A (PKA), which can phosphorylate CREB on ser-133 was also activated, and the activation peaked at 60 min (11.03±2.80 arbitrary units vs 0.86±0.43 of control). Also, cAMP levels were significantly raised after 60-minute-treatment, 1.52 times higher vs those in solvent control. Conclusion: In addition of previously reported JNK activation, we show here that low concentration alkylating agent MNNG can also activate the cAMP-PKA and NF-κB pathway. These in consequence induce the activation of transcription factors APl, CREB and NF-κB, which may related to the MNNG induced changes in

  1. Assessing Physical Activity and its Relationship to Cardiovascular Risk Factors: NHANES 2003-2006

    Directory of Open Access Journals (Sweden)

    Cao Guichan

    2011-05-01

    Full Text Available Abstract Background Levels of physical activity (PA in the general population are difficult to characterize. Historically measurement has been based on self-report, which can be subject to bias. PA monitor use has created opportunities to improve surveillance and analytic research on activity and health. The aims of the current study were to investigate the associations between objectively measured PA and cardiovascular disease risk factors and obesity. Methods Data on PA from accelerometers, demographics, blood pressure, plasma glucose and lipids, self-reported hypertension and diabetes were obtained for adults, ages 20-65, in the NHANES surveys, 2003-2006. Outcomes were assessed as levels of moderate and vigorous activity, percentage of participants meeting recommended guidelines, and the correlations between activity and cardiovascular risk factors. Accelerometry data were available on 3,370 adults. Based on standard algorithms, activity levels were extremely low in all age-gender-race/ethnic groups, with an average of only 1 bout of vigorous activity lasting longer than 1 minute/day. Results Men spent 35 minutes in moderate activity/day, women 21 minutes; >75% of this activity was accumulated in 1-minute bouts. Levels of activity declined sharply after age 50 in all groups. Negative associations were observed between minutes of combined moderate and vigorous activity and systolic blood pressure, blood glucose, diabetes, hypertension, body mass index and obesity, and a positive association was seen with HDL-cholesterol (all P ≤ 0.03, suggesting valid rank ordering of participants by activity level. Conclusion The magnitude of the gap between self-report and accelerometry activity must be a result of either a vast social acceptability bias in reporting or inaccurate measurement with accelerometry. Therefore, due to the low validity of self reported PA data for epidemiologic research, it is pertinent to encourage the use of valid, objective

  2. Brucella and Osteoarticular Cell Activation: Partners in Crime.

    Science.gov (United States)

    Giambartolomei, Guillermo H; Arriola Benitez, Paula C; Delpino, M Victoria

    2017-01-01

    Osteoarticular brucellosis is the most common presentation of human active disease although its prevalence varies widely. The three most common forms of osteoarticular involvement are sacroiliitis, spondylitis, and peripheral arthritis. The molecular mechanisms implicated in bone damage have been recently elucidated. B. abortus induces bone damage through diverse mechanisms in which TNF-α and the receptor activator of nuclear factor kappa-B ligand (RANKL)-the natural modulator of bone homeostasis are involved. These processes are driven by inflammatory cells, like monocytes/macrophages, neutrophils, Th17 CD4(+) T, and B cells. In addition, Brucella abortus has a direct effect on osteoarticular cells and tilts homeostatic bone remodeling. These bacteria inhibit bone matrix deposition by osteoblasts (the only bone cells involved in bone deposition), and modify the phenotype of these cells to produce matrix metalloproteinases (MMPs) and cytokine secretion, contributing to bone matrix degradation. B. abortus also affects osteoclasts (cells naturally involved in bone resorption) by inducing an increase in osteoclastogenesis and osteoclast activation; thus, increasing mineral and organic bone matrix resorption, contributing to bone damage. Given that the pathology induced by Brucella species involved joint tissue, experiments conducted on synoviocytes revealed that besides inducing the activation of these cells to secrete chemokines, proinflammatory cytokines and MMPS, the infection also inhibits synoviocyte apoptosis. Brucella is an intracellular bacterium that replicates preferentially in the endoplasmic reticulum of macrophages. The analysis of B. abortus-infected synoviocytes indicated that bacteria also replicate in their reticulum suggesting that they could use this cell type for intracellular replication during the osteoarticular localization of the disease. Finally, the molecular mechanisms of osteoarticular brucellosis discovered recently shed light on how the

  3. Brucella and Osteoarticular Cell Activation: Partners in Crime

    Science.gov (United States)

    Giambartolomei, Guillermo H.; Arriola Benitez, Paula C.; Delpino, M. Victoria

    2017-01-01

    Osteoarticular brucellosis is the most common presentation of human active disease although its prevalence varies widely. The three most common forms of osteoarticular involvement are sacroiliitis, spondylitis, and peripheral arthritis. The molecular mechanisms implicated in bone damage have been recently elucidated. B. abortus induces bone damage through diverse mechanisms in which TNF-α and the receptor activator of nuclear factor kappa-B ligand (RANKL)-the natural modulator of bone homeostasis are involved. These processes are driven by inflammatory cells, like monocytes/macrophages, neutrophils, Th17 CD4+ T, and B cells. In addition, Brucella abortus has a direct effect on osteoarticular cells and tilts homeostatic bone remodeling. These bacteria inhibit bone matrix deposition by osteoblasts (the only bone cells involved in bone deposition), and modify the phenotype of these cells to produce matrix metalloproteinases (MMPs) and cytokine secretion, contributing to bone matrix degradation. B. abortus also affects osteoclasts (cells naturally involved in bone resorption) by inducing an increase in osteoclastogenesis and osteoclast activation; thus, increasing mineral and organic bone matrix resorption, contributing to bone damage. Given that the pathology induced by Brucella species involved joint tissue, experiments conducted on synoviocytes revealed that besides inducing the activation of these cells to secrete chemokines, proinflammatory cytokines and MMPS, the infection also inhibits synoviocyte apoptosis. Brucella is an intracellular bacterium that replicates preferentially in the endoplasmic reticulum of macrophages. The analysis of B. abortus-infected synoviocytes indicated that bacteria also replicate in their reticulum suggesting that they could use this cell type for intracellular replication during the osteoarticular localization of the disease. Finally, the molecular mechanisms of osteoarticular brucellosis discovered recently shed light on how the

  4. Shiga toxin activates complement and binds factor H: evidence for an active role of complement in hemolytic uremic syndrome.

    Science.gov (United States)

    Orth, Dorothea; Khan, Abdul Basit; Naim, Asma; Grif, Katharina; Brockmeyer, Jens; Karch, Helge; Joannidis, Michael; Clark, Simon J; Day, Anthony J; Fidanzi, Sonja; Stoiber, Heribert; Dierich, Manfred P; Zimmerhackl, Lothar B; Würzner, Reinhard

    2009-05-15

    Infections with enterohemorrhagic Escherichia coli (EHEC) are a major cause of hemolytic uremic syndrome (HUS). Shiga toxins (Stxs), especially Stx2, are believed to represent major virulence factors of EHEC, contributing to HUS pathogenesis. Beside EHEC-associated HUS, there are hereditary atypical forms of HUS, which are mostly caused by mutations of complement regulators. The aim of the present study was to investigate whether or not complement is also involved in the pathogenesis of EHEC-induced typical HUS, by being activated either directly or indirectly by involvement of its inhibitors. Purified Stx2 markedly activated complement via the alternative pathway and was found to bind to factor H (FH), however, only when it was active. No apparent cleavage or destruction of FH was visible, and cofactor activity in fluid phase was unaffected, but clearly delayed for surface-attached FH, where it is essential for host cell protection. Binding studies using FH constructs revealed that Stx2 binds to short consensus repeats (SCRs) 6-8 and SCRs18-20, but not to SCRs16-17, i.e., to regions involved in the surface recognition function of FH. In conclusion, complement, and in particular FH, not only plays an important role in atypical HUS, but most probably also in EHEC-induced HUS.

  5. Measurement of factor v activity in human plasma using a microplate coagulation assay.

    Science.gov (United States)

    Tilley, Derek; Levit, Irina; Samis, John A

    2012-09-09

    In response to injury, blood coagulation is activated and results in generation of the clotting protease, thrombin. Thrombin cleaves fibrinogen to fibrin which forms an insoluble clot that stops hemorrhage. Factor V (FV) in its activated form, FVa, is a critical cofactor for the protease FXa and accelerator of thrombin generation during fibrin clot formation as part of prothrombinase (1, 2). Manual FV assays have been described (3, 4), but they are time consuming and subjective. Automated FV assays have been reported (5-7), but the analyzer and reagents are expensive and generally provide only the clot time, not the rate and extent of fibrin formation. The microplate platform is preferred for measuring enzyme-catalyzed events because of convenience, time, cost, small volume, continuous monitoring, and high-throughput (8, 9). Microplate assays have been reported for clot lysis (10), platelet aggregation (11), and coagulation Factors (12), but not for FV activity in human plasma. The goal of the method was to develop a microplate assay that measures FV activity during fibrin formation in human plasma. This novel microplate method outlines a simple, inexpensive, and rapid assay of FV activity in human plasma. The assay utilizes a kinetic microplate reader to monitor the absorbance change at 405 nm during fibrin formation in human plasma (Figure 1) (13). The assay accurately measures the time, initial rate, and extent of fibrin clot formation. It requires only μl quantities of plasma, is complete in 6 min, has high-throughput, is sensitive to 24-80 pM FV, and measures the amount of unintentionally activated (1-stage activity) and thrombin-activated FV (2-stage activity) to obtain a complete assessment of its total functional activity (2-stage activity - 1-stage activity). Disseminated intravascular coagulation (DIC) is an acquired coagulopathy that most often develops from pre-existing infections (14). DIC is associated with a poor prognosis and increases mortality

  6. Predicting Factors Associated with Regular Physical Activity among College Students: Applying BASNEF Model

    Directory of Open Access Journals (Sweden)

    B. Moeini

    2011-10-01

    Full Text Available Introduction & Objective: One of the important problems in modern society is people's sedentary life style. The aim of this study was to determine factors associated with regular physical activity among college students based on BASNEF model.Materials & Methods: This study was a cross-sectional study carried out on 400 students in Hamadan University of Medical Sciences. Based on the assignment among different schools, classified sampling method was chosen for data gathering using a questionnaire in three parts including: demographic information, constructs of BASNEF model, and standard international physical activity questionnaire (IPAQ. Data were analyzed by SPSS-13, and using appropriate statistical tests (Chi-square, T-test and regression. Results: Based on the results, 271 students(67.8 % had low, 124 (31% moderate ,and 5 (1.2% vigorous physical activity. There was a significant relationship (c2=6.739, df= 1, P= 0.034 between their residence and physical activity and students living in dormitory were reported to have higher level of physical activity. Behavioral intention and enabling factors from the constructs of BASNEF model were the best predictors for having physical activity in students (OR=1.215, P = 0.000 and (OR=1.119, P= 0.000 respectively.Conclusion: With regard to the fact that majority of the students did not engage in enough physical activity and enabling factors were the most effective predictors for having regular physical activity in them, it seems that providing sports facilities can promote physical activity among the students.(Sci J Hamadan Univ Med Sci 2011;18(3:70-76

  7. Procarcinogenic effects of cyclosporine A are mediated through the activation of TAK1/TAB1 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jianmin; Walsh, Stephanie B.; Verney, Zoe M. [Department of Dermatology, University of Alabama at Birmingham, AL 35294 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, Bethesda, MD (United States); Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, AL 35294 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, AL 35294 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, AL 35294 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, AL 35294 (United States)

    2011-05-13

    Research highlights: {yields} Organ transplant recipients are highly susceptible to early skin cancer development. {yields} CsA-mediated TGFB1-dependent TAK1/TAB1 signaling augments invasive tumor growth. {yields} CsA enhances accumulation of upstream kinases, ZMP, AMPK and IRAK to activate TAK1. {yields} TAK1 mediates enhanced proliferation and reduced apoptosis via CsA-dependent NF{kappa}B. -- Abstract: Cyclosporine A (CsA) is an immunosuppressive drug commonly used for maintaining chronic immune suppression in organ transplant recipients. It is known that patients receiving CsA manifest increased growth of aggressive non-melanoma skin cancers. However, the underlying mechanism by which CsA augments tumor growth is not fully understood. Here, we show that CsA augments the growth of A431 epidermoid carcinoma xenograft tumors by activating tumor growth factor {beta}-activated kinase1 (TAK1). The activation of TAK1 by CsA occurs at multiple levels by kinases ZMP, AMPK and IRAK. TAK1 forms heterodimeric complexes with TAK binding protein 1 and 2 (TAB1/TAB2) which in term activate nuclear factor {kappa}B (NF{kappa}B) and p38 MAP kinase. Transcriptional activation of NF{kappa}B is evidenced by IKK{beta}-mediated phosphorylation-dependent degradation of I{kappa}B and consequent nuclear translocation of p65. This also leads to enhancement in the expression of its transcriptional target genes cyclin D1, Bcl2 and COX-2. Similarly, activation of p38 leads to enhanced inflammation-related signaling shown by increased phosphorylation of MAPKAPK2 and which in turn phosphorylates its substrate HSP27. Activation of both NF{kappa}B and p38 MAP kinase provide mitogenic stimuli to augment the growth of SCCs.

  8. Inflammatory transcription factors as activation markers and functional readouts in immune-to-brain communication.

    Science.gov (United States)

    Rummel, Christoph

    2016-05-01

    Immune-to-brain communication pathways involve humoral mediators, including cytokines, central modulation by neuronal afferents and immune cell trafficking to the brain. During systemic inflammation these pathways contribute to mediating brain-controlled sickness symptoms including fever. Experimentally, activation of these signaling pathways can be mimicked and studied when injecting animals with pathogen associated molecular patterns (PAMPS). One central component of the brain inflammatory response, which leads, for example, to fever induction, is transcriptional activation of brain cells via cytokines and PAMPS. We and others have studied the spatiotemporal activation and the physiological significance of transcription factors for the induction of inflammation within the brain and the manifestation of fever. Evidence has revealed a role of nuclear factor (NF)κB in the initiation, signal transducer and activator of transcription (STAT)3 in the maintenance and NF-interleukin (IL)6 in the maintenance or even termination of brain-inflammation and fever. Moreover, psychological stressors, such as exposure to a novel environment, leads to increased body core temperature and genomic NF-IL6-activation, suggesting a potential use of NF-IL6-immunohistochemistry as a multimodal brain cell activation marker and a role for NF-IL6 for differential brain activity. In addition, the nutritional status, as reflected by circulating levels of the cytokine-like hormone leptin, influence immune-to-brain communication and age-dependent changes in LPS-induced fever. Overall, transcription factors remain therapeutically important targets for the treatment of brain-inflammation and fever induction during infectious/non-infectious inflammatory and psychological stress. However, the exact physiological role and significance of these transcription factors requires to be further investigated.

  9. Unwanted Sexual Activity among Peers during Early and Middle Adolescence: Incidence and Risk Factors.

    Science.gov (United States)

    Small, Stephen A.; Kerns, Donell

    1993-01-01

    Assessed incidence and risk factors of unwanted sexual activity initiated by peers for 1,149 adolescent females. Twenty percent of sample reported some type of unwanted sexual contact in past year. Over one-third of this group reported having been forced to have sexual intercourse. Boyfriends were most commonly reported perpetrators followed by…

  10. Perbedaan Kadar Platelet Activating Factor Plasma antara Penderita Demam Berdarah Dengue dan Demam Dengue

    Directory of Open Access Journals (Sweden)

    Djatnika Setiabudi

    2013-12-01

    Full Text Available Dengue virus infection can manifest as dengue fever and, more severely, as dengue hemorrhagic fever. Their pathogenesis until now is not fully understood. One of the most favorable theories stated the presence of increasing titer of pro-inflammatory mediator in severe dengue. The aim of this study was to determine the difference of plasma platelet activating factor titer between dengue hemorrhagic fever and dengue fever patients. This observational study with cross sectional design was conducted during January–February 2013. Subjects were dengue patients, 1 to 14 years old, hospitalized at Dr. Hasan Sadikin General Hospital, Bandung District Hospital (Ujungberung, and Cimahi District Hospital (Cibabat. Dengue cases were confirmed based on nonstructural-1 antigen and/or immunoglobulin M and G rapid test. Blood samples from febrile, critical and recovery phase were drawn for the examination of platelet activating factor titer using the enzyme-linked immunosorbent assay method. There were 26 dengue cases (14 as dengue fever and 12 as dengue hemorrhagic fever. Plasma platelet activating factor titer at the critical phase was significantly higher in dengue hemorrhagic fever patients [541.45 (239.30–2,449.00] pg/mL compared to dengue fever patients [289.55 (149.50–961.50] pg/mL; p=0.007. In conclusion, plasma platelet activating factor titer at the critical phase is higher in dengue hemorrhagic fever patients than in dengue fever patients.

  11. Factors of Participants and Blogs That Predict Blogging Activeness during Teaching Practice and Induction Year

    Science.gov (United States)

    Luik, Piret; Taimalu, Merle

    2016-01-01

    The blog as a type of social software has been used in education for several years, and its positive effect in the field has been asserted in many studies. This study presents the factors of participants and blogs that predict blogging activeness during teaching practice and induction year. During the teaching practice and induction year all…

  12. Cellular origin and procoagulant activity of tissue factor-exposing microparticles in cancer patients

    NARCIS (Netherlands)

    Kleinjan, A.; Berckmans, R.J.; Böing, A.N.; Sturk, A.; Büller, H.R.; Kamphuisen, P.W.; Nieuwland, R.

    2012-01-01

    Background: In patients with cancer, tissue factor-exposing microparticles (TF-exposing MP) have been associated with disease progression and thrombosis. The cellular origin and coagulant activity of TF-exposing MP, however, remain disputed. Therefore, we investigated the cellular origin of the TF-e

  13. Mini Review: Basic Physiology and Factors Influencing Exogenous Enzymes Activity in the Porcine Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Strube, Mikael Lenz; Meyer, Anne S.; Boye, Mette

    2013-01-01

    activity during intestinal transit are few, it is known that the enzymes, being protein molecules, can be negatively affected by the gastrointestinal proteolytic enzymes and the low pH in the stomach ventricle. In this review, the pH-values, endogenous proteases and other factors native to the digestive...

  14. Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

    DEFF Research Database (Denmark)

    Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.;

    2010-01-01

    Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic...

  15. Adolescents Engaging in Risky Sexual Behavior: Sexual Activity and Associated Behavioral Risk Factors in Bolivian Adolescents

    Science.gov (United States)

    Novilla, M. Lelinneth B.; Dearden, Kirk A.; Crookston, Benjamin T.; De La Cruz, Natalie; Hill, Susan; Torres, Scott B.

    2006-01-01

    This study describes the prevalence of risky sexual activities among Bolivian adolescents within the context of other behavioral factors that contribute to compromised health outcomes, unintended pregnancies, and sexually transmitted infections including HIV/AIDS. Data was collected from 576 adolescents, 13-18 years of age, from six schools in La…

  16. Factors Influencing Middle and High Schools' Active Parental Consent Return Rates

    Science.gov (United States)

    Ji, Peter Y.; Pokorny, Steven B.; Jason, Leonard A.

    2004-01-01

    The authors examined factors influencing the return rates for attempting to collect active parental consent forms from 21,123 students in the 7th through 10th grades in 41 middle and high schools. Overall return rates from middle schools were higher than from high schools. Schools that offered high levels of staff support for collecting consent…

  17. Are There Gender-Specific Risk Factors for Suicidal Activity among Patients with Schizophrenia and Depression?

    Science.gov (United States)

    Kaplan, Kalman J.; Harrow, Martin; Faull, Robert N.

    2012-01-01

    Are there gender-specific risk factors for suicidal activity among patients with schizophrenia and depression? A total of 74 schizophrenia patients (51 men, 23 women) and 77 unipolar nonpsychotic depressed patients (26 men, 51 women) from the Chicago Follow-up Study were studied prospectively at 2 years posthospitalization and again at 7.5 years.…

  18. Low Capacitive Inductors for Fast Switching Devices in Active Power Factor Correction Applications

    DEFF Research Database (Denmark)

    Hernandez Botella, Juan Carlos; Petersen, Lars Press; Andersen, Michael A. E.

    2014-01-01

    This paper examines different winding strategies for reduced capacitance inductors in active power factor correction circuits (PFC). The effect of the parasitic capacitance is analyzed from an electro magnetic compatibility (EMI) and efficiency point of views. The purpose of this work is to inves...

  19. A Comparison of Motivational Factors and Barriers to Physical Activity among Traditional versus Nontraditional College Students

    Science.gov (United States)

    Kulavic, Kimberly; Hultquist, Cherilyn N.; McLester, John R.

    2013-01-01

    Objective: To investigate the motivational factors and the barriers to physical activity (PA) in traditional college students (TS) and nontraditional college students (NTS) and determine if differences exist between these 2 groups. Participants: A total of 746 college students; 628 were TS (19.1 [plus-minus] 1.2 years), and 118 were NTS (31.2…

  20. Regular physical activity in old age. Effect on coronary heart disease risk factors and well- being.

    NARCIS (Netherlands)

    Schuit, A.J.

    1997-01-01

    Background. Regular physical activity is considered an important aspect of a healthy lifestyle. It may improve fitness, physical competence and may lower the risk of coronary heart disease (CHD). However, until now, data on the effects of regular exercise on CHD risk factors in elde

  1. Factors associated with physical activity in children and adolescents with a physical disability : a systematic review

    NARCIS (Netherlands)

    Bloemen, Manon A T; Backx, FJG; Takken, Tim; Wittink, H; Benner, Joyce; Mollema, Jurgen; de Groot, Janke F.

    2015-01-01

    AimThe aim of this review was to summarize the important factors associated with participation in physical activity in children and adolescents with physical disabilities. MethodA systematic mixed-studies review was conducted using the databases Academic Search Elite, CINAHL, The Cochrane Library, E

  2. Factors associated with physical therapists’ implementation of physical activity interventions in the Netherlands

    NARCIS (Netherlands)

    Huijg, Johanna M.; Dusseldorp, Elise; Gebhardt, Winifred A.; Verheijden, Marieke W.; Zouwe, van der Nicolette; Middelkoop, Barend J.C.; Duijzer, Geerke; Crone, Mathilde R.

    2015-01-01

    Background. Physical therapists play an important role in the promotion of physical activity (PA) and the effectiveness of PA interventions. However, little is known about the extent to which they implement PA interventions following the intervention protocol and about the factors influencing

  3. Factors associated with physical therapists’ implementation of physical activity interventions in the Netherlands

    NARCIS (Netherlands)

    Huijg, J.M.; Dusseldorp, E.; Gebhardt, W.A.; Verheijden, M.W.; Zouwe, N. van der; Middelkoop, B.J.C.; Duijzer, G.; Crone, M.R.

    2015-01-01

    Background. Physical therapists play an important role in the promotion of physical activity (PA) and the effectiveness of PA interventions. However, little is known about the extent to which they implement PA interventions following the intervention protocol and about the factors influencing their

  4. The Plasmid-Encoded Regulator Activates Factors Conferring Lysozyme Resistance on Enteropathogenic Escherichia coli Strains▿

    Science.gov (United States)

    Salinger, Nina; Kokona, Bashkim; Fairman, Robert; Okeke, Iruka N.

    2009-01-01

    We demonstrate that enhanced lysozyme resistance of enteropathogenic Escherichia coli requires the plasmid-encoded regulator, Per, and is mediated by factors outside the locus for enterocyte effacement. EspC, a Per-activated serine protease autotransporter protein, conferred enhanced resistance on nonpathogenic E. coli, and a second Per-regulated, espC-independent lysozyme resistance mechanism was identified. PMID:18997020

  5. The plasmid-encoded regulator activates factors conferring lysozyme resistance on enteropathogenic Escherichia coli strains.

    Science.gov (United States)

    Salinger, Nina; Kokona, Bashkim; Fairman, Robert; Okeke, Iruka N

    2009-01-01

    We demonstrate that enhanced lysozyme resistance of enteropathogenic Escherichia coli requires the plasmid-encoded regulator, Per, and is mediated by factors outside the locus for enterocyte effacement. EspC, a Per-activated serine protease autotransporter protein, conferred enhanced resistance on nonpathogenic E. coli, and a second Per-regulated, espC-independent lysozyme resistance mechanism was identified.

  6. A comparison between active and passive techniques for measurements of radon emanation factors

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Coto, I. [Dept. Fisica Aplicada, University of Huelva, Huelva (Spain)], E-mail: Israel.lopez@dfa.uhu.es; Mas, J.L. [Dept. de Fisica Aplicada I, E.U.P., University of Seville, Seville (Spain); San Miguel, E.G.; Bolivar, J.P. [Dept. Fisica Aplicada, University of Huelva, Huelva (Spain); Sengupta, D. [Department of Geology and Geophysics, I.I.T. Kharagpur, West Bengal (India)

    2009-05-15

    Some radon related parameters have been determined through two different techniques (passive and active) in soil and phosphogypsum samples. Emanation factors determined through these techniques show a good agreement for soil samples while for phosphogympsum samples appear large discrepancies. In this paper, these discrepancies are analyzed and explained if non-controlled radon leakages in the passive technique are taken into account.

  7. Adherence, Compliance, and Health Risk Factor Changes following Short-Term Physical Activity Interventions

    Directory of Open Access Journals (Sweden)

    Lynda H. Norton

    2015-01-01

    Full Text Available Background. Low physical activity (PA levels are associated with poor health risk factor profiles. Intervention strategies to increase PA and quantify the rate and magnitude of change in risk factors are important. Methods. Interventions were conducted over 40 days to increase PA in 736 insufficiently active (<150 min/wk PA participants using either a pedometer or instructor-led group protocol. There were a further 135 active participants as controls. Major cardiovascular and metabolic risk factors, including fitness parameters, were measured before and after intervention. Results. Adherence to the interventions was higher for the group versus pedometer participants (87.1% versus 79.8% and compliance rates for achieving sufficient levels of PA (≥150 min/wk were also higher for the group participants (95.8% versus 77.6%. Total weekly PA patterns increased by 300 and 435 minutes, for the pedometer and group participants, respectively. Improvements were found for waist girth, total cholesterol, aerobic fitness, and flexibility relative to controls. The change in vigorous PA, but not moderate PA, was a significant predictor of the change in eight of 11 risk factor variables measured. Conclusions. Rapid and dramatic increases in PA among previously insufficiently active adults can result in important health benefits.

  8. Aberrant activation of nuclear factor of activated T cell 2 in lamina propria mononuclear cells in ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Tsung-Chieh Shih; Sen-Yung Hsieh; Yi-Yueh Hsieh; Tse-Chin Chen; Chien-Yu Yeh; Chun-Jung Lin; Deng-Yn Lin; Cheng-Tang Chiu

    2008-01-01

    AIM: To investigate the role of nuclear factor of activated T cell 2 (NFAT2), the major NFAT protein in peripheral T cells, in sustained T cell activation and intractable inflammation in human ulcerative colitis (UC).METHODS: We used two-dimensional gel-electrophoresis, immunohistochemistry, double immunohistochemical staining, and confocal microscopy to inspect the expression of NFAT2 in 107, 15, 48 and 5 cases of UC, Crohn's disease (CD), non-specific colitis, and 5 healthy individuals, respectively.RESULTS: Up-regulation with profound nucleo-translocation/activation of NFAT2 of lamina propria mononuclear cells (LPMC) of colonic mucosa was found specifically in the affected colonic mucosa from patients with UC, as compared to CD or NC (P < 0.001, Kruskal-Wallis test). Nucleo-translocation/activation of NFAT2 primarily occurred in CD8+T, but was less prominent in CD4+ T cells or CD20+B cells. It was strongly associated with the disease activity, including endoscopic stage (t = 0.2145, P = 0.0281) and histologic grade (t = 0.4167, P < 0.001).CONCLUSION: We disclose for the first time the nucleo-translocation/activatin of NFAT2 in lamina propria mononuclear cells in ulcerative colitis. Activation of NFAT2 was specific for ulcerative colitis and highly associated with disease activity. Since activation of NFAT2 is implicated in an auto-regulatory positive feedback loop of sustained T-cell activation and NFAT proteins play key roles in the calcium/calcineurin signaling pathways, our results not only provide new insights into the mechanism for sustained intractable inflammation, but also suggest the calcium-calcineurin/NFAT pathway as a new therapeutic target for ulcerative colitis.

  9. Sonme Factors that Affect the Free Radical-scavenging Activity of Tea Extracts

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Some factors that affect the free radical-scavenging activety of two tea extracts were studied in vitro. It was found that concentration of tea extract or heating tea extract or treating with activated carbon and diatomite all had obvious effect on the scavenging activety of green tea extract ,but heating or treating with diaomite had less effect on the scavenging activity of black tea extract. Ascorbic acid, for having synergic effect with tea extracts, could enhance the scavenging activity of tea extracts markedly, and the contrary was cupric ion. Reducing sugars such as fructose and glucose also had some syncrgic effect to tea extracts.

  10. Zinc inhibits nuclear factor-kappa B activation and sensitizes prostate cancer cells to cytotoxic agents.

    Science.gov (United States)

    Uzzo, Robert G; Leavis, Paul; Hatch, William; Gabai, Vladimir L; Dulin, Nickolai; Zvartau, Nadezhda; Kolenko, Vladimir M

    2002-11-01

    Prostate carcinogenesis involves transformation of zinc-accumulating normal epithelial cells to malignant cells, which do not accumulate zinc. In this study, we demonstrate by immunoblotting and immunohistochemistry that physiological levels of zinc inhibit activation of nuclear factor (NF)-kappa B transcription factor in PC-3 and DU-145 human prostate cancer cells, reduce expression of NF-kappa B-controlled antiapoptotic protein c-IAP2, and activate c-Jun NH(2)-terminal kinases. Preincubation of PC-3 cells with physiological concentrations of zinc sensitized tumor cells to tumor necrosis factor (TNF)-alpha, and paclitaxel mediated cell death as defined by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. These results suggest one possible mechanism for the inhibitory effect of zinc on the development and progression of prostate malignancy and might have important consequences for the prevention and treatment of prostate cancer.

  11. Polymorphisms at activated protein C cleavage sites of factor V: Are they important in the absence of factor V Leiden?

    Directory of Open Access Journals (Sweden)

    Ehsan Kheradmand

    2017-01-01

    Full Text Available Background: Activated protein C (APC inactivates factor V (FV by cleavage of its heavy chain at Arg306, Arg506, Arg679, and Lys994. Mutational changes, which abolish APC cleavage sites, may predispose thrombosis by altering the inactivation process of FV. FV Leiden (FVL (Arg506Glu has been demonstrated as a strong risk factor for thrombosis. In the current study, we have studied whether mutations in the cleavage sites of FV for APC, not due to FVL, would have a role in presenting APC resistance (APCR and initiation of a cerebral thrombotic event.Methods: A group of 22 patients with a history of cerebral venous thrombosis (CVT, who were not carriers of FVL enrolled in the study. The patients who had conditions associated with acquired APCR were excluded from the study. APCR test was performed on the remaining 16 patients, which showed APCR in 4 plasma samples. DNA sequencing was performed on four exons of FV of APCR patients, encoding Arg306, Arg506, Arg679, and Lys994.Results: Mutations were not found within nucleotides encoding the cleavage sites; neither was found within their close upstream and downstream sequences.Conclusion: Our results show that polymorphisms affecting cleavage sites of FV other than Arg506Glu it would be less likely to be the basis for APCR and its increased thrombosis susceptibility. In addition, it emphasizes on the importance of screening for APCR in the patients diagnosed with CVT.

  12. The EDLL motif: a potent plant transcriptional activation domain from AP2/ERF transcription factors.

    Science.gov (United States)

    Tiwari, Shiv B; Belachew, Alemu; Ma, Siu Fong; Young, Melinda; Ade, Jules; Shen, Yu; Marion, Colleen M; Holtan, Hans E; Bailey, Adina; Stone, Jeffrey K; Edwards, Leslie; Wallace, Andreah D; Canales, Roger D; Adam, Luc; Ratcliffe, Oliver J; Repetti, Peter P

    2012-06-01

    In plants, the ERF/EREBP family of transcriptional regulators plays a key role in adaptation to various biotic and abiotic stresses. These proteins contain a conserved AP2 DNA-binding domain and several uncharacterized motifs. Here, we describe a short motif, termed 'EDLL', that is present in AtERF98/TDR1 and other clade members from the same AP2 sub-family. We show that the EDLL motif, which has a unique arrangement of acidic amino acids and hydrophobic leucines, functions as a strong activation domain. The motif is transferable to other proteins, and is active at both proximal and distal positions of target promoters. As such, the EDLL motif is able to partly overcome the repression conferred by the AtHB2 transcription factor, which contains an ERF-associated amphiphilic repression (EAR) motif. We further examined the activation potential of EDLL by analysis of the regulation of flowering time by NF-Y (nuclear factor Y) proteins. Genetic evidence indicates that NF-Y protein complexes potentiate the action of CONSTANS in regulation of flowering in Arabidopsis; we show that the transcriptional activation function of CONSTANS can be substituted by direct fusion of the EDLL activation motif to NF-YB subunits. The EDLL motif represents a potent plant activation domain that can be used as a tool to confer transcriptional activation potential to heterologous DNA-binding proteins.

  13. Optimization of reporter gene assay: several factors influencing detection of promoter activity

    Institute of Scientific and Technical Information of China (English)

    XUE Li-xiang; WENG Mo; ZHANG Zong-yu; TONG Tan-jun

    2007-01-01

    Background Promoter analysis is currently applied to detect the expression of the targeted gene in studies of signal transduction and transcriptional regulation. As a reporter gene, luciferase plays an important role and has been used widely in the promoter assay.Methods Human embryonic lung fibroblast cells (2BS), HeLa cells and MCF-7 cells were transfected with various genes embedded by lipofectamine. This study determined various factors that affect promoter activity determination,such as the selection of the reporter genes and internal references, the dose and the type of the vectors carrying the transcription factors, the host cells and the instruments.Results The sensitivity of the luciferase assay was much higher than that of enhanced green fluorescence protein (EGFP). Moreover, promoter activity is increased in a dose-related manner only in certain ranges outside of which the results may be reversed and the promoter activity is related to the expression vector which is carrying the cDNA.Otherwise, the length of the promoter, internal references and the host cell can also influence the promoter activity.Conclusions To detect the promoter activity accurately, a few factors including dose, vector, length and host cell which influence reporter gene assay aforementioned should be considered.

  14. Individual factors affecting preferences for feedback message tactics in the contexts of physical activity.

    Science.gov (United States)

    Hirvonen, Noora; Enwald, Heidi; Bath, Peter A; Pyky, Riitta; Korpelainen, Raija; Huotari, Maija-Leena

    2015-01-01

    Tailored feedback on personal physical activity behavior has been used to inform individuals and promote physical activity among different populations. This study aimed to increase the understanding of factors associated with young men's preferences for feedback message tactics in the context of physical activity and exercise. How preferences vary was analyzed in terms of the self-reported physical activity, stage of exercise behavior change, exercise self-efficacy, objectively measured physical health status, and sociodemographic characteristics of young Finnish men. Population-based survey data, including physiological measurements (n = 525), were collected at the Finnish Defence Forces' call-ups in the city of Oulu, Finland, in September 2011. The results indicate that the stage of exercise behavior change, exercise self-efficacy, physical health status, and educational level are associated with a preference for normative and ipsative comparison. Multivariate logistic regression models show that an advanced stage of exercise behavior change and education in the academic track of an upper secondary school are independent predictors of preferring ipsative and normative physical activity feedback among young men. The study provides new insights into how the stage of behavior change influences health information behavior and is in line with studies emphasizing social factors--including education--as being important in shaping health-related behavior. These factors could form the basis for tailoring information when designing health promotion.

  15. MiT/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5.

    Science.gov (United States)

    Nezich, Catherine L; Wang, Chunxin; Fogel, Adam I; Youle, Richard J

    2015-08-03

    The kinase PINK1 and ubiquitin ligase Parkin can regulate the selective elimination of damaged mitochondria through autophagy (mitophagy). Because of the demand on lysosomal function by mitophagy, we investigated a role for the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, in this process. We show that during mitophagy TFEB translocates to the nucleus and displays transcriptional activity in a PINK1- and Parkin-dependent manner. MITF and TFE3, homologues of TFEB belonging to the same microphthalmia/transcription factor E (MiT/TFE) family, are similarly regulated during mitophagy. Unlike TFEB translocation after starvation-induced mammalian target of rapamycin complex 1 inhibition, Parkin-mediated TFEB relocalization required Atg9A and Atg5 activity. However, constitutively active Rag guanosine triphosphatases prevented TFEB translocation during mitophagy, suggesting cross talk between these two MiT/TFE activation pathways. Analysis of clustered regularly interspaced short palindromic repeats-generated TFEB/MITF/TFE3/TFEC single, double, and triple knockout cell lines revealed that these proteins partly facilitate Parkin-mediated mitochondrial clearance. These results illuminate a pathway leading to MiT/TFE transcription factor activation, distinct from starvation-induced autophagy, which occurs during mitophagy.

  16. Elective surgery on factor VIII inhibitor patients using continuous infusion of recombinant activated factor VII: plasma factor VII activity of 10 IU/ml is associated with an increased incidence of bleeding.

    Science.gov (United States)

    Smith, M P; Ludlam, C A; Collins, P W; Hay, C R; Wilde, J T; Grigeri, A; Melsen, T; Savidge, G F

    2001-10-01

    We examined recombinant activated factor VII (rVIIa) administered by continuous infusion to eight patients with inhibitors to factor VIII, undergoing elective surgery. rVIIa was infused at a fixed rate of 16.5 microg/kg/h for a median of 13.5 days (range 1-26). There was effective haemostasis at this infusion rate in only one of two minor procedures and two of six major operations. Three patients experienced excessive bleeding despite plasma factor VII activity around 10 IU/ml. Serious bleeding occurred in two other patients caused by procedural errors unrelated to rVIIa and required re-operation. The median rVIIa clearance on day 1 was 57 ml/h/kg (range 18-100) and on day 3 was 100 ml/h/kg (range 61-200). Clearance on the final infusion day was not significantly different from day 3. The infusion did not induce pathological activation of the coagulation mechanism. The only thrombotic adverse events were two episodes of superficial thrombophlebitis of the infused vein in one subject. In conclusion, the 16.5 microg/kg/h infusion rate reliably achieves plasma factor VII activity levels of 10 IU/ml, but this level does not provide reliable haemostasis.

  17. Changes in nonnutritional factors and antioxidant activity during germination of nonconventional legumes.

    Science.gov (United States)

    Aguilera, Yolanda; Díaz, María Felicia; Jiménez, Tania; Benítez, Vanesa; Herrera, Teresa; Cuadrado, Carmen; Martín-Pedrosa, Mercedes; Martín-Cabrejas, María A

    2013-08-28

    The present study describes the effects of germination on nonnutritional factors and antioxidant activity in the nonconventional legumes Vigna unguiculata (cowpea), Canavalia ensiformis (jack bean), Lablab purpureus (dolichos), and Stizolobium niveum (mucuna). Protease inhibitors and lectins were detected in raw legumes and were significantly decreased during the germination. Regarding total and individual inositol phosphates (IP5-IP3), important reductions of IP6 and high increases in the rest of inositol phosphates were also detected during this process. In addition, total phenols, catechins, and proanthocyanidins increased, accompanied by an overall rise of antioxidant activity (79.6 μmol of Trolox/g of DW in the case of mucuna). Germination has been shown to be a very effective process to reduce nonnutritional factors and increase bioactive phenolic compounds and antioxidant activities of these nonconventional legumes. For this reason, they could be used as ingredients to obtain high-value legume flours for food formulation.

  18. Interferon and tumor necrosis factor as humoral mechanisms coupling hematopoietic activity to inflammation and injury.

    Science.gov (United States)

    Askenasy, Nadir

    2015-01-01

    Enhanced hematopoiesis accompanies systemic responses to injury and infection. Tumor necrosis factor (TNF) produced by injured cells and interferons (IFNs) secreted by inflammatory cells is a co-product of the process of clearance of debris and removal of still viable but dysfunctional cells. Concomitantly, these cytokines induce hematopoietic stem and progenitor cell (HSPC) activity as an intrinsic component of the systemic response. The proposed scenario includes induction of HSPC activity by type I (IFNα/β) and II (IFNγ) receptors within the quiescent bone marrow niches rendering progenitors responsive to additional signals. TNFα converges as a non-selective stimulant of HSPC activity and both cytokines synergize with other growth factors in promoting differentiation. These physiological signaling pathways of stress hematopoiesis occur quite frequent and do not cause HSPC extinction. The proposed role of IFNs and TNFs in stress hematopoiesis commends revision of their alleged involvement in bone marrow failure syndromes.

  19. Study of activity and effectiveness factor of noble metal catalysts for water-gas shift reaction

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sungkwang; Bae, Joongmyeon [Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology (KAIST), 373-1, Guseong-Dong, Yuseong-Gu, Daejeon 305-701 (Korea); Kim, Kihyun [POSCO 1, Goedong-dong, Nam-gu, Pohang, Gyeongbuk 790-785 (Korea)

    2009-01-15

    Platinum on ceria-zirconia (CZO) catalysts for the water-gas shift (WGS) reaction were prepared with various platinum loadings. In addition, the activity of Pt/CZO catalysts was tested preliminarily at gas hourly space velocity (GHSV) of 5000 h{sup -1}. Activity tests were also conducted at GHSV of 200,000 h{sup -1} with limited conversions, and activation energies and pre-exponential factors for rate equations were obtained by fitting the data. The effectiveness factors were estimated on the basis of the intra-particle mass transfer. Moreover, with this estimation, an attempt was made to calculate the utilization of the Pt loading with an eggshell morphology. (author)

  20. Lorentz factor distribution of blazars from the optical Fundamental plane of black hole activity

    CERN Document Server

    Saikia, Payaswini; Falcke, Heino

    2016-01-01

    Blazar radiation is dominated by a relativistic jet which can be modeled at first approximation using just two intrinsic parameters - the Lorentz factor $\\Gamma$ and the viewing angle $\\theta$. Blazar jet observations are often beamed due to relativistic effects, complicating the understanding of these intrinsic properties. The most common way to estimate blazar Lorentz factors needs the estimation of apparent jet speeds and Doppler beaming factors. We present a new and independent method of constructing the blazar Lorentz factor distribution, using the optical fundamental plane of black hole activity. The optical fundamental plane is a plane stretched out by both the supermassive black holes and the X-ray binaries, in the 3D space provided by their [OIII] line luminosity, radio luminosity and black hole mass. We use the intrinsic radio luminosity obtained from the optical fundamental plane to constrain the boosting parameters of the VLBA Imaging and Polarimetry Survey (VIPS) blazar sample. We find a blazar b...

  1. An Efficient Method to Identify Conditionally Activated Transcription Factors and their Corresponding Signal Transduction Pathway Segments

    Directory of Open Access Journals (Sweden)

    Haiyan Hu

    2009-11-01

    Full Text Available A signal transduction pathway (STP is a cascade composed of a series of signal transferring steps, which often activate one or more transcription factors (TFs to control the transcription of target genes. Understanding signaling pathways is important to our understanding of the molecular mechanisms of disease. Many condition-annotated pathways have been deposited in public databases. However, condition-annotated pathways are far from complete, considering the large number of possible conditions. Computational methods to assist in the identification of conditionally activated pathways are greatly needed. In this paper, we propose an efficient method to identify conditionally activated pathway segments starting from the identification of conditionally activated TFs, by incorporating protein-DNA binding data, gene expression data and protein interaction data. Applying our methods on several microarray datasets, we have discovered many significantly activated TFs and their corresponding pathway segments, which are supported by evidence in the literature.

  2. On involvement of transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells, activator protein-1 and signal transducer and activator of transcription-3 in photodynamic therapy-induced death of crayfish neurons and satellite glial cells

    Science.gov (United States)

    Berezhnaya, Elena; Neginskaya, Marya; Kovaleva, Vera; Sharifulina, Svetlana; Ischenko, Irina; Komandirov, Maxim; Rudkovskii, Mikhail; Uzdensky, Anatoly B.

    2015-07-01

    Photodynamic therapy (PDT) is currently used in the treatment of brain tumors. However, not only malignant cells but also neighboring normal neurons and glial cells are damaged during PDT. In order to study the potential role of transcription factors-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein (AP-1), and signal transducer and activator of transcription-3 (STAT-3)-in photodynamic injury of normal neurons and glia, we photosensitized the isolated crayfish mechanoreceptor consisting of a single sensory neuron enveloped by glial cells. Application of different inhibitors and activators showed that transcription factors NF-κB (inhibitors caffeic acid phenethyl ester and parthenolide, activator betulinic acid), AP-1 (inhibitor SR11302), and STAT-3 (inhibitors stattic and cucurbitacine) influenced PDT-induced death and survival of neurons and glial cells in different ways. These experiments indicated involvement of NF-κB in PDT-induced necrosis of neurons and apoptosis of glial cells. However, in glial cells, it played the antinecrotic role. AP-1 was not involved in PDT-induced necrosis of neurons and glia, but mediated glial apoptosis. STAT-3 was involved in PDT-induced apoptosis of glial cells and necrosis of neurons and glia. Therefore, signaling pathways that regulate cell death and survival in neurons and glial cells are different. Using various inhibitors or activators of transcription factors, one can differently influence the sensitivity and resistance of neurons and glial cells to PDT.

  3. The relationship between postnatal depression, sociodemographic factors, levels of partner support, and levels of physical activity

    Directory of Open Access Journals (Sweden)

    Maryam eSaligeh

    2014-07-01

    Full Text Available Background: postnatal depression (PND is defined as a psychological mood disorder that occurs in a mother within six weeks of her giving birth. It refers to an episode that causes mood disturbance and it could begin in, or extend into, the postpartum period. It is thought to have a high impact upon the mother’s health as well as the family’s functioning and the child’s development. Socio-demographic, psych-social, and physical activity factors may all contribute to postpartum mood and ability to cope with responsibilities. The primary aim of this study was to determine which of these factors predicted PND in postpartum women. A secondary aim was to identify the socio-demographic and psycho-social predictors of physical activity in postpartum women . Methods: The study used a cross-sectional correlational design. A sample of 150 postpartum women was sent a package of six standardised questionnaires. Results: There was no association between physical activity and PND; however, older mothers, mothers of younger children, mothers who are less reluctant to ask for help, and mothers who are more satisfied with the help they get experience lower levels of PND. Mothers of older babies, mothers with more children, and less educated mothers are more likely to engage in caregiving activities, whereas mothers with fewer children and higher levels of partner support are more likely to engage in occupational activities. None of the socio-demographic factors or any of the parenting factors predicted levels of sporting activity.

  4. Estimation the impact of macroeconomic factors on the innovation activities of enterprises in Ukraine

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    K.M. Khaustova

    2016-09-01

    Full Text Available The aim of the article. Analysis of economic processes at the macro level that determine conditions of modern innovation progress of enterprises in Ukraine, development practical recommendations for their use in strategic planning. The results of the analysis. The tendencies of innovation of domestic enterprises show their significant dependence on the macroeconomic situation and its dynamics, as evidenced by statistics. In this context, the strategic decisions on innovation require analysis and forecasting of macroeconomic factors. Based on a systematic analysis of the literature and practice of innovative management were systematized basic macro economic factors that indirectly affect the level of innovation activity of domestic enterprises with the release of the following groups: investment, financial and market. Correlation-regression analysis has revealed dependence volume of innovative products from these factors. The index method was used for the analysis of all these factors to determine their level and areas of influence on the development of innovation activity. The index method is to identify deviations of parameters of each factor from the average values for the entire period of observation As a result, determined that innovation activity of enterprises is under the influence rather turbulent macroeconomic factors. This creates a significant threat to the introduction of new technologies and the implementation of innovative projects because increases their riskiness and makes impossible calculations of ROI. The most significant barriers of innovative development are: the reduction of state support for science, technology and innovation funding, rapid and unpredictable devaluation of national money, currency restrictions and unpredictable decisions to change the NBU discount rate. Determined, that promising opportunities to enter the European market and increased domestic competition producers contributed to the emergence of some

  5. Factors influencing the measurement of lysosomal enzymes activity in human cerebrospinal fluid.

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    Emanuele Persichetti

    Full Text Available Measurements of the activities of lysosomal enzymes in cerebrospinal fluid have recently been proposed as putative biomarkers for Parkinson's disease and other synucleinopathies. To define the operating procedures useful for ensuring the reliability of these measurements, we analyzed several pre-analytical factors that may influence the activity of β-glucocerebrosidase, α-mannosidase, β-mannosidase, β-galactosidase, α-fucosidase, β-hexosaminidase, cathepsin D and cathepsin E in cerebrospinal fluid. Lysosomal enzyme activities were measured by well-established fluorimetric assays in a consecutive series of patients (n = 28 with different neurological conditions, including Parkinson's disease. The precision, pre-storage and storage conditions, and freeze/thaw cycles were evaluated. All of the assays showed within- and between-run variabilities below 10%. At -20°C, only cathepsin D was stable up to 40 weeks. At -80°C, the cathepsin D, cathepsin E, and β-mannosidase activities did not change significantly up to 40 weeks, while β-glucocerebrosidase activity was stable up to 32 weeks. The β-galactosidase and α-fucosidase activities significantly increased (+54.9±38.08% after 4 weeks and +88.94±36.19% after 16 weeks, respectively. Up to four freeze/thaw cycles did not significantly affect the activities of cathepsins D and E. The β-glucocerebrosidase activity showed a slight decrease (-14.6% after two freeze/thaw cycles. The measurement of lysosomal enzyme activities in cerebrospinal fluid is reliable and reproducible if pre-analytical factors are accurately taken into consideration. Therefore, the analytical recommendations that ensue from this study may contribute to the establishment of actual values for the activities of cerebrospinal fluid lysosomal enzymes as putative biomarkers for Parkinson's disease and other neurodegenerative disorders.

  6. Brain-derived neurotrophic factor mediates the activity-dependent regulation of inhibition in neocortical cultures.

    Science.gov (United States)

    Rutherford, L C; DeWan, A; Lauer, H M; Turrigiano, G G

    1997-06-15

    The excitability of cortical circuits is modulated by interneurons that release the inhibitory neurotransmitter GABA. In primate and rodent visual cortex, activity deprivation leads to a decrease in the expression of GABA. This suggests that activity is able to adjust the strength of cortical inhibition, but this has not been demonstrated directly. In addition, the nature of the signal linking activity to GABA expression has not been determined. Activity is known to regulate the expression of the neurotrophin brain-derived neurotrophic factor (BDNF), and BDNF has been shown to influence the phenotype of GABAergic interneurons. We use a culture system from postnatal rat visual cortex to test the hypothesis that activity is regulating the strength of cortical inhibition through the regulation of BDNF. Cultures were double-labeled against GABA and the neuronal marker MAP2, and the percentage of neurons that were GABA-positive was determined. Blocking spontaneous activity in these cultures reversibly decreased the number of GABA-positive neurons without affecting neuronal survival. Voltage-clamp analysis of inhibitory currents demonstrated that activity blockade also decreased GABA-mediated inhibition onto pyramidal neurons and raised pyramidal neuron firing rates. All of these effects were prevented by incubation with BDNF during activity blockade, but not by neurotrophin 3 or nerve growth factor. Additionally, blockade of neurotrophin signaling mimicked the effects of activity blockade on GABA expression. These data suggest that activity regulates cortical inhibition through a BDNF-dependent mechanism and that this neurotrophin plays an important role in the control of cortical excitability.

  7. Glucagon and Insulin Cooperatively Stimulate Fibroblast Growth Factor 21 Gene Transcription by Increasing the Expression of Activating Transcription Factor 4.

    Science.gov (United States)

    Alonge, Kimberly M; Meares, Gordon P; Hillgartner, F Bradley

    2017-03-31

    Previous studies have shown that glucagon cooperatively interacts with insulin to stimulate hepatic FGF21 gene expression. Here we investigated the mechanism by which glucagon and insulin increased FGF21 gene transcription in primary hepatocyte cultures. Transfection analyses demonstrated that glucagon plus insulin induction of FGF21 transcription was conferred by two activating transcription factor 4 (ATF4) binding sites in the FGF21 gene. Glucagon plus insulin stimulated a 5-fold increase in ATF4 protein abundance, and knockdown of ATF4 expression suppressed the ability of glucagon plus insulin to increase FGF21 expression. In hepatocytes incubated in the presence of insulin, treatment with a PKA-selective agonist mimicked the ability of glucagon to stimulate ATF4 and FGF21 expression. Inhibition of PKA, PI3K, Akt, and mammalian target of rapamycin complex 1 (mTORC1) suppressed the ability of glucagon plus insulin to stimulate ATF4 and FGF21 expression. Additional analyses demonstrated that chenodeoxycholic acid (CDCA) induced a 6-fold increase in ATF4 expression and that knockdown of ATF4 expression suppressed the ability of CDCA to increase FGF21 gene expression. CDCA increased the phosphorylation of eIF2α, and inhibition of eIF2α signaling activity suppressed CDCA regulation of ATF4 and FGF21 expression. These results demonstrate that glucagon plus insulin increases FGF21 transcription by stimulating ATF4 expression and that activation of cAMP/PKA and PI3K/Akt/mTORC1 mediates the effect of glucagon plus insulin on ATF4 expression. These results also demonstrate that CDCA regulation of FGF21 transcription is mediated at least partially by an eIF2α-dependent increase in ATF4 expression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Activation of platelet-activating factor receptor in SZ95 sebocytes results in inflammatory cytokine and prostaglandin E2 production.

    Science.gov (United States)

    Zhang, Qiwei; Seltmann, Holger; Zouboulis, Christos C; Travers, Jeffrey B

    2006-10-01

    Platelet-activating factor (PAF) is a group of phosphocholines with various biological effects mediated by the PAF receptor (PAF-R). Activation of the epidermal PAF-R induces the expression of inflammatory mediators, including cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)). The upregulation of COX-2 expression has been shown to be involved in sebocyte proliferation, sebaceous gland inflammation and carcinogenesis. The present study was designed to investigate whether PAF-R activation could induce the expression of COX-2 and production of PGE(2), as well as secretion of the inflammatory cytokine, interleukin-8 (IL-8), in the immortalized sebaceous gland cell line SZ95. Using calcium mobilization studies, we first confirmed that PAF can signal through PAF-R in SZ95 sebocytes. We then found that the production of IL-8 was induced following treatment with PAF-R agonist, however blocked by a specific PAF-R antagonist. Induction of COX-2 expression and increased PGE(2) production were observed in SZ95 sebocytes after PAF-R activation. Finally, it was demonstrated that the production of PGE(2), induced by PAF-R activation and mediated by COX-2 expression, was blocked following PAF-R antagonism in SZ95 sebocytes. These studies suggest that SZ95 sebocytes express functional PAF-Rs and PAF-Rs are involved in regulating the expression of inflammatory mediators, including COX-2, PGE(2) and IL-8.

  9. Practice of walking, moderate and vigorous physical activity and associated factors in first year undergraduate students

    Directory of Open Access Journals (Sweden)

    Gaia Salvador Claumann

    2014-12-01

    Full Text Available The changes that occur with the beginning of university life may interfere with the practice of physical activities by students. The aim was to investigate the association between the practice of walking, moderate and vigorous physical activities with sociodemographic factors and weight status in freshman students in the first semester of the first year of a public university in Florianopolis/SC. This study assessed198 students (86 men and 112 women. The practice of physical activities was collected with the International Physical Activity Questionnaire – IPAQ, short version. Students of human and educational sciences reported higher amounts of moderate physical activity when compared to health and exact science counterparts (p< 0.05. It was verified that male students, from higher economic status, from the health sciences, and full-time students showed higher time of practice of vigorous physical activity (p< 0.05. Significant associations were also observed between study period and walking, and between gender, scientific field and vigorous physical activity. It was concluded that the variables associated with the practice of physical activity differ according to the type and intensity of physical activity.

  10. Prevalence of Physical Activity in the United States: Behavioral Risk Factor Surveillance System, 2001

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    Barbara E. Ainsworth, PhD, MPH

    2005-03-01

    Full Text Available Introduction The health benefits of regular cardiovascular exercise are well-known. Such exercise, however, has traditionally been defined as vigorous physical activity, such as jogging, swimming, or aerobic dance. Exercise of moderate intensity also promotes health, and many U.S. adults may be experiencing the health benefits of exercise through lifestyle activities of moderate intensity, such as yard work, housework, or walking for transportation. Until recently, public health surveillance systems have not included assessments of this type of physical activity, focusing on exercise of vigorous intensity. We used an enhanced surveillance tool to describe the prevalence and amount of both moderate-intensity and vigorous-intensity physical activity among U.S. adults. Methods We analyzed data from the 2001 Behavioral Risk Factor Surveillance System, a state-based, random-digit–dialed telephone survey administered to U.S. adults aged 18 years and older (n = 82,834 men and 120,286 women. Physical activity behavior was assessed using questions designed to quantify the frequency of participation in moderate- or vigorous-intensity physical activities performed during leisure time or for household chores and transportation. Results Overall, 45% of adults (48% of men and 43% of women were active at recommended levels during nonworking hours (at least 30 minutes five or more days per week in moderate-intensity activities, equivalent to brisk walking, or at least 20 minutes three or more days per week in vigorous activities, equivalent to running, heavy yard work, or aerobic dance. Less than 16% of adults (15% of men and 17% of women reported no moderate or vigorous activity in a usual week. Conclusion Integrating surveillance of lifestyle activities into national systems is possible, and doing so may provide a more accurate representation of the prevalence of recommended levels of physical activity. These results, however, suggest that the majority of U

  11. Macroenvironmental factors including GDP per capita and physical activity in Europe.

    Science.gov (United States)

    Cameron, Adrian J; Van Stralen, Maartje M; Kunst, Anton E; Te Velde, Saskia J; Van Lenthe, Frank J; Salmon, Jo; Brug, Johannes

    2013-02-01

    Socioeconomic inequalities in physical activity at the individual level are well reported. Whether inequalities in economic development and other macroenvironmental variables between countries are also related to physical activity at the country level is comparatively unstudied. We examined the relationship between country-level data on macroenvironmental factors (gross domestic product (GDP) per capita, public sector expenditure on health, percentage living in urban areas, and cars per 1000 population) with country-level physical activity prevalence obtained from previous pan-European studies. Studies that assessed leisuretime physical activity (n = 3 studies including 27 countries in adults, n = 2 studies including 28 countries in children) and total physical activity (n = 3 studies in adults including 16 countries) were analyzed separately as were studies among adults and children. Strong and consistent positive correlations were observed between country prevalence of leisure-time physical activity and country GDP per capita in adults (average r = 0.70; all studies, P G 0.05). In multivariate analysis, country prevalence of leisure-time physical activity among adults remained associated with country GDP per capita (two of three studies) but not urbanization or educational attainment. Among school-age populations, no association was found between country GDP per capita and country prevalence of leisure-time physical activity. In those studies that assessed total physical activity (which also includes occupational and transport physical activity), no association with country GDP per capita was observed. Clear differences in national leisure-time physical activity levels throughout Europe may be a consequence of economic development. Lack of economic development of some countries in Europe may make increasing leisure-time physical activity more difficult. Further examination of the link between country GDP per capita and national physical activity levels (across

  12. Drosophila pico and its mammalian ortholog lamellipodin activate serum response factor and promote cell proliferation.

    Science.gov (United States)

    Lyulcheva, Ekaterina; Taylor, Eleanor; Michael, Magdalene; Vehlow, Anne; Tan, Shengjiang; Fletcher, Adam; Krause, Matthias; Bennett, Daimark

    2008-11-01

    MIG-10/RIAM/lamellipodin (MRL) proteins link activated Ras-GTPases with actin regulatory Ena/VASP proteins to induce local changes in cytoskeletal dynamics and cell motility. MRL proteins alter monomeric (G):filamentous (F) actin ratios, but the impact of these changes had not been fully appreciated. We report here that the Drosophila MRL ortholog, pico, is required for tissue and organismal growth. Reduction in pico levels resulted in reduced cell division rates, growth retardation, increased G:F actin ratios and lethality. Conversely, pico overexpression reduced G:F actin ratios and promoted tissue overgrowth in an epidermal growth factor (EGF) receptor (EGFR)-dependent manner. Consistently, in HeLa cells, lamellipodin was required for EGF-induced proliferation. We show that pico and lamellipodin share the ability to activate serum response factor (SRF), a transcription factor that responds to reduced G:F-actin ratios via its co-factor Mal. Genetics data indicate that mal/SRF levels are important for pico-mediated tissue growth. We propose that MRL proteins link EGFR activation to mitogenic SRF signaling via changes in actin dynamics.

  13. Drosophila Pico and Its Mammalian Ortholog Lamellipodin Activate Serum Response Factor and Promote Cell Proliferation

    Science.gov (United States)

    Lyulcheva, Ekaterina; Taylor, Eleanor; Michael, Magdalene; Vehlow, Anne; Tan, Shengjiang; Fletcher, Adam; Krause, Matthias; Bennett, Daimark

    2008-01-01

    Summary MIG-10/RIAM/lamellipodin (MRL) proteins link activated Ras-GTPases with actin regulatory Ena/VASP proteins to induce local changes in cytoskeletal dynamics and cell motility. MRL proteins alter monomeric (G):filamentous (F) actin ratios, but the impact of these changes had not been fully appreciated. We report here that the Drosophila MRL ortholog, pico, is required for tissue and organismal growth. Reduction in pico levels resulted in reduced cell division rates, growth retardation, increased G:F actin ratios and lethality. Conversely, pico overexpression reduced G:F actin ratios and promoted tissue overgrowth in an epidermal growth factor (EGF) receptor (EGFR)-dependent manner. Consistently, in HeLa cells, lamellipodin was required for EGF-induced proliferation. We show that pico and lamellipodin share the ability to activate serum response factor (SRF), a transcription factor that responds to reduced G:F-actin ratios via its co-factor Mal. Genetics data indicate that mal/SRF levels are important for pico-mediated tissue growth. We propose that MRL proteins link EGFR activation to mitogenic SRF signaling via changes in actin dynamics. PMID:19000833

  14. Expression and activity of SNAIL transcription factor during Epithelial to Mesenchymal Transition (EMT) in cancer progression.

    Science.gov (United States)

    Papiewska-Pająk, Izabela; Kowalska, Maria A; Boncela, Joanna

    2016-09-19

    Inhibition of E-cadherin gene expression by transcription factor SNAIL is known to be a crucial element of Epithelial to Mesenchymal Transition; EMT. Epigenetic regulation of E-cadherin expression is regulated by SNAIL binding to E-box sequences in the CDH1 gene promoter and recruiting enzymes belonging to repressor complexes that are directly engaged in histone modifications and DNA methylation leading to the modification of chromatin structure. SNAIL involvement in cell acquisition of invasive phenotype is based on direct suppression of tight-junction and gap junction proteins. The nuclear localization of SNAIL is required for SNAIL activity and protects this factor from proteasomal degradation in the cytoplasm. The main factor engaged in that process is GSK- 3β kinase. Expression and stability of SNAIL is regulated on the transctriptional and posttranscriptional levels by a number of signaling molecules and biological factors, for example: TGF-β, TNF-α, ILK and NFκB. The expression of SNAIL in cancer cells is also regulated by micro-RNA, mainly by miR-34. Increased expression of SNAIL, observed in many human cancers, has been correlated with increased resistance to chemio-, radio - or immunotherapy, gain of cancer stem cells features and migrative and invasive characteristics, which leads to tumor metastases. Understanding of the SNAIL's mechanism of action may lead to new treatment strategies in cancer directed to interfere with signaling pathways that either activate SNAIL or are activated by SNAIL.

  15. Neuroprotective Effects of Physical Activity on the Brain A Closer Look at Trophic Factor Signaling

    Directory of Open Access Journals (Sweden)

    Cristy ePhillips

    2014-06-01

    Full Text Available While the relationship between increased physical activity and cognitive ability hasbeen conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing numbers of individuals with cognitive impairment in the US population, a better understanding of how these factors work in aggregate to contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations.

  16. Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling.

    Science.gov (United States)

    Phillips, Cristy; Baktir, Mehmet Akif; Srivatsan, Malathi; Salehi, Ahmad

    2014-01-01

    While the relationship between increased physical activity and cognitive ability has been conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing number of individuals with cognitive impairments worldwide, a better understanding of how these factors contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations.

  17. Serum B-cell activating factor in myeloperoxiase-antineutrophil cytoplasmic antibodies-associated vasculitis.

    Science.gov (United States)

    Xin, Gang; Chen, Min; Su, Yun; Xu, Li-Xia; Zhao, Ming-Hui; Li, Kang-Sheng

    2014-07-01

    In this study, the serum B-cell activating factor belonging to tumor necrosis factor family (BAFF) levels in patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) were measured, and their clinical significance was further analyzed. One hundred twenty-one patients with MPO-AAV were enrolled in this study. Eighty-three patients had active vasculitis and 38 were in remission. Fifty-five healthy individuals were used as healthy controls. The levels of serum BAFF were assessed using commercial available enzyme-linked immunosorbent assay kits. The correlations between serum BAFF and Birmingham Vasculitis Activity Score, erythrocyte sedimentation rate and MPO-ANCA were further evaluated. The levels of serum BAFF of patients with MPO-AAV in both active (6.06±5.02 ng/mL) and remission phases (3.60±3.83 ng/mL) were significantly higher than those in healthy controls (0.87±0.31 ng/mL) (Pvasculitis were significantly higher than those in remission (PVasculitis Activity Score (r=0.320, Pvasculitis were 1.58 and 4.20 ng/mL, respectively. The levels of serum BAFF were elevated in patients with MPO-AAV and associated with disease activity, but they were not related with the levels of MPO-ANCA.

  18. By your own two feet: factors associated with active transportation in Canada.

    Science.gov (United States)

    Butler, Gregory P; Orpana, Heather M; Wiens, Alexander J

    2007-01-01

    The purpose of this study is to examine socio-demographic, geographic and physical activity correlates of walking and cycling for non-leisure purposes, i.e., to work, school, or errands, in Canada. Cross-sectional data from the Canadian Community Health Survey (CCHS) 2003 (n = 127,610) were analyzed using logistic regression to identify factors associated with active transportation. The dependent variables were walking 6+ hours per week and any cycling per week. Independent variables were based on age; marital, education, working and immigrant status; income; geographic location; smoking; and other physical activity. Age and income were associated with both walking and cycling, as was geographic location and other physical activity. The results demonstrated that, while similar, walking and cycling are associated with different factors, and that socio-demographic, geographic and health behaviour variables must be taken into consideration when modelling these transportation modes. Although walking and cycling are relatively easy means to incorporate physical activity in daily life, these results suggest that it is the young and the physically active who engage in them. This research points to a need to address barriers among those who could benefit the most from increased use of both modes of travel.

  19. Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens.

    Directory of Open Access Journals (Sweden)

    Nadine Werth

    Full Text Available BACKGROUND: Hypoxia inducible factor (HIF-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. METHODOLOGY/PRINCIPAL FINDINGS: Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i in all ex vivo in biopsies of patients suffering from skin infections, (ii in vitro using cell culture infection models and (iii in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis. CONCLUSIONS/SIGNIFICANCE: Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections.

  20. Factors influencing the adoption, implementation, and continuation of physical activity interventions in primary health care: A Delphi study

    NARCIS (Netherlands)

    Huijg, J.M.; Crone, M.R.; Verheijden, M.W.; Zouwe, N. van der; Middelkoop, B.J.; Gebhardt, W.A.

    2013-01-01

    Background: The introduction of efficacious physical activity interventions in primary health care is a complex process. Understanding factors influencing the process can enhance the development of effective introduction strategies. This Delphi study aimed to identify factors most relevant for the

  1. Soluble mediators can replace helper T cells in the activation of resting B lymphocytes: evidence for a human B cell activating factor.

    Science.gov (United States)

    Diu, A; Février, M; Moreau, J L; Gougeon, M L; Abadie, A; Thèze, J

    1988-01-01

    We were interested in studying the participation of T cell-derived soluble factors in the early steps of B cell activation. Thus supernatants containing such factors were obtained following activation of human T cell clones and their effects on isolated B cells investigated. These supernatants induced activation, blastogenesis and proliferation of purified resting human B cells. Our results strongly suggest the existence of a B cell Activating Factor (BCAF) of apparent molecular weight (m.w.) of 12,000-15,000 daltons which acts directly on resting B cells and replaces helper T cells in B cell activation.

  2. Evaluation of von Willebrand factor-cleaving protease activity in patients with thrombotic thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    高维强; 苏健; 白霞; 王兆钺; 阮长耿

    2004-01-01

    Background Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. In this study we investigated the von Willebrand factor-cleaving protease (vWF-cp) activity deficiency in patients with TTP.Methods The plasma or serum vWF-cp activity was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) by detecting the residual collagen binding activity (R-CBA) of von Willebrand factor (vWF) before and after digestion by vWF-cp. Multimers of vWF in plasma of patients with TTP were also analyzed by SDS-agarose electrophoresis. Moreover, the serum vWF-cp activities were compared between the patients with TTP and those with tumors.Results The coefficient of variation for intra-batch and inter-batch of the assay were 3.60% and 8.35%. The plasma and serum vWF-cp activity in healthy individuals were (78.79±9.17)% (n=30) and (79.47±10.78)% (n=53), respectively, while the plasma vWF-cp activity in 5 patients with TTP was markedly decreased [(21.83±19.98)%, P<0.001]. The unusually large vWF multimers were observed in two plasma samples of the patients with TTP. Although the vWF-cp activities in patients with benign and malignant tumors were also decreased (P<0.03 and P<0.001, respectively), they were relatively high in comparison with that of TTP patients (P<0.001).Conclusion Measurement of the vWF-cp activity using R-CBA is a simple and rapid method for diagnosing TTP. The vWF-cp activity in patients with TTP was markedly lower than those of patients with tumors.

  3. Dynamic, large-scale profiling of transcription factor activity from live cells in 3D culture.

    Directory of Open Access Journals (Sweden)

    Michael S Weiss

    Full Text Available BACKGROUND: Extracellular activation of signal transduction pathways and their downstream target transcription factors (TFs are critical regulators of cellular processes and tissue development. The intracellular signaling network is complex, and techniques that quantify the activities of numerous pathways and connect their activities to the resulting phenotype would identify the signals and mechanisms regulating tissue development. The ability to investigate tissue development should capture the dynamic pathway activity and requires an environment that supports cellular organization into structures that mimic in vivo phenotypes. Taken together, our objective was to develop cellular arrays for dynamic, large-scale quantification of TF activity as cells organized into spherical structures within 3D culture. METHODOLOGY/PRINCIPAL FINDINGS: TF-specific and normalization reporter constructs were delivered in parallel to a cellular array containing a well-established breast cancer cell line cultured in Matrigel. Bioluminescence imaging provided a rapid, non-invasive, and sensitive method to quantify luciferase levels, and was applied repeatedly on each sample to monitor dynamic activity. Arrays measuring 28 TFs identified up to 19 active, with 13 factors changing significantly over time. Stimulation of cells with β-estradiol or activin A resulted in differential TF activity profiles evolving from initial stimulation of the ligand. Many TFs changed as expected based on previous reports, yet arrays were able to replicate these results in a single experiment. Additionally, arrays identified TFs that had not previously been linked with activin A. CONCLUSIONS/SIGNIFICANCE: This system provides a method for large-scale, non-invasive, and dynamic quantification of signaling pathway activity as cells organize into structures. The arrays may find utility for investigating mechanisms regulating normal and abnormal tissue growth, biomaterial design, or as a

  4. Sumoylation delays the ATF7 transcription factor subcellular localization and inhibits its transcriptional activity.

    Science.gov (United States)

    Hamard, Pierre-Jacques; Boyer-Guittaut, Michaël; Camuzeaux, Barbara; Dujardin, Denis; Hauss, Charlotte; Oelgeschläger, Thomas; Vigneron, Marc; Kedinger, Claude; Chatton, Bruno

    2007-01-01

    Over the past few years, small ubiquitin-like modifier (SUMO) modification has emerged as an important regulator of diverse pathways and activities including protein localization and transcriptional regulation. We identified a consensus sumoylation motif (IKEE), located within the N-terminal activation domain of the ATF7 transcription factor and thus investigated the role of this modification. ATF7 is a ubiquitously expressed transcription factor, homologous to ATF2, that binds to CRE elements within specific promoters. This protein is able to heterodimerize with Jun or Fos proteins and its transcriptional activity is mediated by interaction with TAF12, a subunit of the general transcription factor TFIID. In the present article, we demonstrate that ATF7 is sumoylated in vitro (using RanBP2 as a E3-specific ligase) and in vivo. Moreover, we show that ATF7 sumoylation affects its intranuclear localization by delaying its entry into the nucleus. Furthermore, SUMO conjugation inhibits ATF7 transactivation activity by (i) impairing its association with TAF12 and (ii) blocking its binding-to-specific sequences within target promoters.

  5. Muscle sympathetic nerve activity and volume regulating factors in healthy pregnant and non-pregnant women.

    Science.gov (United States)

    Charkoudian, Nisha; Usselman, Charlotte W; Skow, Rachel J; Staab, Jeffery S; Julian, Colleen Glyde; Stickland, Michael K; Chari, Radha S; Khurana, Rshmi; Davidge, Sandra T; Davenport, Margie H; Steinback, Craig D

    2017-07-21

    Healthy, normotensive human pregnancies are associated with striking increases in both plasma volume and vascular sympathetic nerve activity (SNA). In non-pregnant humans, volume regulatory factors including plasma osmolality, vasopressin and the renin-angiotensin-aldosterone system have important modulatory effects on control of sympathetic outflow. We hypothesized that pregnancy would be associated with changes in the relationships between SNA (measured as muscle SNA) and volume regulating factors, including plasma osmolality, plasma renin activity and arginine vasopressin (AVP). We studied 46 healthy, normotensive young women (23 pregnant and 23 non-pregnant). We measured SNA, arterial pressure, plasma osmolality, plasma renin activity, AVP and other volume regulatory factors in resting, semi-recumbent posture. Pregnant women had significantly higher resting SNA (38 ± 12 vs. non-pregnant: 23 ± 6 bursts/minute), lower osmolality and higher plasma renin activity and aldosterone (all P pregnant] vs. 5.17 ± 2.03 [pregnant], P > 0.05). However, regression analysis detected a significant relationship between individual values for SNA and AVP in pregnant (r = 0.71, P pregnant women (r = 0.04). No relationships were found for other variables. These data suggest that the link between AVP release and resting SNA becomes stronger in pregnancy, which may contribute importantly to blood pressure regulation in healthy women during pregnancy. Copyright © 2017, American Journal of Physiology-Heart and Circulatory Physiology.

  6. Resveratrol regulates gene transcription via activation of stimulus-responsive transcription factors.

    Science.gov (United States)

    Thiel, Gerald; Rössler, Oliver G

    2017-03-01

    Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin of grapes and other fruits and plants, is a common constituent of our diet and of dietary supplements. Many health-promoting benefits have been connected with resveratrol in the treatment of cardiovascular diseases, cancer, diabetes, inflammation, neurodegeneration, and diseases connected with aging. To explain the pleiotropic effects of resveratrol, the molecular targets of this compound have to be identified on the cellular level. Resveratrol induces intracellular signal transduction pathways which ultimately lead to changes in the gene expression pattern of the cells. Here, we review the effect of resveratrol on the activation of the stimulus-responsive transcription factors CREB, AP-1, Egr-1, Elk-1, and Nrf2. Following activation, these transcription factors induce transcription of delayed response genes. The gene products of these delayed response genes are ultimately responsible for the changes in the biochemistry and physiology of resveratrol-treated cells. The activation of stimulus-responsive transcription factors may explain many of the intracellular activities of resveratrol. However, results obtained in vitro may not easily be transferred to in vivo systems.

  7. Leukotriene B(4) inhibits neutrophil apoptosis via NADPH oxidase activity: redox control of NF-κB pathway and mitochondrial stability.

    Science.gov (United States)

    Barcellos-de-Souza, Pedro; Canetti, Cláudio; Barja-Fidalgo, Christina; Arruda, Maria Augusta

    2012-10-01

    Leukotriene B(4), an arachidonic acid-derived lipid mediator, is a known proinflammatory agent that has a direct effect upon neutrophil physiology, inducing reactive oxygen species generation by the NADPH oxidase complex and impairing neutrophil spontaneous apoptosis, which in turn may corroborate to the onset of chronic inflammation. Despite those facts, a direct link between inhibition of neutrophil spontaneous apoptosis and NADPH oxidase activation by leukotriene B(4) has not been addressed so far. In this study, we aim to elucidate the putative role of NADPH oxidase-derived reactive oxygen species in leukotriene B(4)-induced anti-apoptotic effect. Our results indicate that NADPH oxidase-derived reactive oxygen species are critical to leukotriene B(4) pro-survival effect on neutrophils. This effect also relies on redox modulation of nuclear factor kappaB signaling pathway. We have also observed that LTB(4)-induced Bad degradation and mitochondrial stability require NADPH oxidase activity. All together, our results strongly suggest that LTB(4)-induced anti-apoptotic effect in neutrophils occurs in a reactive oxygen species-dependent manner. We do believe that a better knowledge of the molecular mechanisms underlying neutrophil spontaneous apoptosis may contribute to the development of more successful strategies to control chronic inflammatory conditions such as rheumatoid arthritis. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Factor XII-independent activation of the bradykinin-forming cascade

    DEFF Research Database (Denmark)

    Joseph, Kusumam; Tholanikunnel, Baby G; Bygum, Anette

    2013-01-01

    and assayed for kallikrein formation. C1-INH was removed from factor XII-deficient plasma by means of immunoadsorption. RESULTS: We demonstrate that prekallikrein-HK will activate to kallikrein in phosphate-containing buffers and that the rate is further accelerated on addition of heat shock protein 90....... Prolonged incubation of plasma deficient in both factor XII and C1-INH led to conversion of prekallikrein to kallikrein and cleavage of HK, as was seen in plasma from patients with hereditary angioedema but not plasma from healthy subjects. CONCLUSIONS: These results indicate that C1-INH stabilizes...

  9. Insulin-like growth factor binding protein-3 affects osteogenic efficacy on dental implants in rat mandible

    Energy Technology Data Exchange (ETDEWEB)

    Bhattarai, Govinda; Lee, Young-Hee [Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Lee, Min-Ho [Department of Dental Materials, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Park, Il-Song [Division of Advanced Materials Engineering, Research Center for Advanced Materials, Development and Institute of Biodegradable Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Yi, Ho-Keun, E-mail: yihokn@chonbuk.ac.kr [Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of)

    2015-10-01

    Insulin like growth factor binding protein-3 (IGFBP-3) in bone cells and its utilization in dental implants have not been well studied. The aim of this study was to determine the osteogenic efficacy of chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 coated titanium (Ti) implants. Ch-GNPs were conjugated with IGFBP-3 plasmid DNA through a coacervation process. Conjugation was cast over Ti surfaces, and cells were seeded on coated surfaces. For in vitro analysis the expression of different proteins was analyzed by immunoblotting. For in vivo analysis, Ch-GNP/IGFBP-3 coated implants were installed in rat mandibles. Four weeks post-implantation, mandibles were examined by microcomputed tomography (μCT), immunohistochemistry, hematoxylin & eosin and tartrate resistance acid phosphatase staining. In vitro overexpressed Ch-GNP/IGFBP-3 coated Ti surfaces was associated with activation of extracellular signal related kinase (ERK), inhibition of the stress activated protein c-Jun N-terminal kinase (JNK) and enhanced bone morphogenetic protein (BMP)-2 and 7 compared to control. Further, in vivo, Ch-GNP/IGFBP-3 coated implants were associated with inhibition of implant induced osteoclastogenesis molecules, receptor activator of nuclear factor kappa-B ligand (RANKL) and enhanced expression of osteogenic molecules including BMP2/7 and osteopontin (OPN). The μCT analysis demonstrated that IGFBP-3 increased the volume of newly formed bone surrounding the implants compared to control (n = 5; p < 0.05). These results support the view that IGFBP-3 overexpression diminishes osteoclastogenesis and enhances osteogenesis of Ti implants, and can serve as a potent molecule for the development of good implantation. - Highlights: • Chitosan gold nanoparticles were conjugated with IGFBP-3 and coated onto surface of the titanium implants for gene delivery to bone. • Implants were inserted in rat mandible for 4 weeks. • Parameters studied: histopathology and radiology.

  10. The impact of physical activity on cumulative cardiovascular disease risk factors among Malaysian adults.

    Science.gov (United States)

    Rasiah, Rajah; Thangiah, Govindamal; Yusoff, Khalid; Manikam, Rishya; Chandrasekaran, Sankara Kumar; Mustafa, Rujhan; Bakar, Najmin Binti Abu

    2015-12-16

    Numerous studies have shown the importance of physical activity in reducing the morbidity and mortality rates caused by cardiovascular disease (CVD). However, most of these studies emphasise little on the cumulative effect of CVD risk factors. Hence, this study investigates the association between physical exercise and cumulative CVD risk factors among adults in three different age groups. Using a sample of 7276 respondents drawn from community centers, the REDISCOVER team gathered information on physical activity, CVD risk factors (obesity, diabetes, hypertension, hypercholesterolemia, tobacco use) and socioeconomic and demographic variables in Malaysia. Because the study required medical examination, a convenience sampling frame was preferred in which all volunteers were included in the study. Fasting blood samples and anthropometric (height, weight and more) measurements were collected by trained staffs. Socio-demographic and physical activity variables were recorded through questionnaires. A Chi-square test was performed to identify the bivariate association between the covariates (socioeconomic variables, demographic variables and physical activity) and outcome variable. The association between the main exposure, physical activity, and the outcome variable, cumulative CVD risk factors, was assessed using an ordinal logistic regression model, controlling for socioeconomic status and demographic influences in three different age groups, 35-49, 50-64 and 65 and above. The mean age of participants is 51.8 (SD = 9.4). Respondents in the age groups of 35-49 (aORmoderate = 0.12; 95 % CI: 0.02 - 0.53 ) and 65 and above (aORhigh = 0.58; 95 % CI: 0.24, 0.78) showed a statistically significant inverse relationship between physical activity and cumulative CVD risk factors. However, this relationship was not significant among respondents in the 50-64 age group suggesting the possible influence of other variables, such as stress and environment. The

  11. Plants contain a novel multi-member class of heat shock factors without transcriptional activator potential.

    Science.gov (United States)

    Czarnecka-Verner, E; Yuan, C X; Scharf, K D; Englich, G; Gurley, W B

    2000-07-01

    Based on phylogeny of DNA-binding domains and the organization of hydrophobic repeats, two families of heat shock transcription factors (HSFs) exist in plants. Class A HSFs are involved in the activation of the heat shock response, but the role of class B HSFs is not clear. When transcriptional activities of full-length HSFs were monitored in tobacco protoplasts, no class B HSFs from soybean or Arabidopsis showed activity under control or heat stress conditions. Additional assays confirmed the finding that the class B HSFs lacked the capacity to activate transcription. Fusion of a heterologous activation domain from human HSF1 (AD2) to the C-terminus of GmHSFB1-34 gave no evidence of synergistic enhancement of AD2 activity, which would be expected if weak activation domains were present. Furthermore, activity of AtHSFB1-4 (class B) was not rescued by coexpression with AtHSFA4-21 (class A) indicating that the class A HSF was not able to provide a missing function required for class B activity. The transcriptional activation potential of Arabidopsis AtHSFA4-21 was mapped primarily to a 39 amino acid fragment in the C-terminus enriched in bulky hydrophobic and acidic residues. Deletion mutagenesis of the C-terminal activator regions of tomato and Arabidopsis HSFs indicated that these plant HSFs lack heat-inducible regulatory regions analogous to those of mammalian HSF1. These findings suggest that heat shock regulation in plants may differ from metazoans by partitioning negative and positive functional domains onto separate HSF proteins. Class A HSFs are primarily responsible for stress-inducible activation of heat shock genes whereas some of the inert class B HSFs may be specialized for repression, or down-regulation, of the heat shock response.

  12. [Evaluation and characterization of the certified reference materials for coagulation factor Ⅷ and Ⅸ activity testing].

    Science.gov (United States)

    Zhang, H P; Zhou, W B; Li, C B; Du, Z L; Peng, M T

    2016-05-31

    To evaluate and characterize the certified reference materials for coagulation factor Ⅷ (FⅧ) and factor Ⅸ (FⅨ) activity testing. The homogeneity and stability of three lots of certified reference materials (F01-F03) with different factor concentrations were evaluated according to guidelines"Reference materials-general and statistical principles for certification","Guidance on evaluating the homogeneity and stability of samples used for proficiency testing"and"Technical Norm of Primary Reference Material". The certified reference materials were characterized by eight laboratories using one-stage method, which were calibrated by the coagulation standard provided by the National Institute for Biological Standards and Control (NIBSC) in UK. The Coefficient of Variation (CV) of homogeneity test of FⅧ activity of three lots of certified reference materials were 3.9%, 3.3% and 3.4%, respectively. While that of FⅨ activity were 3.7%, 3.0% and 1.8%, respectively. The results of one-way ANOVA showed that all certified reference materials had good homogeneity (P>0.05), and the between-bottle homogeneity uncertainties (ubb) of FⅧ and FⅨ activity were 0.5%-2.9% and 0.1%-3.9%, respectively. All certified reference materials stored in -80 ℃ remained stable in 9 months by trend analysis, and the long-term stability uncertainties(ults) of FⅧ and FⅨ activity were 0.5%-5.1% and 1.3%-4.4%, respectively. The characterization uncertainties (uchar) of FⅧ and FⅨ activity testing were 0.9%-2.4% and 1.1%-2.4%, respectively. The combined uncertainties and extended uncertainties (coverage factor k=2) were calculated. The assigned values of each lot of certified reference materials for FⅧ activity were (85±13)%, (36.0±3.4)% and (20.5±2.3)%, and that were (102±13)%, (47.8±6.9)% and (29.3±3.8)% for FⅨ activity, respectively. The certified reference materials for FⅧ and FⅨ activity testing have good homogeneity and stability. The results of the

  13. Diarctigenin, a lignan constituent from Arctium lappa, down-regulated zymosan-induced transcription of inflammatory genes through suppression of DNA binding ability of nuclear factor-kappaB in macrophages.

    Science.gov (United States)

    Kim, Byung Hak; Hong, Seong Su; Kwon, Soon Woo; Lee, Hwa Young; Sung, Hyeran; Lee, In-Jeong; Hwang, Bang Yeon; Song, Sukgil; Lee, Chong-Kil; Chung, Daehyun; Ahn, Byeongwoo; Nam, Sang-Yoon; Han, Sang-Bae; Kim, Youngsoo

    2008-11-01

    Diarctigenin was previously isolated as an inhibitor of nitric oxide (NO) production in macrophages from the seeds of Arctium lappa used as an alternative medicine for the treatment of inflammatory disorders. However, little is known about the molecular basis of these effects. Here, we demonstrated that diarctigenin inhibited the production of NO, prostaglandin E(2), tumor necrosis factor-alpha, and interleukin (IL)-1beta and IL-6 with IC(50) values of 6 to 12 miciroM in zymosan- or lipopolysaccharide-(LPS) activated macrophages. Diarctigenin attenuated zymosan-induced mRNA synthesis of inducible NO synthase (iNOS) and also inhibited promoter activities of iNOS and cytokine genes in the cells. Because nuclear factor (NF)-kappaB plays a pivotal role in inflammatory gene transcription, we next investigated the effect of diarctigenin on NF-kappaB activation. Diarctigenin inhibited the transcriptional activity and DNA binding ability of NF-kappaB in zymosan-activated macrophages but did not affect the degradation and phosphorylation of inhibitory kappaB (IkappaB) proteins. Moreover, diarctigenin suppressed expression vector NF-kappaB p65-elicited NF-kappaB activation and also iNOS promoter activity, indicating that the compound could directly target an NF-kappa-activating signal cascade downstream of IkappaB degradation and inhibit NF-kappaB-regulated iNOS expression. Diarctigenin also inhibited the in vitro DNA binding ability of NF-kappaB but did not affect the nuclear import of NF-kappaB p65 in the cells. Taken together, diarctigenin down-regulated zymosan- or LPS-induced inflammatory gene transcription in macrophages, which was due to direct inhibition of the DNA binding ability of NF-kappaB. Finally, this study provides a pharmacological potential of diarctigenin in the NF-kappaB-associated inflammatory disorders.

  14. Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF.

    Science.gov (United States)

    Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

    2008-07-01

    Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years.

  15. Activated alveolar epithelial cells initiate fibrosis through autocrine and paracrine secretion of connective tissue growth factor.

    Science.gov (United States)

    Yang, Jibing; Velikoff, Miranda; Canalis, Ernesto; Horowitz, Jeffrey C; Kim, Kevin K

    2014-04-15

    Fibrogenesis involves a pathological accumulation of activated fibroblasts and extensive matrix remodeling. Profibrotic cytokines, such as TGF-β, stimulate fibroblasts to overexpress fibrotic matrix proteins and induce further expression of profibrotic cytokines, resulting in progressive fibrosis. Connective tissue growth factor (CTGF) is a profibrotic cytokine that is indicative of fibroblast activation. Epithelial cells are abundant in the normal lung, but their contribution to fibrogenesis remains poorly defined. Profibrotic cytokines may activate epithelial cells with protein expression and functions that overlap with the functions of active fibroblasts. We found that alveolar epithelial cells undergoing TGF-β-mediated mesenchymal transition in vitro were also capable of activating lung fibroblasts through production of CTGF. Alveolar epithelial cell expression of CTGF was dramatically reduced by inhibition of Rho signaling. CTGF reporter mice demonstrated increased CTGF promoter activity by lung epithelial cells acutely after bleomycin in vivo. Furthermore, mice with lung epithelial cell-specific deletion of CTGF had an attenuated fibrotic response to bleomycin. These studies provide direct evidence that epithelial cell activation initiates a cycle of fibrogenic effector cell activation during progressive fibrosis. Therapy targeted at epithelial cell production of CTGF offers a novel pathway for abrogating this progressive cycle and limiting tissue fibrosis.

  16. Effects of calmodulin on DNA-binding activity of heat shock transcription factor in vitro

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The DNA-binding activity of heat shock transcription factor (HSF) was induced by heat shock (HS) of a whole cell extract. Addition of antiserum, specific to CaM, to a whole cell extract reduced bind of the HSF to the heat shock element (HSE) with maize, and the re-addition of CaM to the sample restored the activity of the HSF for binding to HSE. In addition, DNA-binding activity of the HSF was also induced by directly adding CaM to a whole cell extract at non-HS temperature with maize. Similar results were obtained with wheat and tomato. Our observations provide the first example of the involvement of CaM in regulation of the DNA-binding activity of the HSF.

  17. Factors affecting release of ethanol vapour in active modified atmosphere packaging systems for horticultural products

    Directory of Open Access Journals (Sweden)

    Weerawate Utto

    2014-04-01

    Full Text Available The active modified atmosphere packaging (active MAP system , which provides interactive postharvest control , using ethanol vapour controlled release, is one of the current interests in the development of active packaging for horticultural products. A number of published research work have discussed the relationship between the effectiveness of ethanol vapour and its concentration in the package headspace, including its effect on postharvest decay and physiological controls. This is of importance because a controlled release system should release and maintain ethanol vapour at effective concentrations during the desired storage period. A balance among the mass transfer processes of ethanol vapour in the package results in ethanol vapour accumulation in the package headspace. Key factors affecting these processes include ethanol loading, packaging material, packaged product and storage environment (temperature and relative h umidity. This article reviews their influences and discusses future work required to better understand their influences on ethanol vapour release and accumulations in active MAP.

  18. Resveratrol Reactivates Latent HIV through Increasing Histone Acetylation and Activating Heat Shock Factor 1.

    Science.gov (United States)

    Zeng, Xiaoyun; Pan, Xiaoyan; Xu, Xinfeng; Lin, Jian; Que, Fuchang; Tian, Yuanxin; Li, Lin; Liu, Shuwen

    2017-06-07

    The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under cotreatment with resveratrol and conventional LRAs. Collectively, this research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.

  19. Temperature: a prolonged confounding factor on cholinesterase activity in the tropical reef fish Acanthochromis polyacanthus.

    Science.gov (United States)

    Botté, Emmanuelle S; Smith-Keune, Carolyn; Jerry, Dean R

    2013-09-15

    Cholinesterase activity usually decreases in fish exposed to anticholinesterase compounds such as organophosphate and carbamate pesticides. Here we show that tropical reef fish Acanthochromis polyacanthus (or spiny damsel) also exhibits a decrease in ChE activity when exposed to elevated temperature from 28°C to 32°C or 34°C after 4 days. We further demonstrate that the decline persists even after 7 days of recovery at control temperature. This is the first report of a drop in ChE activity in fish as temperature increases. Our results strongly suggest the need for long-term monitoring of water temperature in the field prior to sampling A. polyacanthus for toxicology studies, as temperature is a prolonged and confounding factor for ChE activity in this species.

  20. Danger signal-dependent activation of human dendritic cells by plasma-derived factor VIII products.

    Science.gov (United States)

    Miller, L; Weissmüller, S; Ringler, E; Crauwels, P; van Zandbergen, G; Seitz, R; Waibler, Z

    2015-08-01

    Treatment of haemophilia A by infusions of the clotting factor VIII (FVIII) results in the development of inhibitors/anti-drug antibodies in up to 25 % of patients. Mechanisms leading to immunogenicity of FVIII products are not yet fully understood. Amongst other factors, danger signals as elicited upon infection or surgery have been proposed to play a role. In the present study, we focused on effects of danger signals on maturation and activation of dendritic cells (DC) in the context of FVIII application. Human monocyte-derived DC were treated with FVIII alone, with a danger signal alone or a combination of both. By testing more than 60 different healthy donors, we show that FVIII and the bacterial danger signal lipopolysaccharide synergise in increasing DC activation, as characterised by increased expression of co-stimulatory molecules and secretion of pro-inflammatory cytokines. The degree and frequency of this synergistic activation correlate with CD86 expression levels on immature DC prior to stimulation. In our assay system, plasma-derived but not recombinant FVIII products activate human DC in a danger signal-dependent manner. Further tested danger signals, such as R848 also induced DC activation in combination with FVIII, albeit not in every tested donor. In our hands, human DC but not human B cells or macrophages could be activated by FVIII in a danger signal-dependent manner. Our results suggest that immunogenicity of FVIII is a result of multiple factors including the presence of danger, predisposition of the patient, and the choice of a FVIII product for treatment.

  1. The Activities and Culture of Teachers: the Interdependent Factors of Their Development

    Directory of Open Access Journals (Sweden)

    Alexander Mishchenko

    2017-09-01

    Full Text Available The object of the experimental research is teachers of the vocational schools and colleges of Saint Petersburg. 583 teachers were questioned on experiment. Authors’ positional and semantic paradigm of the research was established, which allows us to fully explore the very pinch of its activity and professional culture. We analyzed factors, which are closely connected with the development of the content of the activity and professional culture of the teaching stuff. The subject of the sociological research is social, educational (organizational and personal factors of development of teacher’s activity and professional development as subjects of the education. The main research method is correlation and statistical analysis of sociological survey data, taken by author’s multi-criteria modular type form. In the paper, the educational organization is shown as crossing field of social and economical, organizational and personal factors of development of teacher’s activity and professional development. They show multidiscipline (social, economical, organizational, competence-based and personal aspects of intercommunion of activity and professional development of the subjects of education. Thereupon we conclude, that intercommunions of this facts, peculiar to teachers of the vocational schools and colleges, can be learned in a consistent manner only on the ground of studying: regularities of productive labour, as the expression of the system of social and economical relations in society; tendencies in the development of the secondary vocational education system; modernization process of educational institution of the secondary vocational education; the evolution of relation system between teachers and pupils in educational institution; teacher’s personality as subject of the education process. These aspects of the scientific analysis allow to cover the intercommunion of activity and professional culture of the teaching stuff in the context of

  2. Innovation activity of scientists as a factor in the development of academic entrepreneurship in Russia

    Directory of Open Access Journals (Sweden)

    L. N. Babak

    2016-01-01

    Full Text Available The development of academic entrepreneurship as a way of transfer of innovation is an urgent task. One of the main factors in the development of academic entrepreneurship is innovation-oriented staff of higher education institutions. Insufficient attention of the scientific literature to importance of this factor is thwarting progress of various forms of academic entrepreneurship. In connection with this proposed study is aimed at determining the degree of scientific innovation activity influence on the development of academic entrepreneurship in Russia. Academic entrepreneurship in Russia has been chosen as the object of study. Analysis of the basic research in the field of academic entrepreneurship for the period of 2011-2016 years was used to achieve this goal. Analysis of publications was revealed that the innovative activity of the teaching staff of universities is a critical factor in the development of academic entrepreneurship. However, Russian scientists are characterized by low innovation activity, resulting in academic entrepreneurship in Russia is weak. The researchers suggest the following solutions to eliminate or minimize the effects of this problem: full awareness and moral training of the scientists involved in the innovation process of higher education institutions; profit payment; creating a psychological climate that will affect the scientific process of self-realization; continuous training of employees involved in the innovation process of higher education institutions; the creation of conditions that will contribute to the manifestation of creative activity of scientists; provide greater confidence to young scientists, graduate students and undergraduates; providing moral and material encouragement of initiatives, experimentation and creativity of scientific and pedagogical staff; the allocation of free time for scientists to research and search activities and others. The data obtained can be used by the guidance of

  3. Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Yosuke, E-mail: cynagata@mail.ecc.u-tokyo.ac.jp; Ohashi, Kazuya; Wada, Eiji; Yuasa, Yuki; Shiozuka, Masataka; Nonomura, Yoshiaki; Matsuda, Ryoichi

    2014-08-01

    Skeletal muscle can regenerate repeatedly due to the presence of resident stem cells, called satellite cells. Because satellite cells are usually quiescent, they must be activated before participating in muscle regeneration in response to stimuli such as injury, overloading, and stretch. Although satellite cell activation is a crucial step in muscle regeneration, little is known of the molecular mechanisms controlling this process. Recent work showed that the bioactive lipid sphingosine-1-phosphate (S1P) plays crucial roles in the activation, proliferation, and differentiation of muscle satellite cells. We investigated the role of growth factors in S1P-mediated satellite cell activation. We found that epidermal growth factor (EGF) in combination with insulin induced proliferation of quiescent undifferentiated mouse myoblast C2C12 cells, which are also known as reserve cells, in serum-free conditions. Sphingosine kinase activity increased when reserve cells were stimulated with EGF. Treatment of reserve cells with the D-erythro-N,N-dimethylsphingosine, Sphingosine Kinase Inhibitor, or siRNA duplexes specific for sphingosine kinase 1, suppressed EGF-induced C2C12 activation. We also present the evidence showing the S1P receptor S1P2 is involved in EGF-induced reserve cell activation. Moreover, we demonstrated a combination of insulin and EGF promoted activation of satellite cells on single myofibers in a manner dependent on SPHK and S1P2. Taken together, our observations show that EGF-induced satellite cell activation is mediated by S1P and its receptor. - Highlights: • EGF in combination with insulin induces proliferation of quiescent C2C12 cells. • Sphingosine kinase activity increases when reserve cells are stimulated with EGF. • EGF-induced activation of reserve cells is dependent on sphingosine kinase and ERK. • The S1P receptor S1P2 is involved in EGF-induced reserve cell activation. • EGF-induced reserve cell activation is mediated by S1P and its

  4. Further evidence for a human B cell activating factor distinct from IL-4.

    Science.gov (United States)

    Diu, A; Février, M; Mollier, P; Charron, D; Banchereau, J; Reinherz, E L; Thèze, J

    1990-01-01

    Supernatants from activated human T cell clones were previously shown to contain B cell-activating factor (BCAF), an activity which results in polyclonal resting B cell stimulation. In the present study, we investigate the relationship between this activity and human interleukin-4 which was also shown to act on resting B cells. The supernatant of the T cell clone TT9 contains IL-4 but anti-IL-4 antiserum does not affect the response of B cells as measured by thymidine uptake or cell volume increase. Furthermore, IL-4 induces Fc epsilon-receptor (CD23) expression on 30% of unstimulated human B cells, whereas BCAF-containing supernatants from clone P2, that do not contain detectable amounts of IL-4, promote B cell proliferation without inducing CD23 expression. Our results therefore establish that IL-4 and BCAF are distinct activities and suggest that they trigger different activation pathways in human B cells. In addition, culture of B cells with T cell supernatants for 72 hr induces a three- to fourfold increase in the expression of HLA-DR, -DP, and -DQ antigens in 50% of B cells. The addition of inhibiting concentrations of anti-IFN-gamma, LT, or IL-4 antisera to the cultures does not change these results. Finally, 30% of B cells cultured with T cell supernatants leave the G1 phase of the cell cycle and 20% reach mitosis. Taken together, our findings further support the existence of a B cell-activating factor responsible for the activation of resting human B cells.

  5. Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif)

    Science.gov (United States)

    Ng, Mei Ying; Wang, Mei; Casey, Patrick J.; Gan, Yunn-Hwen; Hagen, Thilo

    2017-01-01

    Cycle inhibiting factors (Cifs) are virulence proteins secreted by the type III secretion system of some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Cif is known to function to deamidate Nedd8, leading to inhibition of Cullin E3 ubiquitin ligases (CRL) and consequently induction of cell cycle arrest. Here we show that Cif can function as a potent activator of MAPK/ERK signaling without significant activation of other signaling pathways downstream of receptor tyrosine kinases. Importantly, we found that the ability of Cif to activate ERK is dependent on its deamidase activity, but independent of Cullin E3 ligase inhibition. This suggests that apart from Nedd8, other cellular targets of Cif-dependent deamidation exist. We provide evidence that the mechanism involved in Cif-mediated ERK activation is dependent on recruitment of the Grb2-SOS1 complex to the plasma membrane. Further investigation revealed that Cif appears to modify the phosphorylation status of SOS1 in a region containing the CDC25-H and proline-rich domains. It is known that prolonged Cullin E3 ligase inhibition leads to cellular apoptosis. Therefore, we hypothesize that ERK activation is an important mechanism to counter the pro-apoptotic effects of Cif. Indeed, we show that Cif dependent ERK activation promotes phosphorylation of the proapoptotic protein Bim, thereby potentially conferring a pro-survival signal. In summary, we identified a novel deamidation-dependent mechanism of action of the B. pseudomallei virulence factor Cif/CHBP to activate MAPK/ERK signaling. Our study demonstrates that bacterial proteins such as Cif can serve as useful molecular tools to uncover novel aspects of mammalian signaling pathways. PMID:28166272

  6. Activation of MAPK/ERK signaling by Burkholderia pseudomallei cycle inhibiting factor (Cif).

    Science.gov (United States)

    Ng, Mei Ying; Wang, Mei; Casey, Patrick J; Gan, Yunn-Hwen; Hagen, Thilo

    2017-01-01

    Cycle inhibiting factors (Cifs) are virulence proteins secreted by the type III secretion system of some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Cif is known to function to deamidate Nedd8, leading to inhibition of Cullin E3 ubiquitin ligases (CRL) and consequently induction of cell cycle arrest. Here we show that Cif can function as a potent activator of MAPK/ERK signaling without significant activation of other signaling pathways downstream of receptor tyrosine kinases. Importantly, we found that the ability of Cif to activate ERK is dependent on its deamidase activity, but independent of Cullin E3 ligase inhibition. This suggests that apart from Nedd8, other cellular targets of Cif-dependent deamidation exist. We provide evidence that the mechanism involved in Cif-mediated ERK activation is dependent on recruitment of the Grb2-SOS1 complex to the plasma membrane. Further investigation revealed that Cif appears to modify the phosphorylation status of SOS1 in a region containing the CDC25-H and proline-rich domains. It is known that prolonged Cullin E3 ligase inhibition leads to cellular apoptosis. Therefore, we hypothesize that ERK activation is an important mechanism to counter the pro-apoptotic effects of Cif. Indeed, we show that Cif dependent ERK activation promotes phosphorylation of the proapoptotic protein Bim, thereby potentially conferring a pro-survival signal. In summary, we identified a novel deamidation-dependent mechanism of action of the B. pseudomallei virulence factor Cif/CHBP to activate MAPK/ERK signaling. Our study demonstrates that bacterial proteins such as Cif can serve as useful molecular tools to uncover novel aspects of mammalian signaling pathways.

  7. Signal Transducer and Activator of Transcription (STAT)-3 Activates Nuclear Factor (NF)-κB in Chronic Lymphocytic Leukemia Cells

    Science.gov (United States)

    Liu, Zhiming; Hazan-Halevy, Inbal; Harris, David M.; Li, Ping; Ferrajoli, Alessandra; Faderl, Stefan; Keating, Michael J.; Estrov, Zeev

    2014-01-01

    Nuclear factor (NF)-κB plays a major role in the pathogenesis of B-cell neoplasms. A broad array of mostly extracellular stimuli has been reported to activate NF-κB, to various degrees, in chronic lymphocytic leukemia (CLL) cells. Because CLL cells harbor high levels of unphosphorylated (U) signal transducer and activator of transcription (STAT)-3 protein and U-STAT3 was reported to activate NF-κB, we sought to determine whether U-STAT3 activates NF-κB in CLL. Using the electrophoretic mobility shift assay (EMSA) we studied peripheral blood low-density cells from 15 patients with CLL and found that CLL cell nuclear extracts from all the samples bound to an NF-κB DNA probe, suggesting that NF-κB is constitutively activated in CLL. Immunoprecipitation studies showed that STAT3 bound NF-κB p65, and confocal microscopy studies detected U-STAT3/NF-κB complexes in the nuclei of CLL cells, thereby confirming these findings. Furthermore, infection of CLL cells with retroviral STAT3-shRNA attenuated the binding of NF-κB to DNA, as assessed by EMSA, and downregulated mRNA levels of NF-κB-regulated genes, as assessed by quantitative polymerase chain reaction. Taken together, our data suggest that U-STAT3 binds to the NF-κB p50/p65 dimers and that the U-STAT3/NF-κB complexes bind to DNA and activate NF-κB-regulated genes in CLL cells. PMID:21364020

  8. The Guanine Nucleotide Exchange Factor ARNO mediates the activation of ARF and phospholipase D by insulin

    Science.gov (United States)

    Li, Hai-Sheng; Shome, Kuntala; Rojas, Raúl; Rizzo, Mark A; Vasudevan, Chandrasekaran; Fluharty, Eric; Santy, Lorraine C; Casanova, James E; Romero, Guillermo

    2003-01-01

    Background Phospholipase D (PLD) is involved in many signaling pathways. In most systems, the activity of PLD is primarily regulated by the members of the ADP-Ribosylation Factor (ARF) family of GTPases, but the mechanism of activation of PLD and ARF by extracellular signals has not been fully established. Here we tested the hypothesis that ARF-guanine nucleotide exchange factors (ARF-GEFs) of the cytohesin/ARNO family mediate the activation of ARF and PLD by insulin. Results Wild type ARNO transiently transfected in HIRcB cells was translocated to the plasma membrane in an insulin-dependent manner and promoted the translocation of ARF to the membranes. ARNO mutants: ΔCC-ARNO and CC-ARNO were partially translocated to the membranes while ΔPH-ARNO and PH-ARNO could not be translocated to the membranes. Sec7 domain mutants of ARNO did not facilitate the ARF translocation. Overexpression of wild type ARNO significantly increased insulin-stimulated PLD activity, and mutations in the Sec7 and PH domains, or deletion of the PH or CC domains inhibited the effects of insulin. Conclusions Small ARF-GEFs of the cytohesin/ARNO family mediate the activation of ARF and PLD by the insulin receptor. PMID:12969509

  9. Test-retest reliability of a questionnaire to assess physical environmental factors pertaining to physical activity

    Directory of Open Access Journals (Sweden)

    McGinn Aileen P

    2005-06-01

    Full Text Available Abstract Background Despite the documented benefits of physical activity, many adults do not obtain the recommended amounts. Barriers to physical activity occur at multiple levels, including at the individual, interpersonal, and environmental levels. Only until more recently has there been a concerted focus on how the physical environment might affect physical activity behavior. With this new area of study, self-report measures should be psychometrically tested before use in research studies. Therefore the objective of this study was to document the test-retest reliability of a questionnaire designed to assess physical environmental factors that might be associated with physical activity in a diverse adult population. Methods Test and retest surveys were conducted over the telephone with 106 African American and White women and men living in either Forsyth County, North Carolina or Jackson, Mississippi. Reliability of self-reported environmental factors across four domains (e.g., access to facilities and destinations, functionality and safety, aesthetics, natural environment was determined using intraclass correlation coefficients (ICC overall and separately by gender and race. Results Generally items displayed moderate and sometimes substantial reliability (ICC between 0.4 to 0.8, with a few differences by gender or race, across each of the domains. Conclusion This study provides some psychometric evidence for the use of many of these questions in studies examining the effect of self-reported physical environmental measures on physical activity behaviors, among African American and White women and men.

  10. The Guanine Nucleotide Exchange Factor ARNO mediates the activation of ARF and phospholipase D by insulin

    Directory of Open Access Journals (Sweden)

    Fluharty Eric

    2003-09-01

    Full Text Available Abstract Background Phospholipase D (PLD is involved in many signaling pathways. In most systems, the activity of PLD is primarily regulated by the members of the ADP-Ribosylation Factor (ARF family of GTPases, but the mechanism of activation of PLD and ARF by extracellular signals has not been fully established. Here we tested the hypothesis that ARF-guanine nucleotide exchange factors (ARF-GEFs of the cytohesin/ARNO family mediate the activation of ARF and PLD by insulin. Results Wild type ARNO transiently transfected in HIRcB cells was translocated to the plasma membrane in an insulin-dependent manner and promoted the translocation of ARF to the membranes. ARNO mutants: ΔCC-ARNO and CC-ARNO were partially translocated to the membranes while ΔPH-ARNO and PH-ARNO could not be translocated to the membranes. Sec7 domain mutants of ARNO did not facilitate the ARF translocation. Overexpression of wild type ARNO significantly increased insulin-stimulated PLD activity, and mutations in the Sec7 and PH domains, or deletion of the PH or CC domains inhibited the effects of insulin. Conclusions Small ARF-GEFs of the cytohesin/ARNO family mediate the activation of ARF and PLD by the insulin receptor.

  11. Activation of initiation factor 2 by ligands and mutations for rapid docking of ribosomal subunits.

    Science.gov (United States)

    Pavlov, Michael Y; Zorzet, Anna; Andersson, Dan I; Ehrenberg, Måns

    2011-01-19

    We previously identified mutations in the GTPase initiation factor 2 (IF2), located outside its tRNA-binding domain, compensating strongly (A-type) or weakly (B-type) for initiator tRNA formylation deficiency. We show here that rapid docking of 30S with 50S subunits in initiation of translation depends on switching 30S subunit-bound IF2 from its inactive to active form. Activation of wild-type IF2 requires GTP and formylated initiator tRNA (fMet-tRNA(i)). In contrast, extensive activation of A-type IF2 occurs with only GTP or with GDP and fMet-tRNA(i), implying a passive role for initiator tRNA as activator of IF2 in subunit docking. The theory of conditional switching of GTPases quantitatively accounts for all our experimental data. We find that GTP, GDP, fMet-tRNA(i) and A-type mutations multiplicatively increase the equilibrium ratio, K, between active and inactive forms of IF2 from a value of 4 × 10(-4) for wild-type apo-IF2 by factors of 300, 8, 80 and 20, respectively. Functional characterization of the A-type mutations provides keys to structural interpretation of conditional switching of IF2 and other multidomain GTPases.

  12. Activation of initiation factor 2 by ligands and mutations for rapid docking of ribosomal subunits

    Science.gov (United States)

    Pavlov, Michael Y; Zorzet, Anna; Andersson, Dan I; Ehrenberg, Måns

    2011-01-01

    We previously identified mutations in the GTPase initiation factor 2 (IF2), located outside its tRNA-binding domain, compensating strongly (A-type) or weakly (B-type) for initiator tRNA formylation deficiency. We show here that rapid docking of 30S with 50S subunits in initiation of translation depends on switching 30S subunit-bound IF2 from its inactive to active form. Activation of wild-type IF2 requires GTP and formylated initiator tRNA (fMet-tRNAi). In contrast, extensive activation of A-type IF2 occurs with only GTP or with GDP and fMet-tRNAi, implying a passive role for initiator tRNA as activator of IF2 in subunit docking. The theory of conditional switching of GTPases quantitatively accounts for all our experimental data. We find that GTP, GDP, fMet-tRNAi and A-type mutations multiplicatively increase the equilibrium ratio, K, between active and inactive forms of IF2 from a value of 4 × 10−4 for wild-type apo-IF2 by factors of 300, 8, 80 and 20, respectively. Functional characterization of the A-type mutations provides keys to structural interpretation of conditional switching of IF2 and other multidomain GTPases. PMID:21151095

  13. Immunohistochemical detection of active transforming growth factor-beta in situ using engineered tissue

    Science.gov (United States)

    Barcellos-Hoff, M. H.; Ehrhart, E. J.; Kalia, M.; Jirtle, R.; Flanders, K.; Tsang, M. L.; Chatterjee, A. (Principal Investigator)

    1995-01-01

    The biological activity of transforming growth factor-beta 1 (TGF-beta) is governed by dissociation from its latent complex. Immunohistochemical discrimination of active and latent TGF-beta could provide insight into TGF-beta activation in physiological and pathological processes. However, evaluation of immunoreactivity specificity in situ has been hindered by the lack of tissue in which TGF-beta status is known. To provide in situ analysis of antibodies to differentiate between these functional forms, we used xenografts of human tumor cells modified by transfection to overexpress latent TGF-beta or constitutively active TGF-beta. This comparison revealed that, whereas most antibodies did not differentiate between TGF-beta activation status, the immunoreactivity of some antibodies was activation dependent. Two widely used peptide antibodies to the amino-terminus of TGF-beta, LC(1-30) and CC(1-30) showed marked preferential immunoreactivity with active TGF-beta versus latent TGF-beta in cryosections. However, in formalin-fixed, paraffin-embedded tissue, discrimination of active TGF-beta by CC(1-30) was lost and immunoreactivity was distinctly extracellular, as previously reported for this antibody. Similar processing-dependent extracellular localization was found with a neutralizing antibody raised to recombinant TGF-beta. Antigen retrieval recovered cell-associated immunoreactivity of both antibodies. Two antibodies to peptides 78-109 showed mild to moderate preferential immunoreactivity with active TGF-beta only in paraffin sections. LC(1-30) was the only antibody tested that discriminated active from latent TGF-beta in both frozen and paraffin-embedded tissue. Thus, in situ discrimination of active versus latent TGF-beta depends on both the antibody and tissue preparation. We propose that tissues engineered to express a specific form of a given protein provide a physiological setting in which to evaluate antibody reactivity with specific functional forms of a

  14. Effect of charge at an amino acid of basic fibroblast growth factor on its mitogenic activity

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The amino acid at the 119th position of human basic fibroblast growth factor(hbFGF),lysine(K119),is a critical component for its mitogenic activity.However,little is known about the effects of the characteristics of this residue including charge on the mitogenic activity of hbFGF.Herein,this basic residue was replaced with neutral glutamine residue and acidic glutamic acid residue to construct mutants hbFGF~(K119Q) and hbFGF~(K119E),respectively.The mutants were produced by BL21(DE3)/pET3c expression sys...

  15. The epidermal growth factor receptor is a regulator of epidermal complement component expression and complement activation

    DEFF Research Database (Denmark)

    Abu-Humaidan, Anas H A; Ananthoju, Nageshwar; Mohanty, Tirthankar;

    2014-01-01

    The complement system is activated in response to tissue injury. During wound healing, complement activation seems beneficial in acute wounds but may be detrimental in chronic wounds. We found that the epidermal expression of many complement components was only increased to a minor extent in skin...... wounds in vivo and in cultured keratinocytes after exposure to supernatant from stimulated mononuclear cells. In contrast, the epidermal expression of complement components was downregulated in ex vivo injured skin lacking the stimulation from infiltrating inflammatory cells but with intact injury......-induced epidermal growth factor receptor (EGFR)-mediated growth factor response. In cultured primary keratinocytes, stimulation with the potent EGFR ligand, TGF-α, yielded a significant downregulation of complement component expression. Indeed, EGFR inhibition significantly enhanced the induction of complement...

  16. Transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in Bacillus subtilis.

    Science.gov (United States)

    Fedorova, Ksenia; Kayumov, Airat; Woyda, Kathrin; Ilinskaja, Olga; Forchhammer, Karl

    2013-05-02

    The Bacillus subtilis glutamine synthetase (GS) plays a dual role in cell metabolism by functioning as catalyst and regulator. GS catalyses the ATP-dependent synthesis of glutamine from glutamate and ammonium. Under nitrogen-rich conditions, GS becomes feedback-inhibited by high intracellular glutamine levels and then binds transcription factors GlnR and TnrA, which control the genes of nitrogen assimilation. While GS-bound TnrA is no longer able to interact with DNA, GlnR-DNA binding is shown to be stimulated by GS complex formation. In this paper we show a new physiological feature of the interaction between glutamine synthetase and TnrA. The transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in vivo and in vitro, while the GlnR protein does not affect the activity of the enzyme.

  17. The Covering Factor of Warm Dust in Weak Emission-Line Active Galactic Nuclei

    CERN Document Server

    Zhang, Xudong

    2016-01-01

    Weak emission-line active galactic nuclei (WLAGNs) are radio-quiet active galactic nuclei (AGNs) that have nearly featureless optical spectra. We investigate the ultraviolet to mid-infrared spectral energy distributions of 73 WLAGNs (0.4factor of warm dust of these 73 WLAGNs. No significant difference is indicated by a KS test between the covering factor of WLAGNs and normal AGNs in the common range of bolometric luminosity. The implication for several models of WLAGNs is discussed. The super-Eddington accretion is unlikely the dominant reason for the featureless spectrum of a WLAGN. The present results favor the evolution scenario, i.e., WLAGNs are in a special stage of AGNs.

  18. Transcription activation of a UV-inducible Clostridium perfringens bacteriocin gene by a novel sigma factor.

    Science.gov (United States)

    Dupuy, Bruno; Mani, Nagraj; Katayama, Seiichi; Sonenshein, Abraham L

    2005-02-01

    Expression of the plasmid-encoded Clostridium perfringens gene for bacteriocin BCN5 was shown to depend in vivo and in vitro on the activity of UviA protein. UviA, also plasmid-encoded, proved to be an RNA polymerase sigma factor and was also partly autoregulatory. The uviA gene has two promoters; one provided a UviA-independent, basal level of gene expression while the stronger, UviA-dependent promoter was only utilized after the cell experienced DNA damage. As a result, BCN5 synthesis is induced by treatment with UV light or mitomycin C. UviA is related to a special class of sigma factors found to date only in Clostridium species and responsible for activating transcription of toxin genes in Clostridium difficile, Clostridium tetani, and Clostridium botulinum.

  19. Factors predicting health behaviors among Army Reserve, active duty Army, and civilian hospital employees.

    Science.gov (United States)

    Wynd, Christine A; Ryan-Wenger, Nancy A

    2004-12-01

    This study identified health-risk and health-promoting behaviors in military and civilian personnel employed in hospitals. Intrinsic self-motivation and extrinsic organizational workplace factors were examined as predictors of health behaviors. Because reservists represent a blend of military and civilian lifestyles, descriptive analyses focused on comparing Army Reserve personnel (n = 199) with active duty Army (n = 218) and civilian employees (n = 193), for a total sample of 610. Self-motivation and social support were significant factors contributing to the adoption of health-promoting behaviors; however, organizational workplace cultures were inconsistent predictors of health among the three groups. Only the active Army subgroup identified a hierarchical culture as having an influence on health promotion, possibly because of the Army's mandatory physical fitness and weight control standards. Social support and self-motivation are essential to promoting health among employees, thus hospital commanders and chief executive officers should encourage strategies that enhance and reward these behaviors.

  20. Effect of individual dietary fatty acids on postprandial activation of blood coagulation factor VII and fibrinolysis in healthy young men

    DEFF Research Database (Denmark)

    Tholstrup, T.; Miller, G.J.; Bysted, Anette

    2003-01-01

    Background: Hypertriglyceridemia may represent a procoagulant state involving disturbances to the hemostatic system. Plasminogen activator inhibitor type 1 (PAI-1) is increased in the presence of hypertriglyceridemia. Free fatty acids (FFAs) in plasma may promote factor VII (FVII) activation...

  1. Influence of Socioeconomic Factors on Daily Life Activities and Quality of Life of Thai Elderly.

    Science.gov (United States)

    Somrongthong, Ratana; Wongchalee, Sunanta; Ramakrishnan, Chandrika; Hongthong, Donnapa; Yodmai, Korravarn; Wongtongkam, Nualnong

    2017-04-13

    The increasing number of older people is a significant issue in Thailand, resulted in growing demands of health and social welfare services. The study aim was to explore the influence of socioeconomic factors on activities of daily living and quality of life of Thai seniors. Using randomised cluster sampling, one province was sampled from each of the Central, North, Northeast and South regions, then one subdistrict sampled in each province, and a household survey used to identify the sample of 1678 seniors aged 60 years and over. The Mann-Whitney U-test and binary logistic regression were used to compare and determine the association of socioeconomic variables on quality of life and activities of daily living. The findings showed that sociodemographic and socioeconomic factors were significantly related to functional capacity of daily living. Education levels were strongly associated with daily life activities, with 3.55 adjusted ORs for respondents with secondary school education. Gender was important, with females comprising 61% of dependent respondents but only 47% of independent respondents. Seniors with low incomes were more likely to be anxious in the past, present and future and less likely to accept death in the late stage, with 1.40 Adjusted ORs (95%CI: 1.02-1.92), and 0.72 (95%CI: 0.53-0.98), respectively. However, they were more likely to engage in social activities. While socioeconomic factors strongly indicated the functional capacity to live independently, a good quality of life also required other factors leading to happiness and life satisfaction.

  2. Influence of socioeconomic factors on daily life activities and quality of life of Thai elderly

    Directory of Open Access Journals (Sweden)

    Ratana Somrongthong

    2017-06-01

    Full Text Available Background: The increasing number of older people is a significant issue in Thailand, resulted in growing demands of health and social welfare services. The study aim was to explore the influence of socioeconomic factors on activities of daily living and quality of life of Thai seniors. Design and methods: Using randomised cluster sampling, one province was sampled from each of the Central, North, Northeast and South regions, then one subdistrict sampled in each province, and a household survey used to identify the sample of 1678 seniors aged 60 years and over. The Mann-Whitney U-test and binary logistic regression were used to compare and determine the association of socioeconomic variables on quality of life and activities of daily living. Results: The findings showed that sociodemographic and socioeconomic factors were significantly related to functional capacity of daily living. Education levels were strongly associated with daily life activities, with 3.55 adjusted ORs for respondents with secondary school education. Gender was important, with females comprising 61% of dependent respondents but only 47% of independent respondents. Seniors with low incomes were more likely to be anxious in the past, present and future and less likely to accept death in the late stage, with 1.40 Adjusted ORs (95%CI: 1.02-1.92, and 0.72 (95%CI: 0.53-0.98, respectively. However, they were more likely to engage in social activities. Conclusions: While socioeconomic factors strongly indicated the functional capacity to live independently, a good quality of life also required other factors leading to happiness and life satisfaction.

  3. Cardiovascular risk factors and physical activity among university students in Somaliland.

    Science.gov (United States)

    Ali, Mahdi; Yusuf, Hassan Ismail; Stahmer, Jens; Rahlenbeck, Sibylle I

    2015-04-01

    Physical inactivity is a well-known risk factor for the development of cardiovascular diseases and counts as fourth leading cause of death worldwide. The study aimed to elucidate to what extent cardiovascular risk factors exist in university students in Somaliland. In a cross-sectional survey, self-administered questionnaires were used to elucidate existence of cardiovascular risk factors in 173 university students (117 male, 56 female) in Hargeisa, Somaliland. Information elucidated included socio-economic and demographic data in addition to questions on coffee intake, on physical activity behavior, type of sport/activity and intensity and duration. Height and weight were taken, as was blood pressure (BP). Median age was 23 years in male and 20 years in female students. Mean BMI was 19.7 in male and 21.8 in female students. The prevalence rates of elevated BP and overweight (BMI ≥ 25) in female and male students were, 0 versus 9 and 14 versus 7 %, respectively. Coffee consumption was reported by 39 % of students. None of the female students reported smoking cigarettes, while 5.1 % of the male students did. Physical inactivity was reported by 52 % of the female students and 27 % of the male students (p = 0.01). Overall, male students reported a higher degree and intensity of physical activity. The prevalence of cardiovascular risk factors is low in female and male university students in Somaliland. However, the results demonstrate a high degree of physical inactivity and overweight might become a problem in the future. This issue should be addressed by increasing the motivation and opportunities for physical activity in students.

  4. [Correlation analysis between meteorological factors, biomass, and active components of Salvia miltiorrhiza in different climatic zones].

    Science.gov (United States)

    Zhang, Chen-lu; Liang, Zong-suo; Guo, Hong-bo; Liu, Jing-ling; Liu, Yan; Liu, Feng-hua; Wei, Lang-zhu

    2015-02-01

    In this study, the growth and accumulation of active components of Salvia miltiorrhiza in twenty two experimental sites which crossing through three typical climate zones. The S. miltiorrhiza seedlings with the same genotype were planted in each site in spring, which were cultivated in fields with uniform management during their growing seasons till to harvest. The diterpene ketones (dihydrotanshinone, cryptotanshinone, tanshinone I and tanshinone II(A)) in S. miltiorrhiza root samples were determined by using high-performance liquid chromatography (HPLC) method. The biomass of root (root length, number of root branches, root width and dry weight) was also measured. The results showed that tanshinone II(A) in all samples of each site were higher than the standards required by China Pharmacopoeia. It has been found there is a relationship between root shape and climate change. The correlation analysis between active components and meteorological factors showed that the accumulation of tanshinones were effected by such meteorological factors as average relative humidity from April to October > average vapor pressure from April to October > average temperature difference day and night from April to October > annual average temperature and so on. The correlation analysis between root biomass and meteorological factors exhibited that root shape and accumulation of dry matter were affected by those factors, such as average annual aboveground (0-20 cm) temperature from April to October > annual average temperature > average vapor pressure from April to October > annual active accumulated temperature > annual average temperature > average vapor pressure from April to October. The accumulation of tanshinones and biomass was increased with the decrease of latitude. At the same time, the dry matter and diameter of root decreased if altitude rises. In addition, S. miltiorrhiza required sunlight is not sophisticated, when compared with humid and temperature. To sum up, S

  5. A Minimal Rac Activation Domain in the Unconventional Guanine Nucleotide Exchange Factor Dock180†

    OpenAIRE

    Xin WU; Ramachandran, Sekar; Cerione, Richard A.; Erickson, Jon W.

    2011-01-01

    Guanine nucleotide exchange factors (GEFs) activate Rho GTPases by catalyzing the exchange of bound GDP for GTP, thereby resulting in downstream effector recognition. Two metazoan families of GEFs have been described: Dbl-GEF family members that share conserved Dbl homology (DH) and Pleckstrin homology (PH) domains and the more recently described Dock180 family members that share little sequence homology with the Dbl family and are characterized by conserved Dock homology regions 1 and 2 (DHR...

  6. Knee hemarthrosis after arthroscopic surgery in an athlete with low factor XIII activity

    OpenAIRE

    Tsujii Akira; Tanaka Yoshinari; Yonetani Yasukazu; Shiozaki Yoshiki; Tomiyama Yoshiaki; Horibe Shuji

    2012-01-01

    Abstract We report a thirteen-year-old tennis player with knee h